Trial Outcomes & Findings for Clinical Trial of Lurbinectedin (PM01183) in Platinum Resistant Ovarian Cancer Patients (NCT NCT02421588)

NCT ID: NCT02421588

Last Updated: 2020-04-03

Results Overview

The primary endpoint was PFS by IRC assessment, defined as the time from the date of randomization to the date of documented progression per RECIST v.1.1 or death (regardless of the cause of death). If the patient received further antitumor therapy or was lost to follow-up before PD, PFS was censored at the date of last tumor assessment before the date of subsequent antitumor treatment.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 442 participants
• Primary outcome timeframe: Time from the date of randomization to the date of PD, death (of any cause), or last tumor evaluation, whichever came first, assessed up to 3 years
• Results posted on: 2020-04-03

Participant Flow

First randomization/first study treatment administration took place on 26JUN2015. The cutoff date for results was 12OCT2018. 534 patients were screened; 442 were randomized at 83 sites/12 countries. 10 patients did not receive the study treatment.

IC;Age≥18 years;confirmed diagnosis of unresectable epithelial ovarian, fallopian tube or primary peritoneal cancer;Platinum-resistant disease;ECOG PS≤2;Adequate hematological, renal, metabolic, and hepatic function

Participant milestones

Measure	Lurbinectedin 3.2 mg/m2 i.v. as a 1-hour infusion on Day 1 q3wk (three weeks = one treatment cycle) through peripheral or central lines. A minimum total volume of 100 mL, diluted in 5% glucose or 0.9% sodium chloride solution for infusion, had to be used for administration through a central venous catheter; if a peripheral venous catheter was used, the minimum volume was 250 mL	Control (PLD or Topotecan) Patients randomized to the Control arm were assigned to receive PLD if they had previously been treated with topotecan, or to receive topotecan if they had previously been treated with PLD. However, if the number of patients randomized to either PLD or topotecan reached 60% (i.e., 126 patients) of the total number of patients expected in the Control Arm, then the treatment of choice in the Control Arm would be restricted to the less frequent control drug until the end of accrual
Overall Study STARTED	221	221
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	221	221

Reasons for withdrawal

Measure	Lurbinectedin 3.2 mg/m2 i.v. as a 1-hour infusion on Day 1 q3wk (three weeks = one treatment cycle) through peripheral or central lines. A minimum total volume of 100 mL, diluted in 5% glucose or 0.9% sodium chloride solution for infusion, had to be used for administration through a central venous catheter; if a peripheral venous catheter was used, the minimum volume was 250 mL	Control (PLD or Topotecan) Patients randomized to the Control arm were assigned to receive PLD if they had previously been treated with topotecan, or to receive topotecan if they had previously been treated with PLD. However, if the number of patients randomized to either PLD or topotecan reached 60% (i.e., 126 patients) of the total number of patients expected in the Control Arm, then the treatment of choice in the Control Arm would be restricted to the less frequent control drug until the end of accrual
Overall Study Non-treatment-related AE	8	8
Overall Study Progressive disease	152	135
Overall Study Death	11	3
Overall Study Physician Decision	8	17
Overall Study Other reason not specified	3	1
Overall Study Symptomatic deterioration	13	19
Overall Study Treatment-related AE	10	14
Overall Study Withdrawal by Subject	14	16
Overall Study Not treated	2	8

Baseline Characteristics

Clinical Trial of Lurbinectedin (PM01183) in Platinum Resistant Ovarian Cancer Patients

