Trial Outcomes & Findings for A Study in the United States Using Electronic Medical Records (EMR) to Assess Effectiveness of Afatinib (Gilotrif) Following Pembrolizumab and Chemotherapy in the Treatment of Metastatic Squamous Cell Carcinoma of the Lung (NCT NCT04552535)

Last Updated: 2022-01-11

Results Overview

Time on treatment was defined as the interval from the start of second-line treatment until discontinuation of second-line treatment for any reason, e.g. toxicity, progression, death, patient choice. The end of 2L treatment was defined as the date of last treatment order for afatinib plus the days of supply on the last known treatment order up to the date of data collection (but not exceeding). The Kaplan-Meier (KM) method was used to estimate the median and 95% confidence interval for time on treatment.

Recruitment status

COMPLETED

Target enrollment

200 participants

Primary outcome timeframe

From the start of second-line treatment until discontinuation of second-line treatment, up to 12.3 months for afatinib treated and up to 7.5 months for chemotherapy treated patients

Results posted on

2022-01-11

Participant Flow

This retrospective, non-interventional, multi-site cohort study utilized existing data from the electronic medical records of patients with advanced or metastatic Squamous Cell Carcinoma (SqCC) of the lung treated with first-line pembrolizumab in combination with platinum-doublet chemotherapy, followed by second-line afatinib or chemotherapy.

All patients (pts) aged ≥18 years, initiated first-line (1L) pembrolizumab and platinum-based combination chemotherapy (CT) after 1st June 2018, and subsequently discontinued 1L therapy. All pts had started second-line treatment with either afatinib or any CT at least 3 months prior to date of data collection. Maximum follow-up for any pts was approx 15 months. Pts were excluded if they had received pembrolizumab in combination with platinum-based CT as part of an interventional clinical trial.

Participant milestones

Participant milestones
Measure	Second-line Afatinib Treatment Group Patients in the second-line afatinib treatment group initiated first-line pembrolizumab and platinum-based combination chemotherapy after 1st June 2018, and subsequently discontinued first-line therapy. All patients had started second-line treatment with afatinib at least 3 months prior to the date of data collection.	Second-line Chemotherapy Treatment Group Patients in the second-line chemotherapy treatment group initiated first-line pembrolizumab and platinum-based combination chemotherapy after 1st June 2018, and subsequently discontinued first-line therapy. All patients had started second-line treatment with any chemotherapy at least 3 months prior to the date of data collection.
Overall Study STARTED	99	101
Overall Study COMPLETED	99	101
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study in the United States Using Electronic Medical Records (EMR) to Assess Effectiveness of Afatinib (Gilotrif) Following Pembrolizumab and Chemotherapy in the Treatment of Metastatic Squamous Cell Carcinoma of the Lung

