Trial Outcomes & Findings for Cabozantinib and Temozolomide for the Treatment of Unresectable or Metastatic Leiomyosarcoma or Other Soft Tissue Sarcoma (NCT NCT04200443)

NCT ID: NCT04200443

Last Updated: 2026-05-01

Results Overview

Progression will be evaluated in this study using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1). Per RECIST v1.1 criteria, for target lesions, progression is defined as at least a 20% increase in the sum of the longest diameter or the appearance of one or more new lesions; For non-target lesions, progression is defined as the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. PFS will be the time from the start of treatment to the time of progression, unequivocal clinical deterioration, or death from any cause. The proportion of patients who had a PFS event was calculated.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

96 participants

Primary outcome timeframe

After the first 12 weeks of therapy

Results posted on

2026-05-01

Participant Flow

Between January 2020 and February 2023, 96 patients were assessed for eligibility, 24 were ineligible, and 72 were enrolled and included in the final analysis.

Participant milestones

Participant milestones
Measure	Cohort 1 - Patients With Unresectable or Metastatic Uterine and Non-uterine Leiomyosarcoma Patients received oral cabozantinib 40 mg (as a starting dose) once per day and temozolomide 150 mg/m² on days 1-5 of a 28-day cycle for cycle one. Starting from cycle two, temozolomide was escalated to 200 mg/m² on days 1-5 of each cycle, if the absolute neutrophil count was more than 1·5 × 10⁹/L and platelet count was more than 100·0 × 10⁹/L. Treatment was continued until disease progression or unacceptable drug-related toxicity.	Cohort 2 - Patients With Other Soft Tissue Sarcomas Patients with gastrointestinal stromal tumour, dermatofibrosarcoma, alveolar soft part sarcoma, kaposi sarcoma, mixed mesodermal tumour or carcinosarcoma, alveolar and embryonal rhabdomyosarcoma, and low grade sarcomas were not included. Patients received oral cabozantinib 40 mg (as a starting dose) once per day and temozolomide 150 mg/m² on days 1-5 of a 28-day cycle for cycle one. Starting from cycle two, temozolomide was escalated to 200 mg/m² on days 1-5 of each cycle, if the absolute neutrophil count was more than 1·5 × 10⁹/L and platelet count was more than 100·0 × 10⁹/L. Treatment was continued until disease progression or unacceptable drug-related toxicity.
Overall Study STARTED	42	30
Overall Study COMPLETED	42	30
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Cabozantinib and Temozolomide for the Treatment of Unresectable or Metastatic Leiomyosarcoma or Other Soft Tissue Sarcoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 - Patients With Unresectable or Metastatic Uterine and Non-uterine Leiomyosarcoma n=42 Participants Patients received oral cabozantinib 40 mg (as a starting dose) once per day and temozolomide 150 mg/m² on days 1-5 of a 28-day cycle for cycle one. Starting from cycle two, temozolomide was escalated to 200 mg/m² on days 1-5 of each cycle, if the absolute neutrophil count was more than 1·5 × 10⁹/L and platelet count was more than 100·0 × 10⁹/L. Treatment was continued until disease progression or unacceptable drug-related toxicity.	Cohort 2 - Patients With Other Soft Tissue Sarcomas n=30 Participants Patients with gastrointestinal stromal tumour, dermatofibrosarcoma, alveolar soft part sarcoma, kaposi sarcoma, mixed mesodermal tumour or carcinosarcoma, alveolar and embryonal rhabdomyosarcoma, and low grade sarcomas were not included. Patients received oral cabozantinib 40 mg (as a starting dose) once per day and temozolomide 150 mg/m² on days 1-5 of a 28-day cycle for cycle one. Starting from cycle two, temozolomide was escalated to 200 mg/m² on days 1-5 of each cycle, if the absolute neutrophil count was more than 1·5 × 10⁹/L and platelet count was more than 100·0 × 10⁹/L. Treatment was continued until disease progression or unacceptable drug-related toxicity.	Total n=72 Participants Total of all reporting groups
Age, Continuous	59 years n=14 Participants	63 years n=34 Participants	60 years n=69 Participants
Sex: Female, Male Female	31 Participants n=14 Participants	11 Participants n=34 Participants	42 Participants n=69 Participants
Sex: Female, Male Male	11 Participants n=14 Participants	19 Participants n=34 Participants	30 Participants n=69 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=14 Participants	5 Participants n=34 Participants	9 Participants n=69 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	36 Participants n=14 Participants	25 Participants n=34 Participants	61 Participants n=69 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=14 Participants	0 Participants n=34 Participants	2 Participants n=69 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=14 Participants	0 Participants n=34 Participants	1 Participants n=69 Participants
Race (NIH/OMB) Asian	2 Participants n=14 Participants	0 Participants n=34 Participants	2 Participants n=69 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=14 Participants	0 Participants n=34 Participants	0 Participants n=69 Participants
Race (NIH/OMB) Black or African American	2 Participants n=14 Participants	2 Participants n=34 Participants	4 Participants n=69 Participants
Race (NIH/OMB) White	34 Participants n=14 Participants	26 Participants n=34 Participants	60 Participants n=69 Participants
Race (NIH/OMB) More than one race	0 Participants n=14 Participants	0 Participants n=34 Participants	0 Participants n=69 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=14 Participants	2 Participants n=34 Participants	5 Participants n=69 Participants
Region of Enrollment United States	42 participants n=14 Participants	30 participants n=34 Participants	72 participants n=69 Participants