Baseline characteristics by cohort

Measure	Lurbinectedin n=221 Participants 3.2 mg/m2 i.v. as a 1-hour infusion on Day 1 q3wk (three weeks = one treatment cycle) through peripheral or central lines. A minimum total volume of 100 mL, diluted in 5% glucose or 0.9% sodium chloride solution for infusion, had to be used for administration through a central venous catheter; if a peripheral venous catheter was used, the minimum volume was 250 mL	Control (PLD or Topotecan) n=221 Participants Patients randomized to the Control arm were assigned to receive PLD if they had previously been treated with topotecan, or to receive topotecan if they had previously been treated with PLD. However, if the number of patients randomized to either PLD or topotecan reached 60% (i.e., 126 patients) of the total number of patients expected in the Control Arm, then the treatment of choice in the Control Arm would be restricted to the less frequent control drug until the end of accrual	Total n=442 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	126 Participants n=5 Participants	141 Participants n=7 Participants	267 Participants n=5 Participants
Age, Categorical >=65 years	95 Participants n=5 Participants	80 Participants n=7 Participants	175 Participants n=5 Participants
Age, Continuous	63.0 years n=5 Participants	59.0 years n=7 Participants	61.0 years n=5 Participants
Sex: Female, Male Female	221 Participants n=5 Participants	221 Participants n=7 Participants	442 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) White	192 Participants n=5 Participants	201 Participants n=7 Participants	393 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	21 Participants n=5 Participants	14 Participants n=7 Participants	35 Participants n=5 Participants
Region of Enrollment United States	39 participants n=5 Participants	40 participants n=7 Participants	79 participants n=5 Participants
Region of Enrollment Romania	11 participants n=5 Participants	11 participants n=7 Participants	22 participants n=5 Participants
Region of Enrollment Spain	40 participants n=5 Participants	46 participants n=7 Participants	86 participants n=5 Participants
Region of Enrollment United Kingdom	17 participants n=5 Participants	14 participants n=7 Participants	31 participants n=5 Participants
Region of Enrollment Austria	3 participants n=5 Participants	4 participants n=7 Participants	7 participants n=5 Participants
Region of Enrollment Belgium	21 participants n=5 Participants	19 participants n=7 Participants	40 participants n=5 Participants
Region of Enrollment Bulgaria	5 participants n=5 Participants	5 participants n=7 Participants	10 participants n=5 Participants
Region of Enrollment Czechia	5 participants n=5 Participants	5 participants n=7 Participants	10 participants n=5 Participants
Region of Enrollment France	19 participants n=5 Participants	12 participants n=7 Participants	31 participants n=5 Participants
Region of Enrollment Hungary	9 participants n=5 Participants	14 participants n=7 Participants	23 participants n=5 Participants
Region of Enrollment Italy	47 participants n=5 Participants	47 participants n=7 Participants	94 participants n=5 Participants
Region of Enrollment Serbia	5 participants n=5 Participants	4 participants n=7 Participants	9 participants n=5 Participants
Body mass index ≤20 kg/m^2	26 Participants n=5 Participants	37 Participants n=7 Participants	63 Participants n=5 Participants
Body mass index 20-25 kg/m^2	82 Participants n=5 Participants	84 Participants n=7 Participants	166 Participants n=5 Participants
Body mass index 25-30 kg/m^2	62 Participants n=5 Participants	51 Participants n=7 Participants	113 Participants n=5 Participants
Body mass index >30 kg/m^2	50 Participants n=5 Participants	49 Participants n=7 Participants	99 Participants n=5 Participants
Body mass index Unknown	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
ECOG PS PS 0	126 Participants n=5 Participants	123 Participants n=7 Participants	249 Participants n=5 Participants
ECOG PS PS 1	87 Participants n=5 Participants	94 Participants n=7 Participants	181 Participants n=5 Participants
ECOG PS PS 2	8 Participants n=5 Participants	4 Participants n=7 Participants	12 Participants n=5 Participants
Primary site Ovarian	196 Participants n=5 Participants	195 Participants n=7 Participants	391 Participants n=5 Participants
Primary site Fallopian	11 Participants n=5 Participants	13 Participants n=7 Participants	24 Participants n=5 Participants
Primary site Peritoneal	14 Participants n=5 Participants	13 Participants n=7 Participants	27 Participants n=5 Participants
Histology type Serous/Papillary	181 Participants n=5 Participants	199 Participants n=7 Participants	380 Participants n=5 Participants
Histology type Endometrioid	14 Participants n=5 Participants	6 Participants n=7 Participants	20 Participants n=5 Participants
Histology type Clear cell	10 Participants n=5 Participants	12 Participants n=7 Participants	22 Participants n=5 Participants
Histology type Mucinous	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Histology type Other	13 Participants n=5 Participants	3 Participants n=7 Participants	16 Participants n=5 Participants
Histologic grade Well differentiated	16 Participants n=5 Participants	15 Participants n=7 Participants	31 Participants n=5 Participants
Histologic grade Moderately differentiated	21 Participants n=5 Participants	24 Participants n=7 Participants	45 Participants n=5 Participants
Histologic grade Poorly differentiated/Undifferentiated	154 Participants n=5 Participants	143 Participants n=7 Participants	297 Participants n=5 Participants
Histologic grade Unknown	30 Participants n=5 Participants	39 Participants n=7 Participants	69 Participants n=5 Participants
BRCA status BRCA1	10 Participants n=5 Participants	8 Participants n=7 Participants	18 Participants n=5 Participants
BRCA status BRCA2	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
BRCA status Not mutated	64 Participants n=5 Participants	61 Participants n=7 Participants	125 Participants n=5 Participants
BRCA status Unknown	143 Participants n=5 Participants	149 Participants n=7 Participants	292 Participants n=5 Participants
Intestinal sub-occlusion Yes	9 Participants n=5 Participants	10 Participants n=7 Participants	19 Participants n=5 Participants
Intestinal sub-occlusion No	212 Participants n=5 Participants	211 Participants n=7 Participants	423 Participants n=5 Participants
Clinically evident ascites Yes	35 Participants n=5 Participants	39 Participants n=7 Participants	74 Participants n=5 Participants
Clinically evident ascites No	186 Participants n=5 Participants	182 Participants n=7 Participants	368 Participants n=5 Participants
Radiological presence of ascites Yes	59 Participants n=5 Participants	71 Participants n=7 Participants	130 Participants n=5 Participants
Radiological presence of ascites No	162 Participants n=5 Participants	150 Participants n=7 Participants	312 Participants n=5 Participants
Prior radiotherapy Yes	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Prior radiotherapy No	215 Participants n=5 Participants	216 Participants n=7 Participants	431 Participants n=5 Participants
Prior Cytoreductive surgery Yes	198 Participants n=5 Participants	204 Participants n=7 Participants	402 Participants n=5 Participants
Prior Cytoreductive surgery No	23 Participants n=5 Participants	17 Participants n=7 Participants	40 Participants n=5 Participants
Other prior surgical procedures Yes	86 Participants n=5 Participants	81 Participants n=7 Participants	167 Participants n=5 Participants
Other prior surgical procedures No	135 Participants n=5 Participants	140 Participants n=7 Participants	275 Participants n=5 Participants
Weight	65.8 Kg n=5 Participants	63.0 Kg n=7 Participants	64.4 Kg n=5 Participants
Height	161.0 cm n=5 Participants	161.0 cm n=7 Participants	161.0 cm n=5 Participants
Body Surface Area	1.7 m^2 n=5 Participants	1.7 m^2 n=7 Participants	1.7 m^2 n=5 Participants
Body mass index	25.1 kg/m^2 n=5 Participants	24.7 kg/m^2 n=7 Participants	24.9 kg/m^2 n=5 Participants
First diagnosis to randomization	23.4 months n=5 Participants	20.7 months n=7 Participants	22.05 months n=5 Participants
Sites involved	2.0 number of sites n=5 Participants	2.0 number of sites n=7 Participants	2.0 number of sites n=5 Participants

