Trial Outcomes & Findings for BI 6727 (Volasertib) Randomised Trial in Ovarian Cancer (NCT NCT01121406)

NCT ID: NCT01121406

Last Updated: 2015-08-13

Results Overview

DCR was defined as the proportion of patients who had an overall response of complete response (CR), partial response (PR), or stable disease (SD).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 110 participants
• Primary outcome timeframe: Week 24
• Results posted on: 2015-08-13

Participant Flow

Overall 54 patients were treated in Volasertib arm and 55 patients were treated in Cytotoxic arm. The "Not completed" category in the Subject Disposition table represents " Treatment permanently discontinued" and "The reasons for non-completion" in the table represent "Reason for treatment discontinuation".

Participant milestones

Measure	Volasertib (BI 6727) Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.	Cytotoxic Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: * Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) * Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) * Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) * Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)
Overall Study STARTED	55	55
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	55	55

Reasons for withdrawal

Measure	Volasertib (BI 6727) Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.	Cytotoxic Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: * Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) * Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) * Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) * Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)
Overall Study Progressive disease RECIST	44	28
Overall Study Wors. or AE of underlying cancer disease	4	6
Overall Study Other AE	3	10
Overall Study Non-compliant with protocol	0	2
Overall Study Lost to Follow-up	0	1
Overall Study Refused continuation of study med.	1	2
Overall Study Reason other than specified above	2	6
Overall Study Not treated	1	0

Baseline Characteristics

BI 6727 (Volasertib) Randomised Trial in Ovarian Cancer

Baseline characteristics by cohort

Measure	Volasertib (BI 6727) n=54 Participants Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.	Cytotoxic n=55 Participants Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: * Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) * Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) * Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) * Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)	Total n=109 Participants Total of all reporting groups
Age, Continuous	61.3 years STANDARD_DEVIATION 9.88 • n=93 Participants	60.9 years STANDARD_DEVIATION 9.26 • n=4 Participants	61.1 years STANDARD_DEVIATION 9.53 • n=27 Participants
Sex: Female, Male Female	54 Participants n=93 Participants	55 Participants n=4 Participants	109 Participants n=27 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants

PRIMARY outcome

Timeframe: Week 24

Population: TS

DCR was defined as the proportion of patients who had an overall response of complete response (CR), partial response (PR), or stable disease (SD).

Outcome measures

Measure	Volasertib (BI 6727) n=54 Participants Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.	Cytotoxic n=55 Participants Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: * Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) * Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) * Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) * Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)	Cytotoxic to Volasertib Switch Patients of the cytotoxic arm who switched to treatment with Volasertib (BI 6727).
Disease Control Rate (DCR) at Week 24 According to Response Evaluation Criteria In Solid Tumours (RECIST) Version 1.1	30.6 percentage of participants Interval 18.0 to 43.2	43.1 percentage of participants Interval 29.5 to 56.7	—

SECONDARY outcome

Timeframe: From randomization until disease progression, death or study discontinuation; Up to 213 weeks

Population: TS

Progression-free survival of a patient was based on the investigator's assessment; it was defined as the number of days from the date of randomisation until the date of either disease progression or death from any cause, whichever occurred first.

Definition of disease progression according to RECIST version 1.1; Patients with measurable tumour lesions at baseline, Target-lesions: at least a 20% increase in the sum of diameters of target lesions, the sum of diameters must also demonstrate an absolute increase of at least 5 mm,taking as reference the smallest sum on study, or appearance of 1 or more new lesions.

Non-target lesions: unequivocal progression of existing non-target lesions or appearance of 1 or more new lesions Patients with non-measurable tumour lesions at baseline, Non-target lesions: requires unequivocal progression of existing non-target lesions or appearance of 1 or more new lesions

Outcome measures

Measure	Volasertib (BI 6727) n=54 Participants Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.	Cytotoxic n=55 Participants Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: * Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) * Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) * Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) * Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)	Cytotoxic to Volasertib Switch Patients of the cytotoxic arm who switched to treatment with Volasertib (BI 6727).
Progression Free Survival (PFS)	13.1 weeks Interval 6.6 to 30.1	20.6 weeks Interval 11.6 to 30.7	—

SECONDARY outcome

Timeframe: From randomization until death or study discontinuation; Up to 213 weeks

Population: TS

OS is defined as time from randomisation to death irrespective of the cause of the death.

Outcome measures

Measure	Volasertib (BI 6727) n=54 Participants Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.	Cytotoxic n=55 Participants Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: * Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) * Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) * Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) * Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)	Cytotoxic to Volasertib Switch Patients of the cytotoxic arm who switched to treatment with Volasertib (BI 6727).
Overall Survival (OS)	60.1 weeks Interval 31.3 to 95.4	68.6 weeks Interval 28.7 to 119.4	—

SECONDARY outcome

Timeframe: time from the date of randomisation until study completion/discontinuation; Up to 213 weeks

Population: TS

Best overall response (BOR) is defined as the best response recorded at any time from the date of randomisation until the end of treatment.

Missing categories signify that no tumour imaging has been performed post baseline, and therefore the response status could not be assessed.