PRIMARY outcome

Timeframe: After the first 12 weeks of therapy

Outcome measures

Outcome measures
Measure	Cohort 1 - Patients With Unresectable or Metastatic Uterine and Non-uterine Leiomyosarcoma n=42 Participants Patients received oral cabozantinib 40 mg (as a starting dose) once per day and temozolomide 150 mg/m² on days 1-5 of a 28-day cycle for cycle one. Starting from cycle two, temozolomide was escalated to 200 mg/m² on days 1-5 of each cycle, if the absolute neutrophil count was more than 1·5 × 10⁹/L and platelet count was more than 100·0 × 10⁹/L. Treatment was continued until disease progression or unacceptable drug-related toxicity.	Cohort 2 - Patients With Other Soft Tissue Sarcomas n=30 Participants Patients with gastrointestinal stromal tumour, dermatofibrosarcoma, alveolar soft part sarcoma, kaposi sarcoma, mixed mesodermal tumour or carcinosarcoma, alveolar and embryonal rhabdomyosarcoma, and low grade sarcomas were not included. Patients received oral cabozantinib 40 mg (as a starting dose) once per day and temozolomide 150 mg/m² on days 1-5 of a 28-day cycle for cycle one. Starting from cycle two, temozolomide was escalated to 200 mg/m² on days 1-5 of each cycle, if the absolute neutrophil count was more than 1·5 × 10⁹/L and platelet count was more than 100·0 × 10⁹/L. Treatment was continued until disease progression or unacceptable drug-related toxicity.
Progression-free Survival (PFS)	33 Participants	29 Participants

SECONDARY outcome

Timeframe: At weeks 6 and 12, then every 2 cycles up to 5 years

Response will be evaluated in this study using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1). Per RECIST v1.1 for target lesions: Complete Response (CR), Disappearance of all target lesions. Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; For non-target lesions, CR: Disappearance of all non-target lesions. Overall Response (OR) = CR + PR. Defined as patients who reached an objective tumour response (eg, partial or complete response) according to RECIST by cycle four.

Outcome measures

Outcome measures
Measure	Cohort 1 - Patients With Unresectable or Metastatic Uterine and Non-uterine Leiomyosarcoma n=42 Participants Patients received oral cabozantinib 40 mg (as a starting dose) once per day and temozolomide 150 mg/m² on days 1-5 of a 28-day cycle for cycle one. Starting from cycle two, temozolomide was escalated to 200 mg/m² on days 1-5 of each cycle, if the absolute neutrophil count was more than 1·5 × 10⁹/L and platelet count was more than 100·0 × 10⁹/L. Treatment was continued until disease progression or unacceptable drug-related toxicity.	Cohort 2 - Patients With Other Soft Tissue Sarcomas n=30 Participants Patients with gastrointestinal stromal tumour, dermatofibrosarcoma, alveolar soft part sarcoma, kaposi sarcoma, mixed mesodermal tumour or carcinosarcoma, alveolar and embryonal rhabdomyosarcoma, and low grade sarcomas were not included. Patients received oral cabozantinib 40 mg (as a starting dose) once per day and temozolomide 150 mg/m² on days 1-5 of a 28-day cycle for cycle one. Starting from cycle two, temozolomide was escalated to 200 mg/m² on days 1-5 of each cycle, if the absolute neutrophil count was more than 1·5 × 10⁹/L and platelet count was more than 100·0 × 10⁹/L. Treatment was continued until disease progression or unacceptable drug-related toxicity.
Presence of Response	7 Participants	2 Participants

SECONDARY outcome

Timeframe: At weeks 6 and 12, then every 2 cycles up to 5 years

Response will be evaluated in this study using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1). Per RECIST v1.1 for target lesions: Complete Response (CR), Disappearance of all target lesions. Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions. Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease; For non-target lesions, CR: Disappearance of all non-target lesions. Stable Disease (SD), Persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits. Clinical Benefit = CR + PR + SD. Defined as the number of patients with complete, partial response, or stable disease.

Outcome measures

Outcome measures
Measure	Cohort 1 - Patients With Unresectable or Metastatic Uterine and Non-uterine Leiomyosarcoma n=42 Participants Patients received oral cabozantinib 40 mg (as a starting dose) once per day and temozolomide 150 mg/m² on days 1-5 of a 28-day cycle for cycle one. Starting from cycle two, temozolomide was escalated to 200 mg/m² on days 1-5 of each cycle, if the absolute neutrophil count was more than 1·5 × 10⁹/L and platelet count was more than 100·0 × 10⁹/L. Treatment was continued until disease progression or unacceptable drug-related toxicity.	Cohort 2 - Patients With Other Soft Tissue Sarcomas n=30 Participants Patients with gastrointestinal stromal tumour, dermatofibrosarcoma, alveolar soft part sarcoma, kaposi sarcoma, mixed mesodermal tumour or carcinosarcoma, alveolar and embryonal rhabdomyosarcoma, and low grade sarcomas were not included. Patients received oral cabozantinib 40 mg (as a starting dose) once per day and temozolomide 150 mg/m² on days 1-5 of a 28-day cycle for cycle one. Starting from cycle two, temozolomide was escalated to 200 mg/m² on days 1-5 of each cycle, if the absolute neutrophil count was more than 1·5 × 10⁹/L and platelet count was more than 100·0 × 10⁹/L. Treatment was continued until disease progression or unacceptable drug-related toxicity.
Clinical Benefit Rate	27 Participants	13 Participants

SECONDARY outcome

Timeframe: Up to 5 years

Progression will be evaluated in this study using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1). Per RECIST v1.1 criteria, for target lesions, progression is defined as at least a 20% increase in the sum of the longest diameter or the appearance of one or more new lesions; For non-target lesions, progression is defined as the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Will assess the time from the first dose of study treatment until progression based upon changes in RECIST 1.1, unequivocal clinical deterioration, or death from any cause.

Outcome measures

Outcome measures
Measure	Cohort 1 - Patients With Unresectable or Metastatic Uterine and Non-uterine Leiomyosarcoma n=42 Participants Patients received oral cabozantinib 40 mg (as a starting dose) once per day and temozolomide 150 mg/m² on days 1-5 of a 28-day cycle for cycle one. Starting from cycle two, temozolomide was escalated to 200 mg/m² on days 1-5 of each cycle, if the absolute neutrophil count was more than 1·5 × 10⁹/L and platelet count was more than 100·0 × 10⁹/L. Treatment was continued until disease progression or unacceptable drug-related toxicity.	Cohort 2 - Patients With Other Soft Tissue Sarcomas n=30 Participants Patients with gastrointestinal stromal tumour, dermatofibrosarcoma, alveolar soft part sarcoma, kaposi sarcoma, mixed mesodermal tumour or carcinosarcoma, alveolar and embryonal rhabdomyosarcoma, and low grade sarcomas were not included. Patients received oral cabozantinib 40 mg (as a starting dose) once per day and temozolomide 150 mg/m² on days 1-5 of a 28-day cycle for cycle one. Starting from cycle two, temozolomide was escalated to 200 mg/m² on days 1-5 of each cycle, if the absolute neutrophil count was more than 1·5 × 10⁹/L and platelet count was more than 100·0 × 10⁹/L. Treatment was continued until disease progression or unacceptable drug-related toxicity.
Median Progression Free Survival	6.3 months Interval 4.6 to 7.0	3.0 months Interval 1.4 to 4.6

SECONDARY outcome

Timeframe: Up to 2 years

Will assess the time from the first dose of the study treatment until death from any cause, up to a maximum follow-up of two years.

Outcome measures

Outcome measures
Measure	Cohort 1 - Patients With Unresectable or Metastatic Uterine and Non-uterine Leiomyosarcoma n=42 Participants Patients received oral cabozantinib 40 mg (as a starting dose) once per day and temozolomide 150 mg/m² on days 1-5 of a 28-day cycle for cycle one. Starting from cycle two, temozolomide was escalated to 200 mg/m² on days 1-5 of each cycle, if the absolute neutrophil count was more than 1·5 × 10⁹/L and platelet count was more than 100·0 × 10⁹/L. Treatment was continued until disease progression or unacceptable drug-related toxicity.	Cohort 2 - Patients With Other Soft Tissue Sarcomas n=30 Participants Patients with gastrointestinal stromal tumour, dermatofibrosarcoma, alveolar soft part sarcoma, kaposi sarcoma, mixed mesodermal tumour or carcinosarcoma, alveolar and embryonal rhabdomyosarcoma, and low grade sarcomas were not included. Patients received oral cabozantinib 40 mg (as a starting dose) once per day and temozolomide 150 mg/m² on days 1-5 of a 28-day cycle for cycle one. Starting from cycle two, temozolomide was escalated to 200 mg/m² on days 1-5 of each cycle, if the absolute neutrophil count was more than 1·5 × 10⁹/L and platelet count was more than 100·0 × 10⁹/L. Treatment was continued until disease progression or unacceptable drug-related toxicity.
Overall Survival (OS)	19.2 months Interval 11.4 to Upper limit can not be estimated due to insufficient number of patients with events.	7.7 months Interval 4.8 to 10.9

SECONDARY outcome

Timeframe: From time of first treatment up to the end of last treatment, up to 5 years

Will assess the presence of all toxicities outlined in National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Outcome measures

Outcome measures
Measure	Cohort 1 - Patients With Unresectable or Metastatic Uterine and Non-uterine Leiomyosarcoma n=42 Participants Patients received oral cabozantinib 40 mg (as a starting dose) once per day and temozolomide 150 mg/m² on days 1-5 of a 28-day cycle for cycle one. Starting from cycle two, temozolomide was escalated to 200 mg/m² on days 1-5 of each cycle, if the absolute neutrophil count was more than 1·5 × 10⁹/L and platelet count was more than 100·0 × 10⁹/L. Treatment was continued until disease progression or unacceptable drug-related toxicity.	Cohort 2 - Patients With Other Soft Tissue Sarcomas n=30 Participants Patients with gastrointestinal stromal tumour, dermatofibrosarcoma, alveolar soft part sarcoma, kaposi sarcoma, mixed mesodermal tumour or carcinosarcoma, alveolar and embryonal rhabdomyosarcoma, and low grade sarcomas were not included. Patients received oral cabozantinib 40 mg (as a starting dose) once per day and temozolomide 150 mg/m² on days 1-5 of a 28-day cycle for cycle one. Starting from cycle two, temozolomide was escalated to 200 mg/m² on days 1-5 of each cycle, if the absolute neutrophil count was more than 1·5 × 10⁹/L and platelet count was more than 100·0 × 10⁹/L. Treatment was continued until disease progression or unacceptable drug-related toxicity.
Number of Participants With Adverse Events	41 Participants	30 Participants

SECONDARY outcome

Timeframe: Outcomes are measured at Cycle 1 to Cycle 4 between responders and non-responders

Population: This objective was analyzed differently to investigate the link between symptom burden and treatment response; therefore, results are reported by response status (responders vs non-responders).

Will be assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) symptom score. The QLQ-C30 questionnaire is made up of 30 questions and contains five functional scales (physical, role, emotional, cognitive, and social functioning), a global QoL scale, three symptom scales (fatigue, nausea and vomiting, and pain), and six single items (appetite loss, diarrhea, dyspnea, constipation, insomnia, and financial impact). The questionnaire uses a four-point response scale ("not at all", "a little", "quite a bit", and "very much"), with the exception of the global QoL scale, which has a seven-point response format. The scores were linearly transformed to a score between 0 and 100. For the functioning and the global QoL scales, a higher score indicates better health. For the symptoms scales, a higher score indicates more symptom burden. Linearly transformed scores for the nausea and vomiting item are reported here.

Outcome measures

Outcome measures
Measure	Cohort 1 - Patients With Unresectable or Metastatic Uterine and Non-uterine Leiomyosarcoma n=9 Participants Patients received oral cabozantinib 40 mg (as a starting dose) once per day and temozolomide 150 mg/m² on days 1-5 of a 28-day cycle for cycle one. Starting from cycle two, temozolomide was escalated to 200 mg/m² on days 1-5 of each cycle, if the absolute neutrophil count was more than 1·5 × 10⁹/L and platelet count was more than 100·0 × 10⁹/L. Treatment was continued until disease progression or unacceptable drug-related toxicity.	Cohort 2 - Patients With Other Soft Tissue Sarcomas n=36 Participants Patients with gastrointestinal stromal tumour, dermatofibrosarcoma, alveolar soft part sarcoma, kaposi sarcoma, mixed mesodermal tumour or carcinosarcoma, alveolar and embryonal rhabdomyosarcoma, and low grade sarcomas were not included. Patients received oral cabozantinib 40 mg (as a starting dose) once per day and temozolomide 150 mg/m² on days 1-5 of a 28-day cycle for cycle one. Starting from cycle two, temozolomide was escalated to 200 mg/m² on days 1-5 of each cycle, if the absolute neutrophil count was more than 1·5 × 10⁹/L and platelet count was more than 100·0 × 10⁹/L. Treatment was continued until disease progression or unacceptable drug-related toxicity.
Subject-reported Outcomes Cycle 1	5.8 score on a scale Interval 0.0 to 15.9	7.1 score on a scale Interval 3.5 to 10.8
Subject-reported Outcomes Cycle 2	5.6 score on a scale Interval 0.0 to 15.8	12.9 score on a scale Interval 8.8 to 17.0
Subject-reported Outcomes Cycle 3	7.4 score on a scale Interval 0.0 to 19.0	15.9 score on a scale Interval 10.5 to 21.2
Subject-reported Outcomes Cycle 4	14.8 score on a scale Interval 1.2 to 28.4	19.7 score on a scale Interval 13.3 to 26.1

Adverse Events

Cohort 1 - Patients With Unresectable or Metastatic Uterine and Non-uterine Leiomyosarcoma

Serious events: 9 serious events

Other events: 42 other events

Deaths: 25 deaths

Cohort 2 - Patients With Other Soft Tissue Sarcomas

Serious events: 11 serious events

Other events: 29 other events

Deaths: 26 deaths

Serious adverse events

Other adverse events

Additional Information

Paul Frankel, Ph.D.

City of Hope

Phone: 6262185265

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Cohort 1 - Patients With Unresectable or Metastatic Uterine and Non-uterine Leiomyosarcoma n=42 participants at risk Patients received oral cabozantinib 40 mg (as a starting dose) once per day and temozolomide 150 mg/m² on days 1-5 of a 28-day cycle for cycle one. Starting from cycle two, temozolomide was escalated to 200 mg/m² on days 1-5 of each cycle, if the absolute neutrophil count was more than 1·5 × 10⁹/L and platelet count was more than 100·0 × 10⁹/L. Treatment was continued until disease progression or unacceptable drug-related toxicity.	Cohort 2 - Patients With Other Soft Tissue Sarcomas n=30 participants at risk Patients with gastrointestinal stromal tumour, dermatofibrosarcoma, alveolar soft part sarcoma, kaposi sarcoma, mixed mesodermal tumour or carcinosarcoma, alveolar and embryonal rhabdomyosarcoma, and low grade sarcomas were not included. Patients received oral cabozantinib 40 mg (as a starting dose) once per day and temozolomide 150 mg/m² on days 1-5 of a 28-day cycle for cycle one. Starting from cycle two, temozolomide was escalated to 200 mg/m² on days 1-5 of each cycle, if the absolute neutrophil count was more than 1·5 × 10⁹/L and platelet count was more than 100·0 × 10⁹/L. Treatment was continued until disease progression or unacceptable drug-related toxicity.
Cardiac disorders Myocardial infarction	0.00% 0/42 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Cardiac disorders Pericardial effusion	2.4% 1/42 • Number of events 1 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/30 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Abdominal pain	0.00% 0/42 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Constipation	2.4% 1/42 • Number of events 1 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/30 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Diarrhea	0.00% 0/42 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Small intestinal perforation	2.4% 1/42 • Number of events 1 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/30 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Death NOS	0.00% 0/42 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Disease progression	4.8% 2/42 • Number of events 2 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Hepatobiliary disorders Cholecystitis	2.4% 1/42 • Number of events 1 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/30 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Injury, poisoning and procedural complications Fall	2.4% 1/42 • Number of events 1 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/30 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Platelet count decreased	2.4% 1/42 • Number of events 7 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/30 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/42 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	2.4% 1/42 • Number of events 1 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/30 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Headache	2.4% 1/42 • Number of events 1 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/30 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Syncope	2.4% 1/42 • Number of events 1 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders altered mental status	0.00% 0/42 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Renal and urinary disorders Cystitis noninfective	2.4% 1/42 • Number of events 1 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/30 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Renal and urinary disorders Hematuria	0.00% 0/42 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Dyspnea	4.8% 2/42 • Number of events 2 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	6.7% 2/30 • Number of events 2 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.4% 1/42 • Number of events 1 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/30 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Respiratory failure	2.4% 1/42 • Number of events 2 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Vascular disorders Hematoma	0.00% 0/42 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Vascular disorders Pulmonary embolism	0.00% 0/42 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	3.3% 1/30 • Number of events 1 • Adverse events were assessed from the time of initial treatment up to the end of last treatment, up to 5 years. All-Cause Mortality was assessed from start of treatment to time of death, up to 5 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.