PRIMARY outcome

Timeframe: Time from the date of randomization to the date of PD, death (of any cause), or last tumor evaluation, whichever came first, assessed up to 3 years

The primary endpoint was PFS by IRC assessment, defined as the time from the date of randomization to the date of documented progression per RECIST v.1.1 or death (regardless of the cause of death). If the patient received further antitumor therapy or was lost to follow-up before PD, PFS was censored at the date of last tumor assessment before the date of subsequent antitumor treatment.

Outcome measures

Measure	Lurbinectedin n=221 Participants 3.2 mg/m2 i.v. as a 1-hour infusion on Day 1 q3wk (three weeks = one treatment cycle) through peripheral or central lines. A minimum total volume of 100 mL, diluted in 5% glucose or 0.9% sodium chloride solution for infusion, had to be used for administration through a central venous catheter; if a peripheral venous catheter was used, the minimum volume was 250 mL	Control (PLD or Topotecan) n=221 Participants Patients randomized to the Control arm were assigned to receive PLD if they had previously been treated with topotecan, or to receive topotecan if they had previously been treated with PLD. However, if the number of patients randomized to either PLD or topotecan reached 60% (i.e., 126 patients) of the total number of patients expected in the Control Arm, then the treatment of choice in the Control Arm would be restricted to the less frequent control drug until the end of accrual
Progression-free Survival by Independent Review Committee	3.5 months Interval 2.1 to 3.7	3.6 months Interval 2.7 to 3.8

SECONDARY outcome

Timeframe: Time from the date of randomization to the date of PD, death (of any cause), or last tumor evaluation, whichever came first, assessed up to 3 years

The primary endpoint was PFS by Investigator's Assessment, defined as the time from the date of randomization to the date of documented progression per RECIST v.1.1 or death (regardless of the cause of death). If the patient received further antitumor therapy or was lost to follow-up before PD, PFS was censored at the date of last tumor assessment before the date of subsequent antitumor treatment.

Outcome measures

Measure	Lurbinectedin n=221 Participants 3.2 mg/m2 i.v. as a 1-hour infusion on Day 1 q3wk (three weeks = one treatment cycle) through peripheral or central lines. A minimum total volume of 100 mL, diluted in 5% glucose or 0.9% sodium chloride solution for infusion, had to be used for administration through a central venous catheter; if a peripheral venous catheter was used, the minimum volume was 250 mL	Control (PLD or Topotecan) n=221 Participants Patients randomized to the Control arm were assigned to receive PLD if they had previously been treated with topotecan, or to receive topotecan if they had previously been treated with PLD. However, if the number of patients randomized to either PLD or topotecan reached 60% (i.e., 126 patients) of the total number of patients expected in the Control Arm, then the treatment of choice in the Control Arm would be restricted to the less frequent control drug until the end of accrual
Progression-free Survival by Investigator's Assessment	3.7 months Interval 3.6 to 3.9	3.7 months Interval 3.5 to 4.0

SECONDARY outcome

Timeframe: From the date of randomization to the date of death or last contact, up to 12 months after last patient inclusion, for a maximum of up to 3 years

Calculated from the date of randomization to the date of death (death event) or last contact (in this case, survival was censored on that date).

Outcome measures

Measure	Lurbinectedin n=221 Participants 3.2 mg/m2 i.v. as a 1-hour infusion on Day 1 q3wk (three weeks = one treatment cycle) through peripheral or central lines. A minimum total volume of 100 mL, diluted in 5% glucose or 0.9% sodium chloride solution for infusion, had to be used for administration through a central venous catheter; if a peripheral venous catheter was used, the minimum volume was 250 mL	Control (PLD or Topotecan) n=221 Participants Patients randomized to the Control arm were assigned to receive PLD if they had previously been treated with topotecan, or to receive topotecan if they had previously been treated with PLD. However, if the number of patients randomized to either PLD or topotecan reached 60% (i.e., 126 patients) of the total number of patients expected in the Control Arm, then the treatment of choice in the Control Arm would be restricted to the less frequent control drug until the end of accrual
Overall Survival (OS)	11.4 months Interval 9.0 to 14.2	10.9 months Interval 9.3 to 12.5

SECONDARY outcome

Timeframe: At baseline and every eight weeks from randomization until evidence of PD, assessed up to 3 years

Best antitumor response defined as the best response obtained according to RECIST v.1.1. Tumor assessment were performed at baseline and every 8 weeks from randomization until evidence of PD. Patients who discontinued treatment without PD continued with assessments.