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Second-line Afatinib Treatment Group n=99 Participants Patients in the second-line afatinib treatment group initiated first-line pembrolizumab and platinum-based combination chemotherapy after 1st June 2018, and subsequently discontinued first-line therapy. All patients had started second-line treatment with afatinib at least 3 months prior to the date of data collection.	Second-line Chemotherapy Treatment Group n=101 Participants Patients in the second-line chemotherapy treatment group initiated first-line pembrolizumab and platinum-based combination chemotherapy after 1st June 2018, and subsequently discontinued first-line therapy. All patients had started second-line treatment with any chemotherapy at least 3 months prior to the date of data collection.	Total n=200 Participants Total of all reporting groups
Age, Continuous	67 Years n=39 Participants	66 Years n=41 Participants	67 Years n=35 Participants
Sex: Female, Male Female	43 Participants n=39 Participants	34 Participants n=41 Participants	77 Participants n=35 Participants
Sex: Female, Male Male	56 Participants n=39 Participants	67 Participants n=41 Participants	123 Participants n=35 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants
Race (NIH/OMB) Asian	6 Participants n=39 Participants	1 Participants n=41 Participants	7 Participants n=35 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants
Race (NIH/OMB) Black or African American	30 Participants n=39 Participants	23 Participants n=41 Participants	53 Participants n=35 Participants
Race (NIH/OMB) White	59 Participants n=39 Participants	73 Participants n=41 Participants	132 Participants n=35 Participants
Race (NIH/OMB) More than one race	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=39 Participants	4 Participants n=41 Participants	8 Participants n=35 Participants
Tumor histology Squamous cell only	64 Participants n=39 Participants	98 Participants n=41 Participants	162 Participants n=35 Participants
Tumor histology Mixed histology	35 Participants n=39 Participants	3 Participants n=41 Participants	38 Participants n=35 Participants
Epidermal growth factor receptor (EGFR) mutation status EGFR mutation positive	39 Participants n=39 Participants	5 Participants n=41 Participants	44 Participants n=35 Participants
Epidermal growth factor receptor (EGFR) mutation status EGFR mutation negative	28 Participants n=39 Participants	33 Participants n=41 Participants	61 Participants n=35 Participants
Epidermal growth factor receptor (EGFR) mutation status Not tested / unknown	32 Participants n=39 Participants	63 Participants n=41 Participants	95 Participants n=35 Participants
Smoking history Never smoked	12 Participants n=39 Participants	0 Participants n=41 Participants	12 Participants n=35 Participants
Smoking history Current smoker	16 Participants n=39 Participants	19 Participants n=41 Participants	35 Participants n=35 Participants
Smoking history Former smoker	71 Participants n=39 Participants	82 Participants n=41 Participants	153 Participants n=35 Participants
Eastern Cooperative Oncology Group Performance Status at initiation of second line (2L) treatment ECOG 0/1	45 Participants n=39 Participants	50 Participants n=41 Participants	95 Participants n=35 Participants
Eastern Cooperative Oncology Group Performance Status at initiation of second line (2L) treatment ECOG ≥ 2	54 Participants n=39 Participants	51 Participants n=41 Participants	105 Participants n=35 Participants
Tumor stage at initial diagnosis Tumor stage I to IIIA	13 Participants n=39 Participants	8 Participants n=41 Participants	21 Participants n=35 Participants
Tumor stage at initial diagnosis Tumor stage IIIB	7 Participants n=39 Participants	3 Participants n=41 Participants	10 Participants n=35 Participants
Tumor stage at initial diagnosis Tumor stage IV	79 Participants n=39 Participants	90 Participants n=41 Participants	169 Participants n=35 Participants
Sites of metastatic disease at initiation of second line treatment Liver	65 Participants n=39 Participants	69 Participants n=41 Participants	134 Participants n=35 Participants
Sites of metastatic disease at initiation of second line treatment Contralateral lung nodule	51 Participants n=39 Participants	43 Participants n=41 Participants	94 Participants n=35 Participants
Sites of metastatic disease at initiation of second line treatment Blood and bone marrow	41 Participants n=39 Participants	47 Participants n=41 Participants	88 Participants n=35 Participants
Sites of metastatic disease at initiation of second line treatment Adrenal gland	26 Participants n=39 Participants	48 Participants n=41 Participants	74 Participants n=35 Participants
Sites of metastatic disease at initiation of second line treatment Pleura (nodules, effusion)	24 Participants n=39 Participants	21 Participants n=41 Participants	45 Participants n=35 Participants
Sites of metastatic disease at initiation of second line treatment Intra-abdominal lymph nodes	19 Participants n=39 Participants	14 Participants n=41 Participants	33 Participants n=35 Participants
Sites of metastatic disease at initiation of second line treatment Brain	14 Participants n=39 Participants	10 Participants n=41 Participants	24 Participants n=35 Participants
Most common comorbidities at initiation of second line treatment Any comorbidity	98 Participants n=39 Participants	88 Participants n=41 Participants	186 Participants n=35 Participants
Most common comorbidities at initiation of second line treatment Hypertension	62 Participants n=39 Participants	56 Participants n=41 Participants	118 Participants n=35 Participants
Most common comorbidities at initiation of second line treatment Chronic pulmonary disease	35 Participants n=39 Participants	49 Participants n=41 Participants	84 Participants n=35 Participants
Most common comorbidities at initiation of second line treatment Cardiovascular disease	23 Participants n=39 Participants	33 Participants n=41 Participants	56 Participants n=35 Participants
Most common comorbidities at initiation of second line treatment Depression	27 Participants n=39 Participants	14 Participants n=41 Participants	41 Participants n=35 Participants
Most common comorbidities at initiation of second line treatment Diabetes without chronic complications	21 Participants n=39 Participants	16 Participants n=41 Participants	37 Participants n=35 Participants
Radiation therapy First line or prior	14 Participants n=39 Participants	10 Participants n=41 Participants	24 Participants n=35 Participants
Radiation therapy Second line	12 Participants n=39 Participants	9 Participants n=41 Participants	21 Participants n=35 Participants
Programmed death ligand 1 (PD-L1) expression level <1%	26 Participants n=39 Participants	30 Participants n=41 Participants	56 Participants n=35 Participants
Programmed death ligand 1 (PD-L1) expression level 1 to 49%	55 Participants n=39 Participants	54 Participants n=41 Participants	109 Participants n=35 Participants
Programmed death ligand 1 (PD-L1) expression level >50%	15 Participants n=39 Participants	6 Participants n=41 Participants	21 Participants n=35 Participants
Programmed death ligand 1 (PD-L1) expression level Not tested	3 Participants n=39 Participants	11 Participants n=41 Participants	14 Participants n=35 Participants

