Small-cell Lung Cancer
Conditions
Brief summary
Phase III randomized clinical trial of lurbinectedin (PM01183)/doxorubicin (DOX) versus cyclophosphamide (CTX), doxorubicin (DOX) and vincristine (VCR) (CAV) or topotecan as treatment in patients with small-cell lung cancer (SCLC) who failed one prior platinum-containing line.
Detailed description
Multicenter, open-label, randomized, controlled phase III clinical trial to evaluate and compare the activity and safety of an experimental arm consisting of PM01183/DOX combination followed by PM01183 alone, if applicable vs. best Investigator's choice between CAV or topotecan as a control arm, in SCLC patients who failed one prior platinum-containing line but no more than one prior chemotherapy-containing line.
Interventions
DRUGVincristine (VCR)
DRUGTopotecan
Sponsors
PharmaMar
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Voluntary written informed consent 2. Adult patients ≥ 18 years 3. Histologically or cytologically confirmed diagnosis of limited or extensive stage SCLC which failed one prior platinum-containing regimen and with a chemotherapy-free interval (CTFI, time from the last dose of first-line chemotherapy to the occurrence of progressive disease) ≥ 30 days. Small-cell carcinoma of unknown primary site with or without neuroendocrine features confirmed in histology test(s) performed on metastatic lesion(s) are eligible, if Ki-67/MIB-1 is expressed in \>50% of tumor cells. 4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 2. 5. Adequate hematological, renal, metabolic and hepatic function within 7-10 days prior to randomization 6. At least three weeks since last prior anticancer treatment and adequate recovery from prior treatment toxicity 7. Prior radiotherapy (RT): At least four weeks since completion of whole-brain irradiation, at least two weeks since completion of prophylactic cranial irradiation, and to any other site. 8. Evidence of non-childbearing status for women of childbearing potential (WOCBP). WOCBP must agree to use a highly effective contraceptive measure up to six weeks after treatment discontinuation. Fertile male patients with WOCBP partners should use condoms during treatment and for four months following the last investigational medicinal product dose.
Exclusion criteria
1. More than one prior chemotherapy-containing line(re-challenge with the same initial regimen is not allowed) 2. Patients who never received platinum-containing regimen for Small-cell Lung Cancer (SCLC) 3. Prior treatment with PM01183, topotecan or anthracyclines. 4. Limited-stage patients who are candidates for local or regional therapy 5. Impending need for palliative RT or surgery for pathological fractures and/or for medullary compression within four weeks prior to randomization. 6. Symptomatic or progressing or steroid requiring Central Nervous System (CNS) involvement disease at least four weeks prior to randomization 7. Concomitant diseases/conditions: Angina, myocardial infarction, congestive heart failure or clinically significant valvular heart disease, arrhythmia, immunodeficiency (including known HIV seropositive), ongoing or treatment-requiring chronic liver disease, active infection, oxygen requirement within two weeks prior to randomization, diffuse interstitial lung disease (ILD) or pulmonary fibrosis, second invasive malignancy treated with chemotherapy and/or radiotherapy, invasive fungal infections requiring systemic treatment within 12 weeks of randomization. 8. Pregnant or breast feeding women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Every three months up to death or study termination, a period of approximately 3.5 years | Overall survival (OS) will be calculated from the date of randomization to the date of death (death event) or last contact(in this case, survival will be censored on that date). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Overall Survival Between Lurbinectedin/DOX and CAV in Patients With CAV as Best Investigator's Choice: Overall Survival Rate at 18 Months | At 18 months | Overall survival (OS) will be calculated from the date of randomization to the date of death (death event) or last contact(in this case, survival will be censored on that date). |
| Difference in Overall Survival Between Lurbinectedin/DOX and CAV in Patients With CAV as Best Investigator's Choice: Overall Survival Rate at 24 Months | At 24 months | Overall survival (OS) will be calculated from the date of randomization to the date of death (death event) or last contact(in this case, survival will be censored on that date). |
| Progression-free Survival (PFS) by Independent Review Committee | Every six weeks up to progression disease, a period of approximately 3.5 years | Progression-free survival (PFS) is 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 receives further antitumor therapy or is lost to follow-up before PD, PFS will be censored at the date of last tumor assessment before the date of subsequent antitumor therapy. |
| Progression-free Survival Rate at 6 Months by Independent Review Committee | At 6 months | Progression-free survival (PFS) is 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 receives further antitumor therapy or is lost to follow-up before PD, PFS will be censored at the date of last tumor assessment before the date of subsequent antitumor therapy. |
| Progression-free Survival Rate at 12 Months by Independent Review Committee | at 12 months | Progression-free survival (PFS) is 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 receives further antitumor therapy or is lost to follow-up before PD, PFS will be censored at the date of last tumor assessment before the date of subsequent antitumor therapy. |