Outcome measures

Measure	Volasertib (BI 6727) n=54 Participants Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.	Cytotoxic n=55 Participants Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: * Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) * Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) * Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) * Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)	Cytotoxic to Volasertib Switch Patients of the cytotoxic arm who switched to treatment with Volasertib (BI 6727).
Best Overall Response CR- Measurable disease	0 participants	0 participants	—
Best Overall Response PR- Measurable disease	7 participants	8 participants	—
Best Overall Response SD- Measurable disease	24 participants	24 participants	—
Best Overall Response PD- Measurable disease	14 participants	10 participants	—
Best Overall Response Missing- Measurable disease	0 participants	2 participants	—
Best Overall Response CR- Non-measurable disease	0 participants	1 participants	—
Best Overall Response Non-CR/Non-PD- Non-measurable disease	6 participants	9 participants	—
Best Overall Response PD- Non-measurable disease	3 participants	0 participants	—
Best Overall Response Missing- Non-measurable disease	0 participants	1 participants	—

SECONDARY outcome

Timeframe: At screening and every 6 weeks thereafter (Up to 213 weeks)

Population: TS

Patients were to have a pre-treatment CA-125 of at least twice the upper limit of normal to be considered for CA-125 response. Patients were not evaluable by CA-125 if they had received mouse antibodies or if they had undergone medical and/or surgical interference with their peritoneum or pleura during the previous 28 days. In eligible patients, a CA-125 response was defined as the moment the CA- 25 was reduced by 50%, with this being confirmed with a consecutive CA-125 assessment not earlier than 28 days after the previous one.

Biological response rate based on serum CA-125 levels was assessed according to the guidelines by the Gynaecologic Cancer Intergroup. Monitoring of blood levels of the tumour marker CA-125 was performed at screening and every 6 weeks thereafter.

Outcome measures

Measure	Volasertib (BI 6727) n=54 Participants Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.	Cytotoxic n=55 Participants Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: * Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) * Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) * Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) * Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)	Cytotoxic to Volasertib Switch Patients of the cytotoxic arm who switched to treatment with Volasertib (BI 6727).
Biological Tumour Response Based on Serum Cancer Antigen 125 (CA-125) According to the Gynaecologic Cancer Intergroup (GCIG) Criteria Yes	10 participants	12 participants	—
Biological Tumour Response Based on Serum Cancer Antigen 125 (CA-125) According to the Gynaecologic Cancer Intergroup (GCIG) Criteria No	33 participants	23 participants	—
Biological Tumour Response Based on Serum Cancer Antigen 125 (CA-125) According to the Gynaecologic Cancer Intergroup (GCIG) Criteria Not evaluable	4 participants	11 participants	—
Biological Tumour Response Based on Serum Cancer Antigen 125 (CA-125) According to the Gynaecologic Cancer Intergroup (GCIG) Criteria Missing	7 participants	9 participants	—

SECONDARY outcome

Timeframe: At screening and every 6 weeks thereafter (Up to 213 weeks )

Population: TS

Biological PFS including assessment of CA-125 levels was defined as the time from randomisation until the first occurrence of progressive disease according to CA-125, progressive disease according to radiological evidence, or death.

Also according to the below criterias,

• In patients with radiological measurable disease, disease progression during study treatment could not be declared on the basis of CA-125 alone.
• Patients with elevated CA-125 pre-treatment and normalization of CA-125 had to show evidence of CA-125 ≥ to two times the upper normal limit on two occasions at least one week apart or
• Patients with elevated CA-125 pre-treatment, which never normalized, had to show evidence of CA-125 ≥ to two times the nadir value on two occasions at least one week apart or
• Patients with CA-125 in the normal range pre-treatment had to show evidence of CA-125 ≥ to two times the upper normal limit on two occasions at least one week apart.

Outcome measures

Measure	Volasertib (BI 6727) n=54 Participants Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.	Cytotoxic n=55 Participants Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: * Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) * Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) * Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) * Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)	Cytotoxic to Volasertib Switch Patients of the cytotoxic arm who switched to treatment with Volasertib (BI 6727).
Biological Progression-free Survival Based on Serum Cancer Antigen 125 (CA-125) According to the Gynaecologic Cancer Intergroup (GCIG) Criteria	13.1 weeks Interval 6.6 to 25.6	20.6 weeks Interval 11.6 to 30.0	—

SECONDARY outcome

Timeframe: Every 6 weeks (Up to 213 weeks )

Population: TS

Time to deterioration in global health status/Quality of life (QOL) and symptom control assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, QLQ-OV28, and individual symptom questionnaires.

The time to deterioration was defined as the time from randomisation to a score increased (i.e. worsened) by at least 10 points from baseline (0-100 point scale). If score is missing, and patient died within 28 days after scheduled time for completion, the patient was considered deteriorated. In this case, time to deterioration is time to death.

Outcome measures

Measure	Volasertib (BI 6727) n=54 Participants Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.	Cytotoxic n=55 Participants Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: * Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) * Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) * Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) * Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)	Cytotoxic to Volasertib Switch Patients of the cytotoxic arm who switched to treatment with Volasertib (BI 6727).
Time to Deterioration in Global Health Status/Quality of Life (QOL)	NA weeks Interval 12.3 to Missing median or percentiles signify that a sufficient number of events have not yet occurred to produce these estimates.	39.6 weeks Interval 13.1 to 47.2	—

SECONDARY outcome

Timeframe: Every 6 weeks (Up to 213 weeks )

Population: TS

Time to deterioration in fatigue/Quality of life (QOL) and symptom control assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, QLQ-OV28, and individual symptom questionnaires.