PRIMARY outcome

Timeframe: From the start of second-line treatment until discontinuation of second-line treatment, up to 12.3 months for afatinib treated and up to 7.5 months for chemotherapy treated patients

Population: All patients (pts) who initiated first-line (1L) pembrolizumab and platinum-based combination chemotherapy (CT) after 1st June 2018, and subsequently discontinued 1L therapy and had started second-line treatment with either afatinib or any CT at least 3 months prior to date of data collection.

Outcome measures

Outcome measures
Measure	Second-line Afatinib Treatment Group n=99 Participants Patients in the second-line afatinib treatment group initiated first-line pembrolizumab and platinum-based combination chemotherapy after 1st June 2018, and subsequently discontinued first-line therapy. All patients had started second-line treatment with afatinib at least 3 months prior to the date of data collection.	Second-line Chemotherapy Treatment Group n=101 Participants Patients in the second-line chemotherapy treatment group initiated first-line pembrolizumab and platinum-based combination chemotherapy after 1st June 2018, and subsequently discontinued first-line therapy. All patients had started second-line treatment with any chemotherapy at least 3 months prior to the date of data collection.
Time on Treatment With Afatinib or Chemotherapy During Second Line (2L) Treatment	7.3 months Interval 5.2 to 8.1	4.2 months Interval 3.9 to 4.9

PRIMARY outcome

Timeframe: From the start of second-line treatment until discontinuation of second-line treatment, up to 12.3 months for afatinib treated patients

Population: All patients (pts) who initiated first-line (1L) pembrolizumab and platinum-based combination chemotherapy (CT) after 1st June 2018, and subsequently discontinued 1L therapy and had started second-line treatment with afatinib at least 3 months prior to date of data collection. Only patients treated with afatinib and with squamous cell - or mixed histology were included in the analysis.

Outcome measures

Outcome measures
Measure	Second-line Afatinib Treatment Group n=64 Participants Patients in the second-line afatinib treatment group initiated first-line pembrolizumab and platinum-based combination chemotherapy after 1st June 2018, and subsequently discontinued first-line therapy. All patients had started second-line treatment with afatinib at least 3 months prior to the date of data collection.	Second-line Chemotherapy Treatment Group n=35 Participants Patients in the second-line chemotherapy treatment group initiated first-line pembrolizumab and platinum-based combination chemotherapy after 1st June 2018, and subsequently discontinued first-line therapy. All patients had started second-line treatment with any chemotherapy at least 3 months prior to the date of data collection.
Time on Treatment With Afatinib During Second Line (2L) Treatment Defined by Histology Status	5.8 months Interval 4.4 to 8.0	8.1 months Interval 5.5 to 9.9

PRIMARY outcome

Timeframe: From the start of second-line treatment until discontinuation of second-line treatment, up to 12.3 months for afatinib treated patients

Population: All patients (pts) who initiated first-line (1L) pembrolizumab and platinum-based combination chemotherapy (CT) after 1st June 2018, and subsequently discontinued 1L therapy and had started second-line treatment with afatinib at least 3 months prior to date of data collection. Only afatinib treated patients with an EGFR mutation positive or negative status were included in the analysis.

Outcome measures

Outcome measures
Measure	Second-line Afatinib Treatment Group n=39 Participants Patients in the second-line afatinib treatment group initiated first-line pembrolizumab and platinum-based combination chemotherapy after 1st June 2018, and subsequently discontinued first-line therapy. All patients had started second-line treatment with afatinib at least 3 months prior to the date of data collection.	Second-line Chemotherapy Treatment Group n=28 Participants Patients in the second-line chemotherapy treatment group initiated first-line pembrolizumab and platinum-based combination chemotherapy after 1st June 2018, and subsequently discontinued first-line therapy. All patients had started second-line treatment with any chemotherapy at least 3 months prior to the date of data collection.
Time on Treatment With Afatinib During Second Line (2L) Treatment Defined by Epidermal Growth Factor Receptor (EGFR) Mutation Status	7.4 months Interval 5.6 to 8.6	5.9 months Interval 4.4 to not estimable due to unsufficient events

PRIMARY outcome

Timeframe: From the start of second-line treatment to the end of follow-up, up to 15 months

Chart abstractors (i.e. the patients treating physician) were asked to abstract information regarding severe (grade 3 or higher) irAEs of specific interest (including pneumonitis, colitis, hepatitis, interstitial lung disease, higher indeterminate pulmonary events, death, or discontinuation of therapy due to toxicity) during first line (1L) treatment and second line (2L) for both patients treated with afatinib in 2L and those treated with chemotherapy in 2L. Providers/abstractors were asked only if these specific immune related events occurred.