| Best Antitumor Response by Independent Review Committee | Every three months up to death or study termination, a period of approximately 3.5 years | Best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1. CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown |
| Overall Response Rate by Independent Review Committee | Every three months up to death or study termination, a period of approximately 3.5 years | Overall response rate is defined as the proportion of patients who have a partial or complete response in the best antitumor response. The best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1. CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown |
| Duration of Response by Independent Review Committee | Every three months up to death or study termination, a period of approximately 3.5 years | Duration of Response is defined as the time that patients who have a partial or complete response in the best antitumor response. The best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1. CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown |
| Overall Survival in Patients With Chemotherapy-free Interval ≥ 90 Days | Every three months up to death or study termination, a period of approximately 3.5 years | Overall survival (OS) will be calculated from the date of randomization to the date of death (death event) or last contact(in this case, survival will be censored on that date). |
| Progression-free Survival in Patients With Chemotherapy-free Interval ≥90 Days | Every six weeks up to progression disease, a period of approximately 3.5 years | Progression-free survival (PFS) is 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 receives further antitumor therapy or is lost to follow-up before PD, PFS will be censored at the date of last tumor assessment before the date of subsequent antitumor therapy. |
| Best Antitumor Response in Patients With Chemotherapy-free Interval ≥ 90 Days | Every three months up to death or study termination, a period of approximately 3.5 years | Best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1. CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown |
| Overall Response Rate in Patients With Chemotherapy-free Interval ≥ 90 Days | Every three months up to death or study termination, a period of approximately 3.5 years | Overall response rate is defined as the proportion of patients who have a partial or complete response in the best antitumor response. The best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1. CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown |
| Duration of Response in Patients With Chemotherapy-free Interval ≥ 90 Days | Every three months up to death or study termination, a period of approximately 3.5 years | Duration of Response is defined as the time that patients who have a partial or complete response in the best antitumor response. The best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1. CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown |
| Overall Survival in Patients With Chemotherapy-free Interval < 90 Days | Every three months up to death or study termination, a period of approximately 3.5 years | Overall survival (OS) will be calculated from the date of randomization to the date of death (death event) or last contact(in this case, survival will be censored on that date). |
| Difference in Overall Survival Between Lurbinectedin/Doxorubicin (DOX) and CAV in Patients With CAV as Best Investigator's Choice: Overall Survival Rate at 12 Months | At 12 months | Overall survival (OS) will be calculated from the date of randomization to the date of death (death event) or last contact(in this case, survival will be censored on that date). |
| Best Antitumor Response in Patients With Chemotherapy-free Interval <90 Days | Every three months up to death or study termination, a period of approximately 3.5 years | Best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1. CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown |
| Overall Response Rate in Patients With Chemotherapy-free Interval <90 Days | Every three months up to death or study termination, a period of approximately 3.5 years | Overall response rate is defined as the proportion of patients who have a partial or complete response in the best antitumor response. The best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1. CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown |
| Duration of Response in Patients With Chemotherapy-free Interval <90 Days | Every three months up to death or study termination, a period of approximately 3.5 years | Duration of Response is defined as the time that patients who have a partial or complete response in the best antitumor response. The best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1. CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown |
| Overall Survival in Patients Without Central Nervous System Involvement at Baseline | Every three months up to death or study termination, a period of approximately 3.5 years | Overall survival (OS) will be calculated from the date of randomization to the date of death (death event) or last contact(in this case, survival will be censored on that date). |
| Progression-free Survival in Patients Without Central Nervous System Involvement at Baseline | Every six weeks up to progression disease, a period of approximately 3.5 years | Progression-free survival (PFS) is 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 receives further antitumor therapy or is lost to follow-up before PD, PFS will be censored at the date of last tumor assessment before the date of subsequent antitumor therapy. |