The time to deterioration was defined as the time from randomisation to a score increased (i.e. worsened) by at least 10 points from baseline (0-100 point scale). If score is missing, and patient died within 28 days after scheduled time for completion, the patient was considered deteriorated. In this case, time to deterioration is time to death.

Outcome measures

Measure	Volasertib (BI 6727) n=54 Participants Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.	Cytotoxic n=55 Participants Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: * Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) * Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) * Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) * Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)	Cytotoxic to Volasertib Switch Patients of the cytotoxic arm who switched to treatment with Volasertib (BI 6727).
Time to Deterioration in Fatigue/Quality of Life (QOL)	NA weeks Interval 18.3 to Missing median or percentiles signify that a sufficient number of events have not yet occurred to produce these estimates.	67.1 weeks Interval 12.4 to Missing median or percentiles signify that a sufficient number of events have not yet occurred to produce these estimates.	—

SECONDARY outcome

Timeframe: Every 6 weeks (Up to 213 weeks )

Population: TS

Time to deterioration in pain/ Quality of life (QOL) and symptom control assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, QLQ-OV28, and individual symptom questionnaires.

The time to deterioration was defined as the time from randomisation to a score increased (i.e. worsened) by at least 10 points from baseline (0-100 point scale). If score is missing, and patient died within 28 days after scheduled time for completion, the patient was considered deteriorated. In this case, time to deterioration is time to death.

Outcome measures

Measure	Volasertib (BI 6727) n=54 Participants Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.	Cytotoxic n=55 Participants Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: * Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) * Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) * Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) * Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)	Cytotoxic to Volasertib Switch Patients of the cytotoxic arm who switched to treatment with Volasertib (BI 6727).
Time to Deterioration in Pain/ Quality of Life (QOL)	NA weeks Interval 16.6 to Missing median or percentiles signify that a sufficient number of events have not yet occurred to produce these estimates.	54.1 weeks Interval 25.0 to Missing median or percentiles signify that a sufficient number of events have not yet occurred to produce these estimates.	—

SECONDARY outcome

Timeframe: Every 6 weeks (Up to 213 weeks )

Population: TS

Time to deterioration in abdominal bloating/ Quality of life (QOL) and symptom control assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, QLQ-OV28, and individual symptom questionnaires.

The time to deterioration was defined as the time from randomisation to a score increased (i.e. worsened) by at least 10 points from baseline (0-100 point scale). If score is missing, and patient died within 28 days after scheduled time for completion, the patient was considered deteriorated. In this case, time to deterioration is time to death.

Outcome measures

Measure	Volasertib (BI 6727) n=54 Participants Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.	Cytotoxic n=55 Participants Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: * Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) * Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) * Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) * Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)	Cytotoxic to Volasertib Switch Patients of the cytotoxic arm who switched to treatment with Volasertib (BI 6727).
Time to Deterioration in Abdominal Bloating/ Quality of Life (QOL)	NA weeks Interval 12.9 to Missing median or percentiles signify that a sufficient number of events have not yet occurred to produce these estimates.	47.2 weeks Interval 17.3 to 67.1	—

SECONDARY outcome

Timeframe: Every 6 weeks (Up to 213 weeks)

Population: TS

Three most troublesome disease specific symptoms, defined by the patient at baseline.

Patients that have defined more than 3 most troublesome symptoms have not been taken into account in the analysis.

Quality of life (QOL) and symptom control assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, QLQ-OV28, and individual symptom questionnaires.

The time to deterioration was defined as the time from randomisation to a score increased (i.e. worsened) by at least 10 points from baseline (0-100 point scale). If score is missing, and patient died within 28 days after scheduled time for completion, the patient was considered deteriorated. In this case, time to deterioration is time to death.

Outcome measures

Measure	Volasertib (BI 6727) n=54 Participants Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.	Cytotoxic n=55 Participants Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: * Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) * Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) * Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) * Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)	Cytotoxic to Volasertib Switch Patients of the cytotoxic arm who switched to treatment with Volasertib (BI 6727).
Time to Deterioration in the Three Most Troublesome Disease Specific Symptoms/ Quality of Life (QOL)	NA weeks Missing median or percentiles signify that a sufficient number of events have not yet occurred to produce these estimates.	18.9 weeks Interval 6.3 to Missing median or percentiles signify that a sufficient number of events have not yet occurred to produce these estimates.	—

SECONDARY outcome

Timeframe: From first treatment administration to 21 days after the last drug administration (Up to 1403 days)

Population: TS

Incidence and intensity of adverse events according to the United States National Cancer Institute (US NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0

Outcome measures

Measure	Volasertib (BI 6727) n=54 Participants Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.	Cytotoxic n=55 Participants Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: * Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) * Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) * Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) * Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)	Cytotoxic to Volasertib Switch n=24 Participants Patients of the cytotoxic arm who switched to treatment with Volasertib (BI 6727).
Incidence and Intensity of Adverse Events According to the United States National Cancer Institute (US NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Grade 1	4 participants	3 participants	1 participants
Incidence and Intensity of Adverse Events According to the United States National Cancer Institute (US NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Grade 2	6 participants	19 participants	3 participants
Incidence and Intensity of Adverse Events According to the United States National Cancer Institute (US NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Grade 3	16 participants	25 participants	9 participants
Incidence and Intensity of Adverse Events According to the United States National Cancer Institute (US NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Grade 4	25 participants	5 participants	6 participants
Incidence and Intensity of Adverse Events According to the United States National Cancer Institute (US NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Grade 5	3 participants	3 participants	3 participants

SECONDARY outcome

Timeframe: From first treatment administration to 21 days after the last drug administration (Up to 1403 days)

Population: TS

Clinically relevant changes in laboratory and ECG data

Outcome measures

Measure	Volasertib (BI 6727) n=54 Participants Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.	Cytotoxic n=55 Participants Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: * Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) * Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) * Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) * Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)	Cytotoxic to Volasertib Switch n=24 Participants Patients of the cytotoxic arm who switched to treatment with Volasertib (BI 6727).
Clinically Relevant Changes in Laboratory and ECG Data Hepatic enzyme increased	1.9 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Clinically Relevant Changes in Laboratory and ECG Data Aspartate aminotransferase abnormal	0.0 percentage of participants	1.8 percentage of participants	0.0 percentage of participants
Clinically Relevant Changes in Laboratory and ECG Data Transaminases increased	0.0 percentage of participants	1.8 percentage of participants	0.0 percentage of participants
Clinically Relevant Changes in Laboratory and ECG Data Blood alkaline phosphatase increased	3.7 percentage of participants	12.7 percentage of participants	8.3 percentage of participants
Clinically Relevant Changes in Laboratory and ECG Data Blood creatinine increased	9.3 percentage of participants	3.6 percentage of participants	0.0 percentage of participants
Clinically Relevant Changes in Laboratory and ECG Data Platelet count decreased	9.3 percentage of participants	0.0 percentage of participants	8.3 percentage of participants
Clinically Relevant Changes in Laboratory and ECG Data Alanine aminotransferase increased	1.9 percentage of participants	9.1 percentage of participants	4.2 percentage of participants
Clinically Relevant Changes in Laboratory and ECG Data Aspartate aminotransferase increased	3.7 percentage of participants	5.5 percentage of participants	4.2 percentage of participants
Clinically Relevant Changes in Laboratory and ECG Data Blood uric acid increased	1.9 percentage of participants	5.5 percentage of participants	0.0 percentage of participants
Clinically Relevant Changes in Laboratory and ECG Data Gamma-glutamyltransferase increased	3.7 percentage of participants	5.5 percentage of participants	4.2 percentage of participants
Clinically Relevant Changes in Laboratory and ECG Data Alanine aminotransferase abnormal	0.0 percentage of participants	0.0 percentage of participants	4.2 percentage of participants
Clinically Relevant Changes in Laboratory and ECG Data Electrocardiogram QT prolonged	0.0 percentage of participants	0.0 percentage of participants	4.2 percentage of participants
Clinically Relevant Changes in Laboratory and ECG Data Haemoglobin decreased	3.7 percentage of participants	3.6 percentage of participants	4.2 percentage of participants
Clinically Relevant Changes in Laboratory and ECG Data Neutrophil count decreased	1.9 percentage of participants	0.0 percentage of participants	4.2 percentage of participants
Clinically Relevant Changes in Laboratory and ECG Data Troponin I increased	0.0 percentage of participants	0.0 percentage of participants	4.2 percentage of participants
Clinically Relevant Changes in Laboratory and ECG Data Blood lactate dehydrogenase increased	3.7 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Clinically Relevant Changes in Laboratory and ECG Data Blood magnesium decreased	3.7 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Clinically Relevant Changes in Laboratory and ECG Data White blood cell count decreased	3.7 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Clinically Relevant Changes in Laboratory and ECG Data Blood urea increased	1.9 percentage of participants	3.6 percentage of participants	0.0 percentage of participants
Clinically Relevant Changes in Laboratory and ECG Data Alanine aminotransferase decreased	1.9 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Clinically Relevant Changes in Laboratory and ECG Data Blood bilirubin increased	1.9 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Clinically Relevant Changes in Laboratory and ECG Data Blood creatine phosphokinase decreased	1.9 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Clinically Relevant Changes in Laboratory and ECG Data Blood potassium decreased	1.9 percentage of participants	0.0 percentage of participants	0.0 percentage of participants

SECONDARY outcome

Timeframe: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration

Population: All evaluable patients were to be included in the pharmacokinetic analysis. A patient was considered not evaluable if they had an important protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.

AUC (0-24); area under the concentration-time curve in plasma over the time interval from 0 to 24 hours for BI 6727 BS

Outcome measures

Measure	Volasertib (BI 6727) n=51 Participants Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.	Cytotoxic Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: * Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) * Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) * Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) * Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)	Cytotoxic to Volasertib Switch Patients of the cytotoxic arm who switched to treatment with Volasertib (BI 6727).
AUC (0-24); Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 to 24 Hours for BI 6727 BS	2140 ng*h/mL Geometric Coefficient of Variation 25.5	—	—

SECONDARY outcome

Timeframe: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration

Population: All evaluable patients were to be included in the pharmacokinetic analysis. A patient was considered not evaluable if they had an important protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.

AUC (0-24); area under the concentration-time curve in plasma over the time interval from 0 to 24 hours for CD 10899 BS (metabolite of Volasertib BI 6727)

Outcome measures

Measure	Volasertib (BI 6727) n=51 Participants Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.	Cytotoxic Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: * Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) * Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) * Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) * Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)	Cytotoxic to Volasertib Switch Patients of the cytotoxic arm who switched to treatment with Volasertib (BI 6727).
AUC (0-24); Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 to 24 Hours for CD 10899 BS	204 ng*h/mL Geometric Coefficient of Variation 65.3	—	—

SECONDARY outcome

Timeframe: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration

Population: All evaluable patients were to be included in the pharmacokinetic analysis. A patient was considered not evaluable if they had an important protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.

AUC (0-inf); area under the concentration-time curve in plasma over the time interval from 0 extrapolated to infinity for BI 6727 BS

Outcome measures

Measure	Volasertib (BI 6727) n=49 Participants Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.	Cytotoxic Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: * Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) * Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) * Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) * Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)	Cytotoxic to Volasertib Switch Patients of the cytotoxic arm who switched to treatment with Volasertib (BI 6727).
AUC (0-inf); Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 Extrapolated to Infinity for BI 6727 BS	6240 ng*h/mL Geometric Coefficient of Variation 29.8	—	—

SECONDARY outcome

Timeframe: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration

Population: All evaluable patients were to be included in the pharmacokinetic analysis. A patient was considered not evaluable if they had an important protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.

AUC (0-inf); area under the concentration-time curve in plasma over the time interval from 0 extrapolated to infinity for CD 10899 BS (metabolite of Volasertib BI 6727)

Outcome measures

Measure	Volasertib (BI 6727) n=51 Participants Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.	Cytotoxic Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: * Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) * Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) * Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) * Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)	Cytotoxic to Volasertib Switch Patients of the cytotoxic arm who switched to treatment with Volasertib (BI 6727).
AUC (0-inf); Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 Extrapolated to Infinity for CD 10899 BS	1400 ng*h/mL Geometric Coefficient of Variation 35.8	—	—

SECONDARY outcome

Timeframe: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration

Population: All evaluable patients were to be included in the pharmacokinetic analysis. A patient was considered not evaluable if they had an important protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.

Cmax; maximum measured concentration of BI 6727 BS in plasma

Outcome measures

Measure	Volasertib (BI 6727) n=51 Participants Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.	Cytotoxic Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: * Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) * Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) * Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) * Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)	Cytotoxic to Volasertib Switch Patients of the cytotoxic arm who switched to treatment with Volasertib (BI 6727).
Cmax; Maximum Measured Concentration of BI 6727 BS in Plasma	341 ng/mL Geometric Coefficient of Variation 42.2	—	—

SECONDARY outcome

Timeframe: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration

Population: All evaluable patients were to be included in the pharmacokinetic analysis. A patient was considered not evaluable if they had an important protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.

Cmax; maximum measured concentration of CD 10899 BS (metabolite of Volasertib BI 6727) in plasma

Outcome measures

Measure	Volasertib (BI 6727) n=51 Participants Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.	Cytotoxic Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: * Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) * Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) * Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) * Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)	Cytotoxic to Volasertib Switch Patients of the cytotoxic arm who switched to treatment with Volasertib (BI 6727).
Cmax; Maximum Measured Concentration of CD 10899 BS in Plasma	10.8 ng/mL Geometric Coefficient of Variation 63.4	—	—

SECONDARY outcome

Timeframe: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration

Population: All evaluable patients were to be included in the pharmacokinetic analysis. A patient was considered not evaluable if they had an important protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.

tmax; time from dosing to maximum measured concentration of BI 6727 BS in plasma

Outcome measures

Measure	Volasertib (BI 6727) n=51 Participants Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.	Cytotoxic Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: * Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) * Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) * Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) * Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)	Cytotoxic to Volasertib Switch Patients of the cytotoxic arm who switched to treatment with Volasertib (BI 6727).
Tmax; Time From Dosing to Maximum Measured Concentration of BI 6727 BS in Plasma	2.00 hours Interval 1.83 to 3.0	—	—

SECONDARY outcome

Timeframe: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration

Population: All evaluable patients were to be included in the pharmacokinetic analysis. A patient was considered not evaluable if they had an important protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.

tmax; time from dosing to maximum measured concentration of CD 10899 BS (metabolite of Volasertib BI 6727) in plasma

Outcome measures

Measure	Volasertib (BI 6727) n=51 Participants Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.	Cytotoxic Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: * Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) * Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) * Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) * Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)	Cytotoxic to Volasertib Switch Patients of the cytotoxic arm who switched to treatment with Volasertib (BI 6727).
Tmax; Time From Dosing to Maximum Measured Concentration of CD 10899 BS in Plasma	6.07 hours Interval 3.83 to 24.3	—	—

SECONDARY outcome

Timeframe: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration

Population: All evaluable patients were to be included in the pharmacokinetic analysis. A patient was considered not evaluable if they had an important protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.

t1/2; Terminal half-life of BI 6727 BS in plasma

Outcome measures

Measure	Volasertib (BI 6727) n=51 Participants Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.	Cytotoxic Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: * Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) * Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) * Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) * Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)	Cytotoxic to Volasertib Switch Patients of the cytotoxic arm who switched to treatment with Volasertib (BI 6727).
t1/2; Terminal Half-life of BI 6727 BS in Plasma	143 hours Geometric Coefficient of Variation 21.3	—	—

SECONDARY outcome

Timeframe: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration

Population: All evaluable patients were to be included in the pharmacokinetic analysis. A patient was considered not evaluable if they had an important protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.

t1/2; Terminal half-life of CD 10899 BS in plasma

Outcome measures

Measure	Volasertib (BI 6727) n=53 Participants Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.	Cytotoxic Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: * Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) * Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) * Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) * Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)	Cytotoxic to Volasertib Switch Patients of the cytotoxic arm who switched to treatment with Volasertib (BI 6727).
t1/2; Terminal Half-life of CD 10899 BS in Plasma	146 hours Geometric Coefficient of Variation 21.5	—	—

SECONDARY outcome

Timeframe: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration

Population: All evaluable patients were to be included in the pharmacokinetic analysis. A patient was considered not evaluable if they had an important protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.

MRT; Mean residence time of BI 6727 BS in the body

Outcome measures

Measure	Volasertib (BI 6727) n=49 Participants Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.	Cytotoxic Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: * Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) * Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) * Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) * Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)	Cytotoxic to Volasertib Switch Patients of the cytotoxic arm who switched to treatment with Volasertib (BI 6727).
MRT; Mean Residence Time of BI 6727 BS in the Body	118 hours Geometric Coefficient of Variation 31.2	—	—

SECONDARY outcome

Timeframe: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration

Population: All evaluable patients were to be included in the pharmacokinetic analysis. A patient was considered not evaluable if they had an important protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.

CL; total clearance of BI 6727 BS in plasma after intravenous administration

Outcome measures

Measure	Volasertib (BI 6727) n=49 Participants Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.	Cytotoxic Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: * Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) * Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) * Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) * Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)	Cytotoxic to Volasertib Switch Patients of the cytotoxic arm who switched to treatment with Volasertib (BI 6727).
CL; Total Clearance of BI 6727 BS in Plasma After Intravenous Administration	801 mL/min Geometric Coefficient of Variation 29.8	—	—

SECONDARY outcome

Timeframe: -0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration

Population: All evaluable patients were to be included in the pharmacokinetic analysis. A patient was considered not evaluable if they had an important protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.

Vss;apparent volume of distribution at steady state following intravenous administration for BI 6727 BS

Outcome measures

Measure	Volasertib (BI 6727) n=49 Participants Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.	Cytotoxic Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: * Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) * Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) * Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) * Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)	Cytotoxic to Volasertib Switch Patients of the cytotoxic arm who switched to treatment with Volasertib (BI 6727).
Vss;Apparent Volume of Distribution at Steady State Following Intravenous Administration for BI 6727 BS	5690 Litres Geometric Coefficient of Variation 25.8	—	—

SECONDARY outcome

Timeframe: 6 months

This endpoint has not been statistically analysed in the study report

Outcome measures

Outcome data not reported

Adverse Events

Volasertib (BI 6727)

Serious events: 24 serious events

Other events: 53 other events

Deaths: 0 deaths

Cytotoxic

Serious events: 19 serious events

Other events: 53 other events

Deaths: 0 deaths

Cytotoxic to Volasertib Switch

Serious events: 12 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Measure	Volasertib (BI 6727) n=54 participants at risk Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.	Cytotoxic n=55 participants at risk Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: * Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) * Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) * Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) * Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)	Cytotoxic to Volasertib Switch n=24 participants at risk Patients of the cytotoxic arm who switched to treatment with Volasertib (BI 6727).
Blood and lymphatic system disorders Anaemia	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Blood and lymphatic system disorders Febrile neutropenia	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Blood and lymphatic system disorders Neutropenia	0.00% 0/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	8.3% 2/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Blood and lymphatic system disorders Thrombocytopenia	3.7% 2/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Cardiac disorders Atrial fibrillation	0.00% 0/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	4.2% 1/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Gastrointestinal disorders Abdominal distension	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Gastrointestinal disorders Abdominal pain	7.4% 4/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	1.8% 1/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	8.3% 2/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Gastrointestinal disorders Abdominal pain upper	3.7% 2/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Gastrointestinal disorders Ascites	0.00% 0/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	1.8% 1/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Gastrointestinal disorders Constipation	0.00% 0/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	1.8% 1/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Gastrointestinal disorders Diarrhoea	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	1.8% 1/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	4.2% 1/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Gastrointestinal disorders Gastrointestinal obstruction	0.00% 0/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	1.8% 1/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Gastrointestinal disorders Ileal perforation	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Gastrointestinal disorders Ileus	3.7% 2/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Gastrointestinal disorders Intestinal obstruction	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	5.5% 3/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	4.2% 1/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Gastrointestinal disorders Large intestine perforation	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Gastrointestinal disorders Nausea	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	3.6% 2/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Gastrointestinal disorders Rectal haemorrhage	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	1.8% 1/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Gastrointestinal disorders Subileus	0.00% 0/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	1.8% 1/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Gastrointestinal disorders Vomiting	5.6% 3/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	3.6% 2/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
General disorders Chest pain	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
General disorders Condition aggravated	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
General disorders Death	0.00% 0/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	1.8% 1/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
General disorders Euthanasia	0.00% 0/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	4.2% 1/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
General disorders General physical health deterioration	0.00% 0/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	1.8% 1/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
General disorders Multi-organ failure	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
General disorders Obstruction	3.7% 2/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	1.8% 1/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
General disorders Pyrexia	3.7% 2/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	3.6% 2/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Hepatobiliary disorders Cholecystitis	0.00% 0/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	1.8% 1/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Immune system disorders Drug hypersensitivity	0.00% 0/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	1.8% 1/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Infections and infestations Device related sepsis	0.00% 0/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	4.2% 1/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Infections and infestations Pneumonia	0.00% 0/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	1.8% 1/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Infections and infestations Pyelonephritis	0.00% 0/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	1.8% 1/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Infections and infestations Sepsis	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	1.8% 1/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	4.2% 1/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Infections and infestations Urinary tract infection	0.00% 0/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	4.2% 1/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Investigations Blood alkaline phosphatase increased	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Investigations Blood creatinine increased	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Investigations Gamma-glutamyltransferase increased	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Investigations Neutrophil count decreased	0.00% 0/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	4.2% 1/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Metabolism and nutrition disorders Decreased appetite	0.00% 0/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	1.8% 1/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Metabolism and nutrition disorders Dehydration	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	4.2% 1/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma	0.00% 0/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	4.2% 1/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to heart	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm progression	0.00% 0/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	1.8% 1/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	4.2% 1/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour invasion	0.00% 0/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	4.2% 1/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Nervous system disorders Cerebrovascular accident	0.00% 0/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	1.8% 1/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Psychiatric disorders Anxiety	0.00% 0/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	1.8% 1/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Psychiatric disorders Panic reaction	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Renal and urinary disorders Pyelocaliectasis	0.00% 0/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	4.2% 1/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Respiratory, thoracic and mediastinal disorders Atelectasis	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Respiratory, thoracic and mediastinal disorders Dyspnoea	7.4% 4/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	1.8% 1/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	4.2% 1/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	3.7% 2/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Respiratory, thoracic and mediastinal disorders Respiratory distress	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Vascular disorders Hypertension	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Vascular disorders Poor venous access	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)