Antitumor activity was assessed using the RECIST v.1.1 by the appropriate method [computed tomography scan or magnetic resonance imaging]: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters; Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum; Overall Response (OR)=CR+PR.

Outcome measures

Measure	Lurbinectedin n=221 Participants 3.2 mg/m2 i.v. as a 1-hour infusion on Day 1 q3wk (three weeks = one treatment cycle) through peripheral or central lines. A minimum total volume of 100 mL, diluted in 5% glucose or 0.9% sodium chloride solution for infusion, had to be used for administration through a central venous catheter; if a peripheral venous catheter was used, the minimum volume was 250 mL	Control (PLD or Topotecan) n=221 Participants Patients randomized to the Control arm were assigned to receive PLD if they had previously been treated with topotecan, or to receive topotecan if they had previously been treated with PLD. However, if the number of patients randomized to either PLD or topotecan reached 60% (i.e., 126 patients) of the total number of patients expected in the Control Arm, then the treatment of choice in the Control Arm would be restricted to the less frequent control drug until the end of accrual
Overall Response Rate (ORR) by Independent Review Committee Complete response	3 Participants	3 Participants
Overall Response Rate (ORR) by Independent Review Committee Partial response	29 Participants	25 Participants
Overall Response Rate (ORR) by Independent Review Committee Stable disease	90 Participants	97 Participants
Overall Response Rate (ORR) by Independent Review Committee Progressive disease	83 Participants	72 Participants
Overall Response Rate (ORR) by Independent Review Committee Unknown	16 Participants	24 Participants

SECONDARY outcome

Timeframe: At baseline and every eight weeks from randomization until evidence of PD, assessed up to 3 years

Best antitumor response defined as the best response obtained according to RECIST v.1.1. Tumor assessment were performed at baseline and every 8 weeks from randomization until evidence of PD. Patients who discontinued treatment without PD continued with assessments.

Antitumor activity was assessed using the RECIST v.1.1 by the appropriate method [computed tomography scan or magnetic resonance imaging]: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters; Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum; Overall Response (OR)=CR+PR.

Outcome measures

Measure	Lurbinectedin n=221 Participants 3.2 mg/m2 i.v. as a 1-hour infusion on Day 1 q3wk (three weeks = one treatment cycle) through peripheral or central lines. A minimum total volume of 100 mL, diluted in 5% glucose or 0.9% sodium chloride solution for infusion, had to be used for administration through a central venous catheter; if a peripheral venous catheter was used, the minimum volume was 250 mL	Control (PLD or Topotecan) n=221 Participants Patients randomized to the Control arm were assigned to receive PLD if they had previously been treated with topotecan, or to receive topotecan if they had previously been treated with PLD. However, if the number of patients randomized to either PLD or topotecan reached 60% (i.e., 126 patients) of the total number of patients expected in the Control Arm, then the treatment of choice in the Control Arm would be restricted to the less frequent control drug until the end of accrual
Overall Response Rate by Investigator's Assessment Complete response	3 Participants	2 Participants
Overall Response Rate by Investigator's Assessment Partial response	32 Participants	35 Participants
Overall Response Rate by Investigator's Assessment Stable disease	107 Participants	94 Participants
Overall Response Rate by Investigator's Assessment Progressive disease	63 Participants	68 Participants
Overall Response Rate by Investigator's Assessment Unknown	16 Participants	22 Participants

SECONDARY outcome

Timeframe: The time from the date when the response criteria (PR or CR, whichever was reached first) were fulfilled, to the first date when PD, recurrence or death was documented, up to 3 years

Population: Patients who have CR or PR

Duration of response (DR): calculated from the date of first documentation of response per RECIST v.1.1 (CR or PR, whichever came first) to the date of documented PD or death. The censoring rules defined above for PFS were used for duration of response.

Best antitumor response defined as the best response obtained according to RECIST v.1.1. Tumor assessment were performed at baseline and every 8 weeks from randomization until evidence of PD. Patients who discontinued treatment without PD continued with assessments.

Antitumor activity was assessed using the RECIST v.1.1 by the appropriate method [computed tomography scan or magnetic resonance imaging]: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR)=CR+PR.