Outcome measures

Outcome measures
Measure	Second-line Afatinib Treatment Group n=99 Participants Patients in the second-line afatinib treatment group initiated first-line pembrolizumab and platinum-based combination chemotherapy after 1st June 2018, and subsequently discontinued first-line therapy. All patients had started second-line treatment with afatinib at least 3 months prior to the date of data collection.	Second-line Chemotherapy Treatment Group n=101 Participants Patients in the second-line chemotherapy treatment group initiated first-line pembrolizumab and platinum-based combination chemotherapy after 1st June 2018, and subsequently discontinued first-line therapy. All patients had started second-line treatment with any chemotherapy at least 3 months prior to the date of data collection.
Number of Patients With Severe Immune-related Adverse Events (irAEs) of Specific Interest During Second-line Treatment	6 Participants	0 Participants

Adverse Events

Second-line Afatinib Treatment Group

Serious events: 0 serious events

Other events: 37 other events

Deaths: 2 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Second-line Afatinib Treatment Group n=99 participants at risk Patients in the second-line afatinib treatment group initiated first-line pembrolizumab and platinum-based combination chemotherapy after 1st June 2018, and subsequently discontinued first-line therapy. All patients had started second-line treatment with afatinib at least 3 months prior to the date of data collection.
Gastrointestinal disorders Diarrhea	26.3% 26/99 • From the start of second-line treatment to the end of follow-up, up to 15 months. Adverse events (AEs) were only collected and reported for 2L afatinib treatment group according to protocol requirements. All 2L afatinib treatment group patients (pts) who initiated first-line (1L) pembrolizumab and platinum-based combination chemotherapy (CT) after 1st June 2018, and subsequently discontinued 1L therapy and had started second-line (2L) treatment with afatinib at least 3 months prior to date of data collection. Serious AEs were not collected and reported for this study.
Skin and subcutaneous tissue disorders Skin rash	6.1% 6/99 • From the start of second-line treatment to the end of follow-up, up to 15 months. Adverse events (AEs) were only collected and reported for 2L afatinib treatment group according to protocol requirements. All 2L afatinib treatment group patients (pts) who initiated first-line (1L) pembrolizumab and platinum-based combination chemotherapy (CT) after 1st June 2018, and subsequently discontinued 1L therapy and had started second-line (2L) treatment with afatinib at least 3 months prior to date of data collection. Serious AEs were not collected and reported for this study.
General disorders Fatigue	5.1% 5/99 • From the start of second-line treatment to the end of follow-up, up to 15 months. Adverse events (AEs) were only collected and reported for 2L afatinib treatment group according to protocol requirements. All 2L afatinib treatment group patients (pts) who initiated first-line (1L) pembrolizumab and platinum-based combination chemotherapy (CT) after 1st June 2018, and subsequently discontinued 1L therapy and had started second-line (2L) treatment with afatinib at least 3 months prior to date of data collection. Serious AEs were not collected and reported for this study.
Gastrointestinal disorders Nausea	5.1% 5/99 • From the start of second-line treatment to the end of follow-up, up to 15 months. Adverse events (AEs) were only collected and reported for 2L afatinib treatment group according to protocol requirements. All 2L afatinib treatment group patients (pts) who initiated first-line (1L) pembrolizumab and platinum-based combination chemotherapy (CT) after 1st June 2018, and subsequently discontinued 1L therapy and had started second-line (2L) treatment with afatinib at least 3 months prior to date of data collection. Serious AEs were not collected and reported for this study.
Gastrointestinal disorders Stomatitis	5.1% 5/99 • From the start of second-line treatment to the end of follow-up, up to 15 months. Adverse events (AEs) were only collected and reported for 2L afatinib treatment group according to protocol requirements. All 2L afatinib treatment group patients (pts) who initiated first-line (1L) pembrolizumab and platinum-based combination chemotherapy (CT) after 1st June 2018, and subsequently discontinued 1L therapy and had started second-line (2L) treatment with afatinib at least 3 months prior to date of data collection. Serious AEs were not collected and reported for this study.

Additional Information

Boehringer Ingelheim, Call Centre

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER