Trial Outcomes & Findings for Best Approach in Recurrent-Ovarian-Cancer-with Cediranib-Olaparib (NCT NCT03314740)

Results Overview

PFS is defined as time from randomization to the date of first progression or death for any cause, whichever comes first. Progression was established as the radiological disease progression according to RECIST 1.1 (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") or to clinical assessment in case radiological evaluation is not feasible due to clinical condition.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

123 participants

Primary outcome timeframe

An average of 30 months for each participant

Results posted on

2025-01-10

Participant Flow

The study was approved and activated in 7 experimental sites. The enrolment was closed on 18th October 2018 with the inclusion of 123 patients.

Participant milestones

Participant milestones
Measure	Arm A Intravenous administration of weekly Paclitaxel (dosage: 80 mg/mq) for a maximum of 6 cycles. Cycle is defined as 4 weeks. Paclitaxel: Comparator active compound	Arm B Oral administration of two experimental drugs: * Cediranib 20 mg/day given 7 days per week * Olaparib 600 mg / day (i.e. 300 mg twice a day) 7 days per week until progression, unacceptable toxicity, patient or physician decision to discontinue or death. Cediranib: Experimental compound Olaparib: Experimental compound	Arm C Oral administration of two experimental drugs: * Cediranib 20 mg/day given 5 days per week * Olaparib 600 mg / day (i.e. 300 mg twice a day) 7 days per week until progression, unacceptable toxicity, patient or physician decision to discontinue or death. Cediranib: Experimental compound Olaparib: Experimental compound
Overall Study STARTED	41	41	41
Overall Study COMPLETED	41	41	41
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Best Approach in Recurrent-Ovarian-Cancer-with Cediranib-Olaparib

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A n=41 Participants Intravenous administration of weekly Paclitaxel (dosage: 80 mg/mq) for a maximum of 6 cycles. Cycle is defined as 4 weeks. Paclitaxel: Comparator active compound	Arm B n=41 Participants Oral administration of two experimental drugs: * Cediranib 20 mg/day given 7 days per week * Olaparib 600 mg / day (i.e. 300 mg twice a day) 7 days per week until progression, unacceptable toxicity, patient or physician decision to discontinue or death. Cediranib: Experimental compound Olaparib: Experimental compound	Arm C n=41 Participants Oral administration of two experimental drugs: * Cediranib 20 mg/day given 5 days per week * Olaparib 600 mg / day (i.e. 300 mg twice a day) 7 days per week until progression, unacceptable toxicity, patient or physician decision to discontinue or death. Cediranib: Experimental compound Olaparib: Experimental compound	Total n=123 Participants Total of all reporting groups
Age, Continuous	62.6 years STANDARD_DEVIATION 8.1 • n=5 Participants	61.0 years STANDARD_DEVIATION 11.4 • n=7 Participants	61.4 years STANDARD_DEVIATION 9.4 • n=5 Participants	61.7 years STANDARD_DEVIATION 9.7 • n=4 Participants
Sex: Female, Male Female	41 Participants n=5 Participants	41 Participants n=7 Participants	41 Participants n=5 Participants	123 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) White	36 Participants n=5 Participants	38 Participants n=7 Participants	40 Participants n=5 Participants	114 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	6 Participants n=4 Participants
Previous Chemotherapy lines	2.6 lines STANDARD_DEVIATION 1.2 • n=5 Participants	3.1 lines STANDARD_DEVIATION 1.5 • n=7 Participants	2.9 lines STANDARD_DEVIATION 1.2 • n=5 Participants	2.9 lines STANDARD_DEVIATION 1.3 • n=4 Participants
BRCA mutated	4 Participants n=5 Participants	7 Participants n=7 Participants	4 Participants n=5 Participants	15 Participants n=4 Participants
Last Platinum Free interval	3.0 months STANDARD_DEVIATION 2.3 • n=5 Participants	2.5 months STANDARD_DEVIATION 1.9 • n=7 Participants	2.3 months STANDARD_DEVIATION 2.4 • n=5 Participants	2.6 months STANDARD_DEVIATION 2.2 • n=4 Participants

PRIMARY outcome

Timeframe: An average of 30 months for each participant

Population: Intention to treat population

PFS is defined as time from randomization to the date of first progression or death for any cause, whichever comes first. Progression was established as the radiological disease progression according to RECIST 1.1 (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") or to clinical assessment in case radiological evaluation is not feasible due to clinical condition.

Outcome measures

Outcome measures
Measure	Arm A n=41 Participants Intravenous administration of weekly Paclitaxel (dosage: 80 mg/mq) for a maximum of 6 cycles. Cycle is defined as 4 weeks. Paclitaxel: Comparator active compound	Arm B n=41 Participants Oral administration of two experimental drugs: * Cediranib 20 mg/day given 7 days per week * Olaparib 600 mg / day (i.e. 300 mg twice a day) 7 days per week until progression, unacceptable toxicity, patient or physician decision to discontinue or death. Cediranib: Experimental compound Olaparib: Experimental compound	Arm C n=41 Participants Oral administration of two experimental drugs: * Cediranib 20 mg/day given 5 days per week * Olaparib 600 mg / day (i.e. 300 mg twice a day) 7 days per week until progression, unacceptable toxicity, patient or physician decision to discontinue or death. Cediranib: Experimental compound Olaparib: Experimental compound
Efficacy: Progression Free Survival (PFS)	3.1 months Interval 1.9 to 6.3	5.6 months Interval 3.2 to 7.4	3.8 months Interval 2.0 to 5.8

PRIMARY outcome

Timeframe: Evacuation were collected daily for the first four weeks of treatment of experimental drugs

Population: No primary safety analysis in terms of gastrointestinal events between continuous and intermittent arm was done because neither experimental arm showed any superiority in PFS over the control arm.

Number of evacuations per day used as an index of gastro-intestinal toxicity profile of experimental drugs

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Disease assessments were scheduled every 8 weeks (+/- 1 week) from randomization for all treatment duration (an average of 3.5 months).

Population: ORR population: patients in the ITT population who received at least one dose of study treatment and had at least one radiological assessment.

Percentage of patients with an objective response as determined by RECIST 1.1

Outcome measures

Outcome measures
Measure	Arm A n=24 Participants Intravenous administration of weekly Paclitaxel (dosage: 80 mg/mq) for a maximum of 6 cycles. Cycle is defined as 4 weeks. Paclitaxel: Comparator active compound	Arm B n=39 Participants Oral administration of two experimental drugs: * Cediranib 20 mg/day given 7 days per week * Olaparib 600 mg / day (i.e. 300 mg twice a day) 7 days per week until progression, unacceptable toxicity, patient or physician decision to discontinue or death. Cediranib: Experimental compound Olaparib: Experimental compound	Arm C n=36 Participants Oral administration of two experimental drugs: * Cediranib 20 mg/day given 5 days per week * Olaparib 600 mg / day (i.e. 300 mg twice a day) 7 days per week until progression, unacceptable toxicity, patient or physician decision to discontinue or death. Cediranib: Experimental compound Olaparib: Experimental compound
Efficacy: Objective Response Rate (ORR)	9 participants	6 participants	4 participants

SECONDARY outcome

Timeframe: Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment.

Population: safety population: randomized patients receiving at least one dose of study drugs

Number of patients experiencing grade 3-4 toxicity for each toxicity according to NCI-CTCAE v. 4.03