Outcome measures

Measure	Lurbinectedin n=32 Participants 3.2 mg/m2 i.v. as a 1-hour infusion on Day 1 q3wk (three weeks = one treatment cycle) through peripheral or central lines. A minimum total volume of 100 mL, diluted in 5% glucose or 0.9% sodium chloride solution for infusion, had to be used for administration through a central venous catheter; if a peripheral venous catheter was used, the minimum volume was 250 mL	Control (PLD or Topotecan) n=28 Participants Patients randomized to the Control arm were assigned to receive PLD if they had previously been treated with topotecan, or to receive topotecan if they had previously been treated with PLD. However, if the number of patients randomized to either PLD or topotecan reached 60% (i.e., 126 patients) of the total number of patients expected in the Control Arm, then the treatment of choice in the Control Arm would be restricted to the less frequent control drug until the end of accrual
Duration of Response by Independent Review Committee	4.0 months Interval 1.9 to 5.7	3.7 months Interval 3.6 to 7.2

SECONDARY outcome

Timeframe: The time from the date when the response criteria (PR or CR, whichever was reached first) were fulfilled, to the first date when PD, recurrence or death was documented, up to 3 years

Population: Patients who have CR or PR

Duration of response (DR): calculated from the date of first documentation of response per RECIST v.1.1 (CR or PR, whichever came first) to the date of documented PD or death. The censoring rules defined above for PFS were used for duration of response.

Best antitumor response defined as the best response obtained according to RECIST v.1.1. Tumor assessment were performed at baseline and every 8 weeks from randomization until evidence of PD. Patients who discontinued treatment without PD continued with assessments.

Antitumor activity was assessed using the RECIST v.1.1 by the appropriate method [computed tomography scan or magnetic resonance imaging]: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR)=CR+PR.

Outcome measures

Measure	Lurbinectedin n=35 Participants 3.2 mg/m2 i.v. as a 1-hour infusion on Day 1 q3wk (three weeks = one treatment cycle) through peripheral or central lines. A minimum total volume of 100 mL, diluted in 5% glucose or 0.9% sodium chloride solution for infusion, had to be used for administration through a central venous catheter; if a peripheral venous catheter was used, the minimum volume was 250 mL	Control (PLD or Topotecan) n=37 Participants Patients randomized to the Control arm were assigned to receive PLD if they had previously been treated with topotecan, or to receive topotecan if they had previously been treated with PLD. However, if the number of patients randomized to either PLD or topotecan reached 60% (i.e., 126 patients) of the total number of patients expected in the Control Arm, then the treatment of choice in the Control Arm would be restricted to the less frequent control drug until the end of accrual
Duration of Response by Investigator's Assessment	4.3 months Interval 3.6 to 5.8	3.7 months Interval 3.2 to 5.6

SECONDARY outcome

Timeframe: At baseline and every eight weeks from randomization until evidence of PD, up to 3 years

Best response according to tumor marker evaluation (CA-125): defined as the best response obtained according to GCIG criteria. Tumor marker assessments were performed at baseline and every eight weeks from randomization until evidence of PD. Progression based on serum CA-125 levels was defined on the basis of a progressive serial elevation of serum CA-125 according to:

A. Patients with elevated CA-125 pretreatment and normalization of CA-125 must show evidence of CA-125 greater than, or equal to, 2 times the upper limit of the reference range on 2 occasions at least 1 week apart or B. Patients with elevated CA-125 before treatment, which never normalizes, must show evidence of CA-125 greater than, or equal to, 2 times the nadir value on 2 occasions at least 1 week apart or C. Patients with CA-125 in the reference range before treatment must show evidence of CA-125 greater than, or equal to, 2 times the upper limit of the reference range on 2 occasions at least 1 week apart.

Outcome measures

Measure	Lurbinectedin n=173 Participants 3.2 mg/m2 i.v. as a 1-hour infusion on Day 1 q3wk (three weeks = one treatment cycle) through peripheral or central lines. A minimum total volume of 100 mL, diluted in 5% glucose or 0.9% sodium chloride solution for infusion, had to be used for administration through a central venous catheter; if a peripheral venous catheter was used, the minimum volume was 250 mL	Control (PLD or Topotecan) n=165 Participants Patients randomized to the Control arm were assigned to receive PLD if they had previously been treated with topotecan, or to receive topotecan if they had previously been treated with PLD. However, if the number of patients randomized to either PLD or topotecan reached 60% (i.e., 126 patients) of the total number of patients expected in the Control Arm, then the treatment of choice in the Control Arm would be restricted to the less frequent control drug until the end of accrual
Best Response According to Tumor Marker Evaluation (CA-125) Complete response	13 Participants	3 Participants
Best Response According to Tumor Marker Evaluation (CA-125) Partial response	33 Participants	29 Participants
Best Response According to Tumor Marker Evaluation (CA-125) Stable disease	95 Participants	94 Participants
Best Response According to Tumor Marker Evaluation (CA-125) Progressive disease	17 Participants	16 Participants
Best Response According to Tumor Marker Evaluation (CA-125) Unknown	15 Participants	23 Participants

Adverse Events

Lurbinectedin

Serious events: 92 serious events

Other events: 212 other events

Deaths: 170 deaths

Control (PLD or Topotecan)

