Trial Outcomes & Findings for PANGEA-IMBBP: Personalized Antibodies for Gastro-Esophageal Adenocarcinoma - A 1st Pilot Metastatic Trial of Biologics Beyond Progression (NCT NCT02213289)

NCT ID: NCT02213289

Last Updated: 2021-04-08

Results Overview

Time from enrollment to death from any cause.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

80 participants

Primary outcome timeframe

Up to 60 months

Results posted on

2021-04-08

Participant Flow

Participant milestones

Participant milestones
Measure	ITT-PTS: Personalized Treatment Strategy For patients with monoclonal antibiodies available, initial therapy was tailored based on biomarker profile as follows: Immuno-oncology patients including PD-L1 IHC combined positivity score \>10, high microsatellite instability, tumor mutation burden \>15 mutations/megabase, and/or Epstein-Barr virus positive received standard cytotherapy plus Nivolumab. HER2 amplified patients received standard cytotherapy plus Trastuzumab. EGFR amplified patients received standard cytotherapy plus ABT-806 FGFR2 amplified patients received standard cytotherapy plus Bemarituzumab. MAPK/PIK3CA aberrant patients received standard cytotherapy plus Ramucirumab. EGFR expressing patients received standard cytotherapy plus ABT 806. All negative patients received standard cytotherapy plus Ramucirumab. Of note, while the protocol section describes these tailored therapies, the efficacy evaluation was based on pooling these treatments into a combined "personalized treatment strategy" group and comparing with historical controls. Therefore this "arm" includes all such patients with monoclonal antibodies available.	Non-ITT: Standard Therapy For patients without monoclonal antibodies available. These patients received standard cytotherapy consisting of FOLFOX (First Line) +FOLFIRI (Second Line) +FOLTAX (Third Line) Of note, this arm includes patients without monoclonal antibodies available, for whom no personalized treatment strategy was available. The intent of the protocol was NOT to compare this arm with arm 1.
Overall Study STARTED	68	12
Overall Study Immuno-oncology	5	0
Overall Study HER2 Amplified	16	0
Overall Study EGFR Amplified	8	0
Overall Study FGFR2 Amplified	1	0
Overall Study MAPK/PIK3CA Aberrant	20	0
Overall Study EGFR Expressing	9	0
Overall Study All Negative	9	0
Overall Study Other (Non-ITT)	0	12
Overall Study COMPLETED	68	12
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

PANGEA-IMBBP: Personalized Antibodies for Gastro-Esophageal Adenocarcinoma - A 1st Pilot Metastatic Trial of Biologics Beyond Progression

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ITT-PTS: Personalized Treatment Strategy n=68 Participants For patients with monclonal antibiodies available, initial therapy was tailored based on biomarker profile as follows: Immuno-oncology patients including PD-L1 IHC combined positivity score \>10, high microsatellite instability, tumor mutation burden \>15 mutations/megabase, and/or Epstein-Barr virus positive patients received standard cytoptherapy plus Nivolumab HER2 amplified patients received standard cytotherapy plus Trastuzumab EGFR amplified patients received standard cytotherapy plus ABT-806 FGFR2 amplified patients received standard cytotherapy plus Bemarituzumab MAPK/PIK3CA aberrant patients received standard cytotherapy plus Ramucirumab. EGFR expressing patients received standard cytotherapy plus ABT 806. All negative patients received standard cytotherapy plus Ramucirumab.	Non-ITT: Standard Therapy n=12 Participants For patients without monoclonal antibodies available, therapy was standard cytotherapy consisting of FOLFOX (First Line) +FOLFIRI (Second Line) +FOLTAX (Third Line)	Total n=80 Participants Total of all reporting groups
Age, Continuous	61 years n=99 Participants	61 years n=107 Participants	61 years n=206 Participants
Sex: Female, Male Female	15 Participants n=99 Participants	1 Participants n=107 Participants	16 Participants n=206 Participants
Sex: Female, Male Male	53 Participants n=99 Participants	11 Participants n=107 Participants	64 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	2 Participants n=99 Participants	0 Participants n=107 Participants	2 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	7 Participants n=99 Participants	0 Participants n=107 Participants	7 Participants n=206 Participants
Race (NIH/OMB) White	57 Participants n=99 Participants	11 Participants n=107 Participants	68 Participants n=206 Participants
Race (NIH/OMB) More than one race	2 Participants n=99 Participants	1 Participants n=107 Participants	3 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Region of Enrollment United States	68 participants n=99 Participants	12 participants n=107 Participants	80 participants n=206 Participants

PRIMARY outcome

Timeframe: Up to 60 months

Time from enrollment to death from any cause.