| Best Antitumor Response in Patients Without Central Nervous System Involvement at Baseline | Every three months up to death or study termination, a period of approximately 3.5 years | Best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1. CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown |
| Overall Response Rate in Patients Without Central Nervous System Involvement at Baseline | Every three months up to death or study termination, a period of approximately 3.5 years | Overall response rate is defined as the proportion of patients who have a partial or complete response in the best antitumor response. The best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1. CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown |
| Duration of Response in Patients Without Central Nervous System Involvement at Baseline | Every three months up to death or study termination, a period of approximately 3.5 years | Duration of Response is defined as the time that patients who have a partial or complete response in the best antitumor response. The best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1. CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown |
| Overall Survival in Patients With Central Nervous System Involvement at Baseline | Every three months up to death or study termination, a period of approximately 3.5 years | Overall survival (OS) will be calculated from the date of randomization to the date of death (death event) or last contact(in this case, survival will be censored on that date). |
| Progression-free Survival in Patients With Central Nervous System Involvement at Baseline | Every six weeks up to progression disease, a period of approximately 3.5 years | Progression-free survival (PFS) is 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 receives further antitumor therapy or is lost to follow-up before PD, PFS will be censored at the date of last tumor assessment before the date of subsequent antitumor therapy. |
| Best Antitumor Response in Patients With Central Nervous System Involvement at Baseline | Every three months up to death or study termination, a period of approximately 3.5 years | Best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1. CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown |
| Overall Response Rate in Patients With Central Nervous System Involvement at Baseline | Every three months up to death or study termination, a period of approximately 3.5 years | Overall response rate is defined as the proportion of patients who have a partial or complete response in the best antitumor response. The best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1. CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown |
| Duration of Response in Patients With Central Nervous System Involvement at Baseline | Every three months up to death or study termination, a period of approximately 3.5 years | Duration of Response is defined as the time that patients who have a partial or complete response in the best antitumor response. The best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1. CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown |
| Progression-free Survival in Patients With Chemotherapy-free Interval <90 Days | Every six weeks up to progression disease, a period of approximately 3.5 years | Progression-free survival (PFS) is 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 receives further antitumor therapy or is lost to follow-up before PD, PFS will be censored at the date of last tumor assessment before the date of subsequent antitumor therapy. |
Countries
Argentina, Austria, Belgium, Brazil, Bulgaria, Canada, Czechia, France, Germany, Greece, Hungary, Italy, Lebanon, Netherlands, Poland, Portugal, Romania, Spain, United Kingdom, United States
Participant flow
Recruitment details
The first randomization took place on 30 August 2016 and the first study treatment was administered on 25 October 2016. The cutoff date for results presented in this Clinical Study Report was 24 February 2020. A total of 919 patients were screened; 613 of these 919 patients were randomized at a 1:1 ratio to receive any of the study treatments at 135 investigational sites from 20 countries.
Participants by arm
| Arm | Count |
|---|---|
| Lurbinectedin/Doxorubicin Doxorubicin: 40.0 mg/m2 i.v. on Day 1 through peripheral or central lines (according to local label), followed by, Lurbinectedin: 2.0 mg/m2 i.v. as a 1-hour infusion on Day 1 q3wk (three weeks ±48h = one treatment cycle) through peripheral or central lines. A minimum 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.
The combination was to be administered for up to a maximum of ten cycles. | 307 |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine If the patient was randomized to the Control Arm, the assigned treatment was based on the reported Investigator's preference between topotecan and CAV, until the first of these options had reached 55% of the target patient enrollment in this arm. Once this had occurred, patients in the Control Arm were to receive the other option.
Topotecan: i.v. daily on Days 1-5 q3wk (three weeks ±48h = one treatment cycle) through peripheral or central lines (according to local label) at the following doses:
* 1.50 mg/m2 daily, for patients with calculated CrCL ≥60 mL/min.
* 1.25 mg/m2 daily, for patients with calculated CrCL between 40 and 59 mL/min.
* 0.75 mg/m2 daily, for patients with calculated CrCL between 30 and 39 mL/min.