Serious events: 85 serious events

Other events: 211 other events

Deaths: 171 deaths

Serious adverse events

Measure	Lurbinectedin n=219 participants at risk 3.2 mg/m2 i.v. as a 1-hour infusion on Day 1 q3wk (three weeks = one treatment cycle) through peripheral or central lines. A minimum total volume of 100 mL, diluted in 5% glucose or 0.9% sodium chloride solution for infusion, had to be used for administration through a central venous catheter; if a peripheral venous catheter was used, the minimum volume was 250 mL	Control (PLD or Topotecan) n=213 participants at risk Patients randomized to the Control arm were assigned to receive PLD if they had previously been treated with topotecan, or to receive topotecan if they had previously been treated with PLD. However, if the number of patients randomized to either PLD or topotecan reached 60% (i.e., 126 patients) of the total number of patients expected in the Control Arm, then the treatment of choice in the Control Arm would be restricted to the less frequent control drug until the end of accrual
Vascular disorders Embolism	0.91% 2/219 • Number of events 2 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.47% 1/213 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Vascular disorders Phlebitis	0.46% 1/219 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.47% 1/213 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Vascular disorders Venous thrombosis	0.91% 2/219 • Number of events 2 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.47% 1/213 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Immune system disorders Hypersensitivity	0.00% 0/219 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.47% 1/213 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
General disorders Fatigue	0.91% 2/219 • Number of events 3 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.94% 2/213 • Number of events 2 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
General disorders General physical health deterioration	0.46% 1/219 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	1.9% 4/213 • Number of events 5 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
General disorders Influenza like illness	0.46% 1/219 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.47% 1/213 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
General disorders Pyrexia	1.4% 3/219 • Number of events 3 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.47% 1/213 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
General disorders Vessel puncture site haematoma	0.46% 1/219 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.00% 0/213 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
General disorders Chest pain	0.00% 0/219 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.47% 1/213 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
General disorders Malaise	0.00% 0/219 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.47% 1/213 • Number of events 2 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
General disorders Mucosal inflammation	0.00% 0/219 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	1.4% 3/213 • Number of events 4 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
General disorders Pain	0.00% 0/219 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.47% 1/213 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Injury, poisoning and procedural complications Subdural haematoma	0.46% 1/219 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.00% 0/213 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Injury, poisoning and procedural complications Toxicity to various agents	0.46% 1/219 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.00% 0/213 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Injury, poisoning and procedural complications Femur fracture	0.00% 0/219 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.47% 1/213 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Injury, poisoning and procedural complications Gastrointestinal stoma complication	0.00% 0/219 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.47% 1/213 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Injury, poisoning and procedural complications Transfusion reaction	0.00% 0/219 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.47% 1/213 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Investigations Alanine aminotransferase increased	0.46% 1/219 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.00% 0/213 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Investigations Blood creatinine increased	1.4% 3/219 • Number of events 3 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.00% 0/213 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Investigations Gamma-glutamyltransferase increased	0.46% 1/219 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.00% 0/213 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Investigations Transaminases increased	0.46% 1/219 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.00% 0/213 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Cardiac disorders Cardiac failure	0.46% 1/219 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.00% 0/213 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Cardiac disorders Cardiorespiratory arrest	1.4% 3/219 • Number of events 3 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.00% 0/213 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Cardiac disorders Coronary artery disease	0.46% 1/219 • Number of events 3 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.00% 0/213 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Cardiac disorders Myocardial infarction	0.46% 1/219 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.47% 1/213 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Cardiac disorders Atrial fibrillation	0.00% 0/219 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.47% 1/213 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Cardiac disorders Cardiac tamponade	0.00% 0/219 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.47% 1/213 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Blood and lymphatic system disorders Anaemia	3.7% 8/219 • Number of events 14 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	5.6% 12/213 • Number of events 19 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Blood and lymphatic system disorders Febrile neutropenia	6.4% 14/219 • Number of events 14 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	5.6% 12/213 • Number of events 13 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Blood and lymphatic system disorders Leucopenia	1.4% 3/219 • Number of events 3 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	1.4% 3/213 • Number of events 4 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Blood and lymphatic system disorders Neutropenia	5.0% 11/219 • Number of events 14 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	6.1% 13/213 • Number of events 14 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Blood and lymphatic system disorders Thrombocytopenia	4.1% 9/219 • Number of events 9 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	5.2% 11/213 • Number of events 20 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Blood and lymphatic system disorders Leukocytosis	0.00% 0/219 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.47% 1/213 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.91% 2/219 • Number of events 2 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	1.9% 4/213 • Number of events 5 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Respiratory, thoracic and mediastinal disorders Lung disorder	0.46% 1/219 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.00% 0/213 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.4% 3/219 • Number of events 3 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	1.4% 3/213 • Number of events 5 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.4% 3/219 • Number of events 3 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	1.4% 3/213 • Number of events 3 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.46% 1/219 • Number of events 2 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.00% 0/213 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/219 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.47% 1/213 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/219 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.47% 1/213 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Nervous system disorders Cerebrovascular accident	0.91% 2/219 • Number of events 2 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.47% 1/213 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Nervous system disorders Hypoglycaemic coma	0.46% 