Outcome measures

Outcome measures
Measure	ITT-PTS: Personalized Treatment Strategy n=68 Participants For patients with monclonal antibiodies available, initial therapy was tailored based on biomarker profile as follows: Immuno-oncology patients including PD-L1 IHC combined positivity score \>10, high microsatellite instability, tumor mutation burden \>15 mutations/megabase, and/or Epstein-Barr virus positive received standard cytotherapy plus Nivolumab. HER2 amplified patients received standard cytotherapy plus received Trastuzumab EGFR amplified patients received standard cytotherapy plus ABT-806 FGFR2 amplified patients received standard cytotherapy plus Bemarituzumab. MAPK/PIK3CA aberrant patients received standard cytotherapy plus Ramucirumab. EGFR expressing patients received standard cytotherapy plus ABT 806. All negative patients received standard cytotherapy plus Ramucirumab.	Non-ITT: Standard Therapy n=12 Participants For patients without monoclonal antibodies available. These patients received standard cytotherapy consisting of FOLFOX (First Line) +FOLFIRI (Second Line) +FOLTAX (Third Line)
Overall Survival	15.7 months Interval 13.4 to 17.7	9.0 months Interval 4.6 to 20.3

SECONDARY outcome

Timeframe: 1 Month

Population: Unit of analysis is the biopsy. Each patient had two biopsies, one of the primary tumor and one of a metastatic site.

Number of biopsies leading to an adverse event of the total undergoing baseline biopsies of a primary and metastatic disease site (liver, lung, lymph node, peritoneum/carcinomatosis).

Outcome measures

Outcome measures
Measure	ITT-PTS: Personalized Treatment Strategy n=136 Biopsies For patients with monclonal antibiodies available, initial therapy was tailored based on biomarker profile as follows: Immuno-oncology patients including PD-L1 IHC combined positivity score \>10, high microsatellite instability, tumor mutation burden \>15 mutations/megabase, and/or Epstein-Barr virus positive received standard cytotherapy plus Nivolumab. HER2 amplified patients received standard cytotherapy plus received Trastuzumab EGFR amplified patients received standard cytotherapy plus ABT-806 FGFR2 amplified patients received standard cytotherapy plus Bemarituzumab. MAPK/PIK3CA aberrant patients received standard cytotherapy plus Ramucirumab. EGFR expressing patients received standard cytotherapy plus ABT 806. All negative patients received standard cytotherapy plus Ramucirumab.	Non-ITT: Standard Therapy n=24 Biopsies For patients without monoclonal antibodies available. These patients received standard cytotherapy consisting of FOLFOX (First Line) +FOLFIRI (Second Line) +FOLTAX (Third Line)
Number of Biopsies Leading to an Adverse Event	1 biopsies	0 biopsies

SECONDARY outcome

Timeframe: Up to 1 month

Population: Unit of analysis is the biopsy. Two biopsies were performed per patient, one of the primary tumor and one from a metastatic site.

Completion of biopsies with successful assignment per the treatment algorithm. Biomarker profile assays included next generation sequencing (NGS). EGFR expression was performed by selected-reaction-monitoring mass spectrometry (SRM-MS).

Outcome measures

Outcome measures
Measure	ITT-PTS: Personalized Treatment Strategy n=136 Biopsies For patients with monclonal antibiodies available, initial therapy was tailored based on biomarker profile as follows: Immuno-oncology patients including PD-L1 IHC combined positivity score \>10, high microsatellite instability, tumor mutation burden \>15 mutations/megabase, and/or Epstein-Barr virus positive received standard cytotherapy plus Nivolumab. HER2 amplified patients received standard cytotherapy plus received Trastuzumab EGFR amplified patients received standard cytotherapy plus ABT-806 FGFR2 amplified patients received standard cytotherapy plus Bemarituzumab. MAPK/PIK3CA aberrant patients received standard cytotherapy plus Ramucirumab. EGFR expressing patients received standard cytotherapy plus ABT 806. All negative patients received standard cytotherapy plus Ramucirumab.	Non-ITT: Standard Therapy n=24 Biopsies For patients without monoclonal antibodies available. These patients received standard cytotherapy consisting of FOLFOX (First Line) +FOLFIRI (Second Line) +FOLTAX (Third Line)
Completion of Biopsy and Successful, Molecularly-based Treatment Assignment	134 biopsies	23 biopsies