Other adverse events

Measure	Volasertib (BI 6727) n=54 participants at risk Volasertib (BI 6727 300 mg) was administered as intravenous infusion over 2 hours at Day 1 of each 21-day treatment course. Treatment was to be administered until disease progression or occurrence of toxicity leading to treatment discontinuation. Patients withdrawn from volasertib treatment could receive a treatment according to investigator's choice. The patients were to be followed for survival status.	Cytotoxic n=55 participants at risk Patients received a non-platinum cytotoxic single agent. The investigator chose the most appropriate drug according to patient status (previous chemotherapy effects, cumulative toxic effects, performance status, and nutritional status), the product Summary of Product Characteristics (SPC), and the local standard of care. The following non-platinum regimens were recommended because they are regarded efficacious and safe in patients with resistant ovarian cancer: * Pegylated liposomal doxorubicin (PLD): 40 mg/m² at Day 1 (1 course = 28 days) * Topotecan: 1.25 mg/m² from Days 1 to 5 (1 course = 21 days), or 4 mg/m² at Days 1, 8, and 15 (1 course = 28 days) * Paclitaxel: 80 mg/m² at Days 1, 8, 15, and 21 (1 course = 28 days) * Gemcitabine: 1000 mg/m² at Days 1 and 8 (1 course = 21 days)	Cytotoxic to Volasertib Switch n=24 participants at risk Patients of the cytotoxic arm who switched to treatment with Volasertib (BI 6727).
Blood and lymphatic system disorders Anaemia	53.7% 29/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	36.4% 20/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	20.8% 5/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Blood and lymphatic system disorders Leukopenia	27.8% 15/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	14.5% 8/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	8.3% 2/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Blood and lymphatic system disorders Lymphopenia	13.0% 7/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	14.5% 8/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Blood and lymphatic system disorders Neutropenia	63.0% 34/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	30.9% 17/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	29.2% 7/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Blood and lymphatic system disorders Thrombocytopenia	48.1% 26/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	7.3% 4/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	16.7% 4/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Gastrointestinal disorders Abdominal distension	5.6% 3/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	3.6% 2/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Gastrointestinal disorders Abdominal pain	24.1% 13/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	36.4% 20/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	20.8% 5/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Gastrointestinal disorders Abdominal pain upper	11.1% 6/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	12.7% 7/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	12.5% 3/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Gastrointestinal disorders Ascites	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	5.5% 3/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	8.3% 2/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Gastrointestinal disorders Constipation	29.6% 16/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	23.6% 13/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	20.8% 5/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Gastrointestinal disorders Diarrhoea	27.8% 15/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	21.8% 12/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	8.3% 2/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Gastrointestinal disorders Dyspepsia	11.1% 6/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	3.6% 2/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Gastrointestinal disorders Intestinal obstruction	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	5.5% 3/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Gastrointestinal disorders Nausea	35.2% 19/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	45.5% 25/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	20.8% 5/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Gastrointestinal disorders Rectal haemorrhage	5.6% 3/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	1.8% 1/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	4.2% 1/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Gastrointestinal disorders Stomatitis	5.6% 3/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	5.5% 3/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Gastrointestinal disorders Vomiting	27.8% 15/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	32.7% 18/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	8.3% 2/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
General disorders Asthenia	33.3% 18/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	47.3% 26/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	16.7% 4/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
General disorders Chest pain	7.4% 4/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	3.6% 2/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	4.2% 1/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
General disorders Fatigue	7.4% 4/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	21.8% 12/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	16.7% 4/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
General disorders Mucosal inflammation	7.4% 4/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	12.7% 7/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	4.2% 1/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
General disorders Oedema peripheral	14.8% 8/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	9.1% 5/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	12.5% 3/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
General disorders Pain	3.7% 2/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	7.3% 4/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	4.2% 1/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
General disorders Pyrexia	9.3% 5/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	7.3% 4/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	16.7% 4/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Immune system disorders Hypersensitivity	3.7% 2/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	8.3% 2/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Infections and infestations Nasopharyngitis	7.4% 4/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	3.6% 2/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	4.2% 1/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Infections and infestations Rhinitis	0.00% 0/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	5.5% 3/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Infections and infestations Urinary tract infection	3.7% 2/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	9.1% 5/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Investigations Alanine aminotransferase increased	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	9.1% 5/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	4.2% 1/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Investigations Aspartate aminotransferase increased	3.7% 2/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	5.5% 3/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	4.2% 1/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Investigations Blood alkaline phosphatase increased	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	12.7% 7/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	8.3% 2/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Investigations Blood creatinine increased	7.4% 4/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	3.6% 2/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Investigations Blood uric acid increased	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	5.5% 3/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Investigations Gamma-glutamyltransferase increased	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	5.5% 3/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	4.2% 1/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Investigations Platelet count decreased	9.3% 5/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	8.3% 2/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Investigations Weight decreased	7.4% 4/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	3.6% 2/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Metabolism and nutrition disorders Decreased appetite	20.4% 11/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	25.5% 14/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	4.2% 1/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Metabolism and nutrition disorders Hyperglycaemia	7.4% 4/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	9.1% 5/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Metabolism and nutrition disorders Hyperkalaemia	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	7.3% 4/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Metabolism and nutrition disorders Hyperuricaemia	5.6% 3/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	1.8% 1/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Metabolism and nutrition disorders Hypoalbuminaemia	3.7% 2/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	5.5% 3/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Metabolism and nutrition disorders Hypocalcaemia	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	7.3% 4/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Metabolism and nutrition disorders Hypokalaemia	13.0% 7/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	3.6% 2/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	4.2% 1/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Metabolism and nutrition disorders Hypomagnesaemia	5.6% 3/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	7.3% 4/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	4.2% 1/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Musculoskeletal and connective tissue disorders Arthralgia	7.4% 4/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	7.3% 4/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	8.3% 2/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Musculoskeletal and connective tissue disorders Back pain	13.0% 7/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	12.7% 7/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	8.3% 2/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Musculoskeletal and connective tissue disorders Muscle spasms	7.4% 4/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	3.6% 2/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	8.3% 2/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Musculoskeletal and connective tissue disorders Myalgia	7.4% 4/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	9.1% 5/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	4.2% 1/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Musculoskeletal and connective tissue disorders Pain in extremity	5.6% 3/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	5.5% 3/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	12.5% 3/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Nervous system disorders Dysgeusia	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	7.3% 4/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Nervous system disorders Headache	14.8% 8/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	7.3% 4/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Nervous system disorders Neuropathy peripheral	3.7% 2/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	14.5% 8/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Nervous system disorders Paraesthesia	5.6% 3/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	7.3% 4/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Nervous system disorders Peripheral sensory neuropathy	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	5.5% 3/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Psychiatric disorders Anxiety	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	7.3% 4/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	4.2% 1/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Psychiatric disorders Depression	0.00% 0/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	5.5% 3/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	4.2% 1/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Psychiatric disorders Insomnia	7.4% 4/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	7.3% 4/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	8.3% 2/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Respiratory, thoracic and mediastinal disorders Cough	14.8% 8/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	7.3% 4/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	4.2% 1/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.7% 2/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	9.1% 5/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Respiratory, thoracic and mediastinal disorders Epistaxis	7.4% 4/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	9.1% 5/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	4.2% 1/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	5.5% 3/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Skin and subcutaneous tissue disorders Alopecia	29.6% 16/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	21.8% 12/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	16.7% 4/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Skin and subcutaneous tissue disorders Erythema	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	7.3% 4/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Skin and subcutaneous tissue disorders Hair colour changes	1.9% 1/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	8.3% 2/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Skin and subcutaneous tissue disorders Nail toxicity	0.00% 0/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	7.3% 4/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	3.7% 2/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	7.3% 4/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)
Skin and subcutaneous tissue disorders Rash	3.7% 2/54 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	10.9% 6/55 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)	0.00% 0/24 • From first treatment administration to 21 days after the last drug administration (Up to 1403 days)

Additional Information

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