1/219 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.00% 0/213 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Nervous system disorders Paresis	0.46% 1/219 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.00% 0/213 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Nervous system disorders Toxic encephalopathy	0.46% 1/219 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.00% 0/213 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Nervous system disorders Neuropathy peripheral	0.00% 0/219 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.47% 1/213 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Gastrointestinal disorders Abdominal distension	0.91% 2/219 • Number of events 2 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.00% 0/213 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Gastrointestinal disorders Abdominal pain	2.7% 6/219 • Number of events 8 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	2.8% 6/213 • Number of events 6 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Gastrointestinal disorders Ascites	1.8% 4/219 • Number of events 6 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	3.3% 7/213 • Number of events 11 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Gastrointestinal disorders Constipation	0.91% 2/219 • Number of events 2 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.00% 0/213 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Gastrointestinal disorders Diarrhoea	0.91% 2/219 • Number of events 2 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.94% 2/213 • Number of events 2 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Gastrointestinal disorders Intestinal obstruction	11.0% 24/219 • Number of events 32 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	9.9% 21/213 • Number of events 28 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Gastrointestinal disorders Intestinal perforation	0.46% 1/219 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.47% 1/213 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Gastrointestinal disorders Nausea	3.2% 7/219 • Number of events 8 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	1.9% 4/213 • Number of events 5 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Gastrointestinal disorders Oesophageal stenosis	0.46% 1/219 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.00% 0/213 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Gastrointestinal disorders Proctalgia	0.46% 1/219 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.00% 0/213 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Gastrointestinal disorders Vomiting	4.6% 10/219 • Number of events 10 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	1.9% 4/213 • Number of events 5 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/219 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.47% 1/213 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Gastrointestinal disorders Neutropenic colitis	0.00% 0/219 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	1.4% 3/213 • Number of events 3 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Gastrointestinal disorders Oesophageal ulcer	0.00% 0/219 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.47% 1/213 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Gastrointestinal disorders Oesophagitis	0.00% 0/219 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.47% 1/213 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Hepatobiliary disorders Bile duct obstruction	0.46% 1/219 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.00% 0/213 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Hepatobiliary disorders Cholangitis	0.46% 1/219 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.00% 0/213 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Hepatobiliary disorders Cholecystitis	0.91% 2/219 • Number of events 2 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.00% 0/213 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Hepatobiliary disorders Portal vein thrombosis	0.46% 1/219 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.00% 0/213 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Renal and urinary disorders Haematuria	0.46% 1/219 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.47% 1/213 • Number of events 2 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Renal and urinary disorders Acute kidney injury	0.00% 0/219 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.47% 1/213 • Number of events 2 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Renal and urinary disorders Hydronephrosis	0.00% 0/219 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.47% 1/213 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/219 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.47% 1/213 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Metabolism and nutrition disorders Dehydration	1.8% 4/219 • Number of events 4 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.94% 2/213 • Number of events 2 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Metabolism and nutrition disorders Hyperclycemia	0.46% 1/219 • Number of events 2 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.00% 0/213 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Metabolism and nutrition disorders Hypoalbuminemia	0.46% 1/219 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.00% 0/213 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Metabolism and nutrition disorders Hypokalaemia	0.46% 1/219 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.94% 2/213 • Number of events 2 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Metabolism and nutrition disorders Hyponatraemia	0.91% 2/219 • Number of events 3 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.47% 1/213 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Metabolism and nutrition disorders Malnutrition	0.46% 1/219 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.00% 0/213 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Infections and infestations Abdominal wall abscess	0.46% 1/219 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.00% 0/213 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Infections and infestations Atypical pneumonia	0.46% 1/219 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.00% 0/213 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Infections and infestations Bacteraemia	0.46% 1/219 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.00% 0/213 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Infections and infestations Gastroenteritis	0.46% 1/219 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.00% 0/213 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Infections and infestations Herpes virus infection	0.46% 1/219 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.00% 0/213 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Infections and infestations Neutropenic sepsis	0.91% 2/219 • Number of events 2 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.00% 0/213 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Infections and infestations Pneumonia	0.91% 2/219 • Number of events 2 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.00% 0/213 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Infections and infestations Sepsis	2.3% 5/219 • Number of events 5 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.47% 1/213 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Infections and infestations Septic shock	0.46% 1/219 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.94% 2/213 • Number of events 2 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Infections and infestations Skin infection	0.46% 1/219 • Number of events 3 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.00% 0/213 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Infections and infestations Urinary tract infection	1.8% 4/219 • Number of events 4 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	1.4% 3/213 • Number of events 3 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Infections and infestations Infection	0.00% 0/219 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.94% 2/213 • Number of events 2 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Infections and infestations Influenza	0.00% 0/219 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.47% 1/213 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Infections and infestations Peritonitis	0.00% 0/219 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.47% 1/213 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplastic syndrome	0.46% 1/219 • Number of events 1 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	0.00% 0/213 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).

Other adverse events

Measure	Lurbinectedin n=219 participants at risk 3.2 mg/m2 i.v. as a 1-hour infusion on Day 1 q3wk (three weeks = one treatment cycle) through peripheral or central lines. A minimum total volume of 100 mL, diluted in 5% glucose or 0.9% sodium chloride solution for infusion, had to be used for administration through a central venous catheter; if a peripheral venous catheter was used, the minimum volume was 250 mL	Control (PLD or Topotecan) n=213 participants at risk Patients randomized to the Control arm were assigned to receive PLD if they had previously been treated with topotecan, or to receive topotecan if they had previously been treated with PLD. However, if the number of patients randomized to either PLD or topotecan reached 60% (i.e., 126 patients) of the total number of patients expected in the Control Arm, then the treatment of choice in the Control Arm would be restricted to the less frequent control drug until the end of accrual
Vascular disorders Hypertension	5.5% 12/219 • Number of events 22 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	1.9% 4/213 • Number of events 9 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Investigations Weight decreased	4.6% 10/219 • Number of events 14 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	6.6% 14/213 • Number of events 16 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Respiratory, thoracic and mediastinal disorders Cough	7.8% 17/219 • Number of events 19 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	12.2% 26/213 • Number of events 33 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Respiratory, thoracic and mediastinal disorders Dyspnoea	13.2% 29/219 • Number of events 37 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	10.8% 23/213 • Number of events 34 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Blood and lymphatic system disorders Anaemia	26.0% 57/219 • Number of events 155 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	36.2% 77/213 • Number of events 201 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Blood and lymphatic system disorders Leucopenia	10.5% 23/219 • Number of events 39 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	9.9% 21/213 • Number of events 38 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Blood and lymphatic system disorders Neutropenia	33.3% 73/219 • Number of events 167 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	41.8% 89/213 • Number of events 211 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Blood and lymphatic system disorders Thrombocytopenia	9.1% 20/219 • Number of events 46 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	18.3% 39/213 • Number of events 77 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Nervous system disorders Headache	11.9% 26/219 • Number of events 36 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	4.2% 9/213 • Number of events 10 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Nervous system disorders Neuropathy peripheral	8.7% 19/219 • Number of events 32 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	7.0% 15/213 • Number of events 20 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
General disorders Fatigue	60.7% 133/219 • Number of events 328 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	53.1% 113/213 • Number of events 206 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
General disorders Mucosal inflammation	10.0% 22/219 • Number of events 26 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	31.9% 68/213 • Number of events 145 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
General disorders Oedema	11.4% 25/219 • Number of events 32 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	6.1% 13/213 • Number of events 15 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
General disorders Pyrexia	11.4% 25/219 • Number of events 29 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	15.5% 33/213 • Number of events 40 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Psychiatric disorders Sleep disorder	10.0% 22/219 • Number of events 23 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	4.7% 10/213 • Number of events 10 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Gastrointestinal disorders Abdominal distension	5.5% 12/219 • Number of events 16 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	4.7% 10/213 • Number of events 12 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Gastrointestinal disorders Abdominal pain	33.8% 74/219 • Number of events 145 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	24.4% 52/213 • Number of events 73 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Gastrointestinal disorders Ascites	6.4% 14/219 • Number of events 15 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	9.9% 21/213 • Number of events 43 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Gastrointestinal disorders Constipation	32.9% 72/219 • Number of events 118 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	28.6% 61/213 • Number of events 84 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Gastrointestinal disorders Diarrhoea	20.5% 45/219 • Number of events 71 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	16.4% 35/213 • Number of events 58 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Gastrointestinal disorders Nausea	71.2% 156/219 • Number of events 390 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	43.2% 92/213 • Number of events 169 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Gastrointestinal disorders Dyspepsia	6.4% 14/219 • Number of events 16 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	7.0% 15/213 • Number of events 16 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Gastrointestinal disorders Vomiting	39.7% 87/219 • Number of events 196 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	27.2% 58/213 • Number of events 88 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Skin and subcutaneous tissue disorders Alopecia	2.3% 5/219 • Number of events 5 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	14.1% 30/213 • Number of events 33 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	1.4% 3/219 • Number of events 3 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	23.9% 51/213 • Number of events 98 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Skin and subcutaneous tissue disorders Rash	3.7% 8/219 • Number of events 9 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	6.6% 14/213 • Number of events 25 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Musculoskeletal and connective tissue disorders Arthralgia	6.8% 15/219 • Number of events 20 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	2.3% 5/213 • Number of events 7 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Musculoskeletal and connective tissue disorders Back pain	5.9% 13/219 • Number of events 17 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	8.9% 19/213 • Number of events 22 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Metabolism and nutrition disorders Decreased appetite	23.3% 51/219 • Number of events 81 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	22.1% 47/213 • Number of events 69 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Metabolism and nutrition disorders Hypokalaemia	6.8% 15/219 • Number of events 26 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	7.0% 15/213 • Number of events 28 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Infections and infestations Upper respiratory tract infection	5.0% 11/219 • Number of events 14 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	9.4% 20/213 • Number of events 21 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).
Infections and infestations Urinary tract infection	9.6% 21/219 • Number of events 25 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).	7.0% 15/213 • Number of events 18 • Participants were assessed through study completion, approximately 3 years A total of 432 of 442 patients randomized in this study were treated (n=219 in the Lurbinectedin arm; n=213 in the Control arm \[PLD or topotecan\]) and therefore were evaluable for safety. Ten patients were not treated after randomization: two in the Lurbinectedin arm and eight in the Control arm (PLD or topotecan).

Additional Information

Pharma Mar S.A.

Pharma Mar S.A.

Phone: 0034918466000

Email: clinicaltrials@pharmamar.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60