SECONDARY outcome

Timeframe: Up to 60 Months

Population: This includes subset of patients administered second-line treatment

Number of participants with adverse events from serial biopsies of progressing metastatic disease sites (liver, lung, lymph node, peritoneum/carcinomatosis)

Outcome measures

Outcome measures
Measure	ITT-PTS: Personalized Treatment Strategy n=61 Participants For patients with monclonal antibiodies available, initial therapy was tailored based on biomarker profile as follows: Immuno-oncology patients including PD-L1 IHC combined positivity score \>10, high microsatellite instability, tumor mutation burden \>15 mutations/megabase, and/or Epstein-Barr virus positive received standard cytotherapy plus Nivolumab. HER2 amplified patients received standard cytotherapy plus received Trastuzumab EGFR amplified patients received standard cytotherapy plus ABT-806 FGFR2 amplified patients received standard cytotherapy plus Bemarituzumab. MAPK/PIK3CA aberrant patients received standard cytotherapy plus Ramucirumab. EGFR expressing patients received standard cytotherapy plus ABT 806. All negative patients received standard cytotherapy plus Ramucirumab.	Non-ITT: Standard Therapy n=11 Participants For patients without monoclonal antibodies available. These patients received standard cytotherapy consisting of FOLFOX (First Line) +FOLFIRI (Second Line) +FOLTAX (Third Line)
Adverse Event From Serial Biopsy for Second-line Treatment	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 60 months

Population: This includes subset of patients administered second-line treatment

Completion of biopsy with successful treatment assignment per the treatment algorithm. Biomarker profile assays included next generation sequencing (NGS). EGFR expression was performed by selected-reaction-monitoring mass spectrometry (SRM-MS).

Outcome measures

Outcome measures
Measure	ITT-PTS: Personalized Treatment Strategy n=61 Participants For patients with monclonal antibiodies available, initial therapy was tailored based on biomarker profile as follows: Immuno-oncology patients including PD-L1 IHC combined positivity score \>10, high microsatellite instability, tumor mutation burden \>15 mutations/megabase, and/or Epstein-Barr virus positive received standard cytotherapy plus Nivolumab. HER2 amplified patients received standard cytotherapy plus received Trastuzumab EGFR amplified patients received standard cytotherapy plus ABT-806 FGFR2 amplified patients received standard cytotherapy plus Bemarituzumab. MAPK/PIK3CA aberrant patients received standard cytotherapy plus Ramucirumab. EGFR expressing patients received standard cytotherapy plus ABT 806. All negative patients received standard cytotherapy plus Ramucirumab.	Non-ITT: Standard Therapy n=11 Participants For patients without monoclonal antibodies available. These patients received standard cytotherapy consisting of FOLFOX (First Line) +FOLFIRI (Second Line) +FOLTAX (Third Line)
Completion of Serial Biopsy for Second Line Therapy and Successful, Molecularly-based Treatment Assignment	51 Participants	9 Participants

SECONDARY outcome

Timeframe: Up to 60 months

Population: This includes subset of patients administered third-line treatment

Number of participants with adverse events from serial biopsies of progressing metastatic disease sites (liver, lung, lymph node, peritoneum/carcinomatosis)

Outcome measures

Outcome measures
Measure	ITT-PTS: Personalized Treatment Strategy n=25 Participants For patients with monclonal antibiodies available, initial therapy was tailored based on biomarker profile as follows: Immuno-oncology patients including PD-L1 IHC combined positivity score \>10, high microsatellite instability, tumor mutation burden \>15 mutations/megabase, and/or Epstein-Barr virus positive received standard cytotherapy plus Nivolumab. HER2 amplified patients received standard cytotherapy plus received Trastuzumab EGFR amplified patients received standard cytotherapy plus ABT-806 FGFR2 amplified patients received standard cytotherapy plus Bemarituzumab. MAPK/PIK3CA aberrant patients received standard cytotherapy plus Ramucirumab. EGFR expressing patients received standard cytotherapy plus ABT 806. All negative patients received standard cytotherapy plus Ramucirumab.	Non-ITT: Standard Therapy n=3 Participants For patients without monoclonal antibodies available. These patients received standard cytotherapy consisting of FOLFOX (First Line) +FOLFIRI (Second Line) +FOLTAX (Third Line)
Adverse Event From Serial Biopsy for Third-line Treatment	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 60 months

Population: This includes subset of patients administered third-line treatment

Outcome measures

Outcome measures
Measure	ITT-PTS: Personalized Treatment Strategy n=25 Participants For patients with monclonal antibiodies available, initial therapy was tailored based on biomarker profile as follows: Immuno-oncology patients including PD-L1 IHC combined positivity score \>10, high microsatellite instability, tumor mutation burden \>15 mutations/megabase, and/or Epstein-Barr virus positive received standard cytotherapy plus Nivolumab. HER2 amplified patients received standard cytotherapy plus received Trastuzumab EGFR amplified patients received standard cytotherapy plus ABT-806 FGFR2 amplified patients received standard cytotherapy plus Bemarituzumab. MAPK/PIK3CA aberrant patients received standard cytotherapy plus Ramucirumab. EGFR expressing patients received standard cytotherapy plus ABT 806. All negative patients received standard cytotherapy plus Ramucirumab.	Non-ITT: Standard Therapy n=3 Participants For patients without monoclonal antibodies available. These patients received standard cytotherapy consisting of FOLFOX (First Line) +FOLFIRI (Second Line) +FOLTAX (Third Line)
Completion of Serial Biopsy for Third Line Therapy and Successful, Molecularly-based Treatment Assignment	21 Participants	3 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 60 Months

Time from enrollment to progression or death during first-line treatment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Outcome measures

Outcome measures
Measure	ITT-PTS: Personalized Treatment Strategy n=68 Participants For patients with monclonal antibiodies available, initial therapy was tailored based on biomarker profile as follows: Immuno-oncology patients including PD-L1 IHC combined positivity score \>10, high microsatellite instability, tumor mutation burden \>15 mutations/megabase, and/or Epstein-Barr virus positive received standard cytotherapy plus Nivolumab. HER2 amplified patients received standard cytotherapy plus received Trastuzumab EGFR amplified patients received standard cytotherapy plus ABT-806 FGFR2 amplified patients received standard cytotherapy plus Bemarituzumab. MAPK/PIK3CA aberrant patients received standard cytotherapy plus Ramucirumab. EGFR expressing patients received standard cytotherapy plus ABT 806. All negative patients received standard cytotherapy plus Ramucirumab.	Non-ITT: Standard Therapy n=12 Participants For patients without monoclonal antibodies available. These patients received standard cytotherapy consisting of FOLFOX (First Line) +FOLFIRI (Second Line) +FOLTAX (Third Line)
First-line Progression-free Survival	8.2 months Interval 7.3 to 9.6	6.7 months Interval 2.9 to 10.6

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 6 months

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Outcome measures

Outcome measures
Measure	ITT-PTS: Personalized Treatment Strategy n=54 Participants For patients with monclonal antibiodies available, initial therapy was tailored based on biomarker profile as follows: Immuno-oncology patients including PD-L1 IHC combined positivity score \>10, high microsatellite instability, tumor mutation burden \>15 mutations/megabase, and/or Epstein-Barr virus positive received standard cytotherapy plus Nivolumab. HER2 amplified patients received standard cytotherapy plus received Trastuzumab EGFR amplified patients received standard cytotherapy plus ABT-806 FGFR2 amplified patients received standard cytotherapy plus Bemarituzumab. MAPK/PIK3CA aberrant patients received standard cytotherapy plus Ramucirumab. EGFR expressing patients received standard cytotherapy plus ABT 806. All negative patients received standard cytotherapy plus Ramucirumab.	Non-ITT: Standard Therapy n=10 Participants For patients without monoclonal antibodies available. These patients received standard cytotherapy consisting of FOLFOX (First Line) +FOLFIRI (Second Line) +FOLTAX (Third Line)
Objective Response to First Line Therapy	40 Participants	4 Participants

Adverse Events

ITT-PTS: Personalized Treatment Strategy

Serious events: 29 serious events

Other events: 68 other events

Deaths: 56 deaths

Non-ITT: Standard Therapy

Serious events: 8 serious events

Other events: 12 other events

Deaths: 11 deaths

Serious adverse events

Other adverse events

Additional Information

Daniel Catenacci, MD

University of Chicago

Phone: 2-1000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	ITT-PTS: Personalized Treatment Strategy n=68 participants at risk For patients with monclonal antibiodies available, initial therapy was tailored based on biomarker profile as follows: Immuno-oncology patients including PD-L1 IHC combined positivity score \>10, high microsatellite instability, tumor mutation burden \>15 mutations/megabase, and/or Epstein-Barr virus positive received standard cytotherapy plus Nivolumab. HER2 amplified patients received standard cytotherapy plus Trastuzumab. EGFR amplified patients received standard cytotherapy plus ABT-806.. FGFR2 amplified patients received standard cytotherapy plus Bemarituzumab. MAPK/PIK3CA aberrant patients received standard cytotherapy plus Ramucirumab. EGFR expressing patients received standard cytotherapy plus ABT 806. All negative patients received standard cytotherapy plus Ramucirumab.	Non-ITT: Standard Therapy n=12 participants at risk For patients without monoclonal antibodies available.These patients received standard cytotherapy consisting of FOLFOX (First Line) +FOLFIRI (Second Line) +FOLTAX (Third Line)
Gastrointestinal disorders Abdominal pain	1.5% 1/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	0.00% 0/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Investigations Alanine aminotransferase increased	1.5% 1/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	0.00% 0/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Blood and lymphatic system disorders Anemia	2.9% 2/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	0.00% 0/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Gastrointestinal disorders Ascites	1.5% 1/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	8.3% 1/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Investigations Aspartate aminotransferase increased	1.5% 1/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	0.00% 0/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Respiratory, thoracic and mediastinal disorders Aspiration	5.9% 4/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	0.00% 0/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	8.3% 1/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other	1.5% 1/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	0.00% 0/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Investigations Blood bilirubin increased	0.00% 0/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	8.3% 1/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Infections and infestations Catheter related infection	1.5% 1/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	0.00% 0/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Psychiatric disorders Confusion	0.00% 0/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	8.3% 1/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	8.3% 1/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
General disorders Death NOS	1.5% 1/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	8.3% 1/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Metabolism and nutrition disorders Dehydration	1.5% 1/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	0.00% 0/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Psychiatric disorders Delirium	1.5% 1/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	0.00% 0/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Gastrointestinal disorders Diarrhea	2.9% 2/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	0.00% 0/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Gastrointestinal disorders Dysphagia	5.9% 4/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	0.00% 0/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Respiratory, thoracic and mediastinal disorders Dyspnea	1.5% 1/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	16.7% 2/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
General disorders Edema limbs	0.00% 0/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	8.3% 1/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Gastrointestinal disorders Esophageal obstruction	1.5% 1/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	0.00% 0/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Gastrointestinal disorders Esophageal perforation	1.5% 1/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	0.00% 0/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Gastrointestinal disorders Esophagitis	1.5% 1/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	0.00% 0/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Injury, poisoning and procedural complications Fall	1.5% 1/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	0.00% 0/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
General disorders Fatigue	1.5% 1/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	0.00% 0/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Blood and lymphatic system disorders Febrile neutropenia	1.5% 1/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	0.00% 0/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
General disorders Fever	2.9% 2/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	8.3% 1/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Gastrointestinal disorders Gastrointestinal disorders - Other	1.5% 1/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	0.00% 0/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Gastrointestinal disorders Gastroparesis	1.5% 1/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	0.00% 0/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Metabolism and nutrition disorders Hypokalemia	1.5% 1/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	0.00% 0/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Gastrointestinal disorders Nausea	2.9% 2/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	16.7% 2/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
General disorders Non-cardiac chest pain	2.9% 2/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	8.3% 1/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Infections and infestations Pelvic infection	1.5% 1/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	0.00% 0/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Infections and infestations Phlebitis infective	1.5% 1/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	0.00% 0/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Investigations Platelet count decreased	1.5% 1/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	0.00% 0/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.5% 1/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	0.00% 0/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Renal and urinary disorders Renal and urinary disorders - Other	1.5% 1/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	0.00% 0/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Nervous system disorders Seizure	1.5% 1/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	0.00% 0/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Infections and infestations Sepsis	7.4% 5/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	8.3% 1/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Gastrointestinal disorders Small intestinal obstruction	1.5% 1/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	0.00% 0/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Nervous system disorders Stroke	2.9% 2/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	0.00% 0/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.