or
CAV: i.v. on Day 1 q3wk (three weeks ±48h = one treatment cycle) through peripheral or central lines at the following doses:
* Cyclophosphamide: 1000 mg/m2,
* Doxorubicin: 45.0 mg/m2,
* Vincristine: 2.0 mg flat dose. The triple combination was to be administered for up to a maximum of ten cycles | 306 |
| Total | 613 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 17 | 23 |
| Overall Study | End of study due to events required for OS analysis according to study protocol had been reached | 9 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Non study drug-related adverse event | 9 | 9 |
| Overall Study | Physician Decision | 10 | 17 |
| Overall Study | Progressive disease | 213 | 152 |
| Overall Study | Randomized but not treated | 5 | 16 |
| Overall Study | Screening failure | 2 | 0 |
| Overall Study | Sponsor's decision after incorrect treatment at site | 1 | 1 |
| Overall Study | Study drug-related adverse event | 20 | 41 |
| Overall Study | Symptomatic deterioration | 9 | 16 |
| Overall Study | Symptomatic deterioration, progression disease, and a decision by the Investigator | 0 | 1 |
| Overall Study | Withdrawal by Subject | 12 | 28 |
Baseline characteristics
| Characteristic | Lurbinectedin/Doxorubicin | Total | Topotecan or Cyclophosphamide/Doxorubicin/Vincristine |
|---|---|---|---|
| Age, Continuous | 63.0 years | 63 years | 63.0 years |
| Age, Customized 18-49 years | 16 Participants | 29 Participants | 13 Participants |
| Age, Customized 50-65 years | 161 Participants | 327 Participants | 166 Participants |
| Age, Customized >65 years | 130 Participants | 257 Participants | 127 Participants |
| Best response to last prior chemotherapy Complete response | 17 Participants | 32 Participants | 15 Participants |
| Best response to last prior chemotherapy Partial response | 192 Participants | 383 Participants | 191 Participants |
| Best response to last prior chemotherapy Progressive disease | 17 Participants | 38 Participants | 21 Participants |
| Best response to last prior chemotherapy Stable disease | 71 Participants | 134 Participants | 63 Participants |
| Best response to last prior chemotherapy Unknown | 10 Participants | 26 Participants | 16 Participants |
| Body mass index | 25.9 Kg/m^2 | 25.9 Kg/m^2 | 26.0 Kg/m^2 |
| Body surface area | 1.8 m^2 | 1.8 m^2 | 1.8 m^2 |
| Bulky disease | 144 Participants | 271 Participants | 127 Participants |
| Central Nervous System involvement | 46 Participants | 95 Participants | 49 Participants |
| Chemotherapy-free interval ≥180 days | 93 Participants | 182 Participants | 89 Participants |
| Chemotherapy-free interval 90-179 days | 115 Participants | 231 Participants | 116 Participants |
| Chemotherapy-free interval <90 days | 99 Participants | 200 Participants | 101 Participants |
| Chemotherapy-free interval | 115.0 days | 120 days | 120.5 days |
| Disease stage Extensive | 282 Participants | 560 Participants | 278 Participants |
| Disease stage Limited | 25 Participants | 53 Participants | 28 Participants |
| Eastern Cooperative Oncology Group Performance Status PS 0 | 95 Participants | 190 Participants | 95 Participants |
| Eastern Cooperative Oncology Group Performance Status PS 1 | 197 Participants | 401 Participants | 204 Participants |
| Eastern Cooperative Oncology Group Performance Status PS 2 | 15 Participants | 22 Participants | 7 Participants |
| Height | 168 cm | 168 cm | 168 cm |
| Lines of anticancer therapy | 1.0 lines of therapies | 1.0 lines of therapies | 1.0 lines of therapies |
| Number of sites involved <3 sites | 38 Participants | 69 Participants | 31 Participants |
| Number of sites involved ≥3 sites | 269 Participants | 544 Participants | 275 Participants |
| Number of sites involved | 4.0 sites | 4.0 sites | 4.0 sites |
| Paraneoplastic syndrome | 9 Participants | 20 Participants | 11 Participants |
| Prior immunotherapy against PD-1 or PD-L1 | 19 Participants | 36 Participants | 17 Participants |
| Prior radiotherapy | 237 Participants | 473 Participants | 236 Participants |
| Prior surgery | 27 Participants | 66 Participants | 39 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Not available | 38 Participants | 75 Participants | 37 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 4 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 266 Participants | 531 Participants | 265 Participants |
| Region of Enrollment Argentina | 3 Participants | 7 Participants | 4 Participants |
| Region of Enrollment Austria | 5 Participants | 8 Participants | 3 Participants |
| Region of Enrollment Belgium | 9 Participants | 21 Participants | 12 Participants |
| Region of Enrollment Brazil | 13 Participants | 28 Participants | 15 Participants |
| Region of Enrollment Bulgaria | 5 Participants | 11 Participants | 6 Participants |
| Region of Enrollment Canada | 10 Participants | 17 Participants | 7 Participants |
| Region of Enrollment Czechia | 4 Participants | 9 Participants | 5 Participants |
| Region of Enrollment France | 11 Participants | 23 Participants | 12 Participants |