Outcome measures

Outcome measures
Measure	Arm A n=28 Participants Intravenous administration of weekly Paclitaxel (dosage: 80 mg/mq) for a maximum of 6 cycles. Cycle is defined as 4 weeks. Paclitaxel: Comparator active compound	Arm B n=41 Participants Oral administration of two experimental drugs: * Cediranib 20 mg/day given 7 days per week * Olaparib 600 mg / day (i.e. 300 mg twice a day) 7 days per week until progression, unacceptable toxicity, patient or physician decision to discontinue or death. Cediranib: Experimental compound Olaparib: Experimental compound	Arm C n=41 Participants Oral administration of two experimental drugs: * Cediranib 20 mg/day given 5 days per week * Olaparib 600 mg / day (i.e. 300 mg twice a day) 7 days per week until progression, unacceptable toxicity, patient or physician decision to discontinue or death. Cediranib: Experimental compound Olaparib: Experimental compound
Safety: Number of Patients Experiencing Grade 3-4 Toxicity for Each Toxicity Fatigue grade≥3	0 Participants	4 Participants	5 Participants
Safety: Number of Patients Experiencing Grade 3-4 Toxicity for Each Toxicity Sepsis grade 5	1 Participants	0 Participants	0 Participants
Safety: Number of Patients Experiencing Grade 3-4 Toxicity for Each Toxicity Platelet count decreased grade≥3	0 Participants	1 Participants	0 Participants
Safety: Number of Patients Experiencing Grade 3-4 Toxicity for Each Toxicity White blood cells decreased grade≥3	1 Participants	0 Participants	0 Participants
Safety: Number of Patients Experiencing Grade 3-4 Toxicity for Each Toxicity Anemia grade≥3	0 Participants	4 Participants	6 Participants
Safety: Number of Patients Experiencing Grade 3-4 Toxicity for Each Toxicity Bone marrow hypocellular grade≥3	0 Participants	1 Participants	0 Participants
Safety: Number of Patients Experiencing Grade 3-4 Toxicity for Each Toxicity Febrile neutropenia grade≥3	0 Participants	0 Participants	1 Participants
Safety: Number of Patients Experiencing Grade 3-4 Toxicity for Each Toxicity Diarrhea grade≥3	0 Participants	2 Participants	1 Participants
Safety: Number of Patients Experiencing Grade 3-4 Toxicity for Each Toxicity Mucositis oral grade≥3	0 Participants	1 Participants	0 Participants
Safety: Number of Patients Experiencing Grade 3-4 Toxicity for Each Toxicity Nausea grade≥3	0 Participants	1 Participants	3 Participants
Safety: Number of Patients Experiencing Grade 3-4 Toxicity for Each Toxicity Vomiting grade≥3	0 Participants	0 Participants	2 Participants
Safety: Number of Patients Experiencing Grade 3-4 Toxicity for Each Toxicity Neutrophil count decreased grade≥3	2 Participants	1 Participants	1 Participants
Safety: Number of Patients Experiencing Grade 3-4 Toxicity for Each Toxicity Anorexia grade≥3	0 Participants	1 Participants	0 Participants
Safety: Number of Patients Experiencing Grade 3-4 Toxicity for Each Toxicity Myelodysplastic syndrome grade 5	0 Participants	1 Participants	0 Participants
Safety: Number of Patients Experiencing Grade 3-4 Toxicity for Each Toxicity Peripheral motor neuropathy grade≥3	1 Participants	0 Participants	0 Participants
Safety: Number of Patients Experiencing Grade 3-4 Toxicity for Each Toxicity Pneumonitis grade≥3	0 Participants	1 Participants	0 Participants
Safety: Number of Patients Experiencing Grade 3-4 Toxicity for Each Toxicity Palmar-plantar erythrodysesthesia syndrome grade≥3	0 Participants	1 Participants	0 Participants
Safety: Number of Patients Experiencing Grade 3-4 Toxicity for Each Toxicity Hypertension grade≥3	0 Participants	5 Participants	6 Participants
Safety: Number of Patients Experiencing Grade 3-4 Toxicity for Each Toxicity Thromboembolic event grade≥3	0 Participants	0 Participants	1 Participants

Adverse Events

Arm A

Serious events: 3 serious events

Other events: 16 other events

Deaths: 24 deaths

Arm B

Serious events: 11 serious events

Other events: 36 other events

Deaths: 31 deaths

Arm C

Serious events: 9 serious events

Other events: 34 other events

Deaths: 34 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Arm A n=28 participants at risk Intravenous administration of weekly Paclitaxel (dosage: 80 mg/mq) for a maximum of 6 cycles. Cycle is defined as 4 weeks. Paclitaxel: Comparator active compound	Arm B n=41 participants at risk Oral administration of two experimental drugs: * Cediranib 20 mg/day given 7 days per week * Olaparib 600 mg / day (i.e. 300 mg twice a day) 7 days per week until progression, unacceptable toxicity, patient or physician decision to discontinue or death. Cediranib: Experimental compound Olaparib: Experimental compound	Arm C n=41 participants at risk Oral administration of two experimental drugs: * Cediranib 20 mg/day given 5 days per week * Olaparib 600 mg / day (i.e. 300 mg twice a day) 7 days per week until progression, unacceptable toxicity, patient or physician decision to discontinue or death. Cediranib: Experimental compound Olaparib: Experimental compound
Blood and lymphatic system disorders Anemia	32.1% 9/28 • Number of events 14 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	14.6% 6/41 • Number of events 20 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	22.0% 9/41 • Number of events 16 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed
Gastrointestinal disorders Diarrhea	7.1% 2/28 • Number of events 2 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	14.6% 6/41 • Number of events 22 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	7.3% 3/41 • Number of events 5 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed
Gastrointestinal disorders Nausea	21.4% 6/28 • Number of events 8 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	58.5% 24/41 • Number of events 39 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	53.7% 22/41 • Number of events 33 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed
Gastrointestinal disorders Vomiting	3.6% 1/28 • Number of events 1 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	43.9% 18/41 • Number of events 36 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	41.5% 17/41 • Number of events 27 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed
General disorders Fatigue	32.1% 9/28 • Number of events 16 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	51.2% 21/41 • Number of events 41 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	41.5% 17/41 • Number of events 29 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed
Investigations Neutrophil count decreased	10.7% 3/28 • Number of events 16 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	7.3% 3/41 • Number of events 5 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	4.9% 2/41 • Number of events 5 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed
Vascular disorders Hypertension	3.6% 1/28 • Number of events 1 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	31.7% 13/41 • Number of events 21 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	22.0% 9/41 • Number of events 19 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed

Additional Information

Elena Biagioli

Istituto di Ricerche Farmacologiche Mario Negri

Phone: +39 0239014650

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Arm A n=28 participants at risk Intravenous administration of weekly Paclitaxel (dosage: 80 mg/mq) for a maximum of 6 cycles. Cycle is defined as 4 weeks. Paclitaxel: Comparator active compound	Arm B n=41 participants at risk Oral administration of two experimental drugs: * Cediranib 20 mg/day given 7 days per week * Olaparib 600 mg / day (i.e. 300 mg twice a day) 7 days per week until progression, unacceptable toxicity, patient or physician decision to discontinue or death. Cediranib: Experimental compound Olaparib: Experimental compound	Arm C n=41 participants at risk Oral administration of two experimental drugs: * Cediranib 20 mg/day given 5 days per week * Olaparib 600 mg / day (i.e. 300 mg twice a day) 7 days per week until progression, unacceptable toxicity, patient or physician decision to discontinue or death. Cediranib: Experimental compound Olaparib: Experimental compound
Gastrointestinal disorders abdomina pain	0.00% 0/28 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	0.00% 0/41 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	2.4% 1/41 • Number of events 1 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.00% 0/28 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	0.00% 0/41 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	2.4% 1/41 • Number of events 1 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed
Blood and lymphatic system disorders Anaemia	0.00% 0/28 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	0.00% 0/41 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	2.4% 1/41 • Number of events 1 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed
Gastrointestinal disorders Ascites	7.1% 2/28 • Number of events 2 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	0.00% 0/41 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	0.00% 0/41 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed
General disorders Asthenia	0.00% 0/28 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	0.00% 0/41 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	2.4% 1/41 • Number of events 1 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed
Cardiac disorders Atrial fibrillation	0.00% 0/28 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	2.4% 1/41 • Number of events 1 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	0.00% 0/41 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed
Hepatobiliary disorders Biliary obstruction	0.00% 0/28 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	2.4% 1/41 • Number of events 1 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	0.00% 0/41 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed
Reproductive system and breast disorders Female genital tract fistula	0.00% 0/28 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	2.4% 1/41 • Number of events 1 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	0.00% 0/41 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed
Gastrointestinal disorders Ileus	0.00% 0/28 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	2.4% 1/41 • Number of events 1 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	2.4% 1/41 • Number of events 1 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed
Gastrointestinal disorders Intestinal obstruction	0.00% 0/28 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	7.3% 3/41 • Number of events 3 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	12.2% 5/41 • Number of events 5 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed
Gastrointestinal disorders Intestinal Perforation	0.00% 0/28 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	2.4% 1/41 • Number of events 1 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	0.00% 0/41 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplastic syndrome	0.00% 0/28 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	2.4% 1/41 • Number of events 1 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	0.00% 0/41 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/28 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	2.4% 1/41 • Number of events 1 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	2.4% 1/41 • Number of events 1 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/28 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	2.4% 1/41 • Number of events 1 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	0.00% 0/41 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed
Vascular disorders Thromboembolic event	3.6% 1/28 • Number of events 1 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	0.00% 0/41 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	2.4% 1/41 • Number of events 1 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed
Infections and infestations Sepsis	3.6% 1/28 • Number of events 1 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	0.00% 0/41 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed	0.00% 0/41 • Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment. Only patients receiving at least one dose of treatment were analysed