Other adverse events
Measure	ITT-PTS: Personalized Treatment Strategy n=68 participants at risk For patients with monclonal antibiodies available, initial therapy was tailored based on biomarker profile as follows: Immuno-oncology patients including PD-L1 IHC combined positivity score \>10, high microsatellite instability, tumor mutation burden \>15 mutations/megabase, and/or Epstein-Barr virus positive received standard cytotherapy plus Nivolumab. HER2 amplified patients received standard cytotherapy plus Trastuzumab. EGFR amplified patients received standard cytotherapy plus ABT-806.. FGFR2 amplified patients received standard cytotherapy plus Bemarituzumab. MAPK/PIK3CA aberrant patients received standard cytotherapy plus Ramucirumab. EGFR expressing patients received standard cytotherapy plus ABT 806. All negative patients received standard cytotherapy plus Ramucirumab.	Non-ITT: Standard Therapy n=12 participants at risk For patients without monoclonal antibodies available.These patients received standard cytotherapy consisting of FOLFOX (First Line) +FOLFIRI (Second Line) +FOLTAX (Third Line)
Gastrointestinal disorders Abdominal distenstion	5.9% 4/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	8.3% 1/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Gastrointestinal disorders Abdominal pain	54.4% 37/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	58.3% 7/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Investigations Alanine aminotransferase increased	4.4% 3/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	25.0% 3/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Skin and subcutaneous tissue disorders Alopecia	10.3% 7/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	8.3% 1/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Blood and lymphatic system disorders Anemia	29.4% 20/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	8.3% 1/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Metabolism and nutrition disorders Anorexia	60.3% 41/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	58.3% 7/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Musculoskeletal and connective tissue disorders Arthralgia	7.4% 5/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	0.00% 0/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Psychiatric disorders Anxiety	0.00% 0/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	8.3% 1/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Gastrointestinal disorders Ascites	11.8% 8/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	16.7% 2/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Investigations Aspartate aminotransferase increased	5.9% 4/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	25.0% 3/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Respiratory, thoracic and mediastinal disorders Aspiration	1.5% 1/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	8.3% 1/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Musculoskeletal and connective tissue disorders Back pain	29.4% 20/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	8.3% 1/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Gastrointestinal disorders Bloating	10.3% 7/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	16.7% 2/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Investigations Blood bilirubin increased	10.3% 7/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	8.3% 1/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Eye disorders Blurred vision	1.5% 1/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	8.3% 1/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Injury, poisoning and procedural complications Bruising	2.9% 2/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	8.3% 1/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Congenital, familial and genetic disorders Chest pain - cardiac	4.4% 3/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	8.3% 1/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
General disorders Chills	8.8% 6/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	0.00% 0/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Gastrointestinal disorders Colitis	7.4% 5/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	8.3% 1/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Gastrointestinal disorders Constipation	47.1% 32/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	33.3% 4/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Respiratory, thoracic and mediastinal disorders Cough	23.5% 16/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	41.7% 5/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Gastrointestinal disorders Diarrhea	63.2% 43/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	41.7% 5/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Nervous system disorders Dizzines	20.6% 14/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	8.3% 1/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Skin and subcutaneous tissue disorders Dry skin	5.9% 4/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	8.3% 1/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Nervous system disorders Dysgeusia	38.2% 26/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	33.3% 4/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Gastrointestinal disorders Dyspepsia/heartburn	7.4% 5/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	8.3% 1/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Gastrointestinal disorders Dysphagia, esophagitis, odynophagia	39.7% 27/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	41.7% 5/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Respiratory, thoracic and mediastinal disorders Dyspnea	25.0% 17/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	16.7% 2/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
General disorders Edema limbs	29.4% 20/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	33.3% 4/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Respiratory, thoracic and mediastinal disorders Epistaxis	14.7% 10/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	8.3% 1/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Gastrointestinal disorders Facial pain	0.00% 0/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	8.3% 1/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Injury, poisoning and procedural complications Fall	7.4% 5/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	16.7% 2/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Gastrointestinal disorders Fatigue	94.1% 64/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	75.0% 9/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Blood and lymphatic system disorders Febrile neutropenia	2.9% 2/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	8.3% 1/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Gastrointestinal disorders Fever	25.0% 17/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	25.0% 3/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Musculoskeletal and connective tissue disorders Flank pain	5.9% 4/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	8.3% 1/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
General disorders Flu like symptoms	1.5% 1/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	8.3% 1/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Injury, poisoning and procedural complications Fracture	1.5% 1/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	8.3% 1/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Gastrointestinal disorders Gastroesophagial reflux disease	19.1% 13/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	8.3% 1/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.
Gastrointestinal disorders Gastrointestinal disorders - Other	5.9% 4/68 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.	25.0% 3/12 • 60 months Molecular arms/groups are combined for this analysis because the intent of the study was to compare the overall strategy of molecular-based treatment vs. not undertaking molecular-based therapy. Thus the number of patients with adverse events over the potential three lines of therapy is reported.