| Region of Enrollment Germany | 33 Participants | 67 Participants | 34 Participants |
| Region of Enrollment Greece | 12 Participants | 25 Participants | 13 Participants |
| Region of Enrollment Hungary | 23 Participants | 46 Participants | 23 Participants |
| Region of Enrollment Italy | 21 Participants | 41 Participants | 20 Participants |
| Region of Enrollment Lebanon | 8 Participants | 17 Participants | 9 Participants |
| Region of Enrollment Netherlands | 9 Participants | 18 Participants | 9 Participants |
| Region of Enrollment Poland | 7 Participants | 13 Participants | 6 Participants |
| Region of Enrollment Portugal | 10 Participants | 15 Participants | 5 Participants |
| Region of Enrollment Romania | 20 Participants | 39 Participants | 19 Participants |
| Region of Enrollment Spain | 62 Participants | 125 Participants | 63 Participants |
| Region of Enrollment United Kingdom | 10 Participants | 21 Participants | 11 Participants |
| Region of Enrollment United States | 32 Participants | 62 Participants | 30 Participants |
| Sex: Female, Male Female | 131 Participants | 264 Participants | 133 Participants |
| Sex: Female, Male Male | 176 Participants | 349 Participants | 173 Participants |
| Smoking status Current | 91 Participants | 180 Participants | 89 Participants |
| Smoking status Former | 197 Participants | 396 Participants | 199 Participants |
| Smoking status Never | 19 Participants | 37 Participants | 18 Participants |
| Time from end date of last prior chemotherapy to randomization | 157.0 days | 155 days | 153.0 days |
| Time from first diagnosis to randomization | 9.3 months | 9.2 months | 9.1 months |
| Time from last prior progressive disease to randomization | 25.0 days | 25.0 days | 25.5 days |
| Time-to-progression to prior chemotherapy | 7.4 months | 7.4 months | 7.4 months |
| Weight | 73.0 Kg | 73.4 Kg | 74.0 Kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 264 / 303 | 100 / 121 | 148 / 168 |
| other Total, other adverse events | 292 / 303 | 120 / 121 | 148 / 168 |
| serious Total, serious adverse events | 126 / 303 | 66 / 121 | 75 / 168 |
Outcome results
Primary
Overall Survival (OS)
Overall survival (OS) will be calculated from the date of randomization to the date of death (death event) or last contact(in this case, survival will be censored on that date).
Time frame: Every three months up to death or study termination, a period of approximately 3.5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lurbinectedin/Doxorubicin | Overall Survival (OS) | 8.6 months |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Overall Survival (OS) | 7.6 months |
p-value: 0.902995% CI: [0.815, 1.148]Log Rank
Secondary
Best Antitumor Response by Independent Review Committee
Best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1. CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown
Time frame: Every three months up to death or study termination, a period of approximately 3.5 years
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lurbinectedin/Doxorubicin | Best Antitumor Response by Independent Review Committee | Partial response | 89 Participants |
| Lurbinectedin/Doxorubicin | Best Antitumor Response by Independent Review Committee | Progressive disease | 74 Participants |
| Lurbinectedin/Doxorubicin | Best Antitumor Response by Independent Review Committee | Stable disease | 111 Participants |
| Lurbinectedin/Doxorubicin | Best Antitumor Response by Independent Review Committee | Unknown | 25 Participants |
| Lurbinectedin/Doxorubicin | Best Antitumor Response by Independent Review Committee | Complete response | 8 Participants |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Best Antitumor Response by Independent Review Committee | Unknown | 47 Participants |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Best Antitumor Response by Independent Review Committee | Complete response | 4 Participants |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Best Antitumor Response by Independent Review Committee | Partial response | 87 Participants |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Best Antitumor Response by Independent Review Committee | Stable disease | 116 Participants |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Best Antitumor Response by Independent Review Committee | Progressive disease | 52 Participants |
Secondary
Best Antitumor Response in Patients With Central Nervous System Involvement at Baseline
Best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1. CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown
Time frame: Every three months up to death or study termination, a period of approximately 3.5 years
Population: A preplanned exploratory efficacy subgroup analysis was focused on patients with Central Nervous System Involvement at Baseline
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lurbinectedin/Doxorubicin | Best Antitumor Response in Patients With Central Nervous System Involvement at Baseline | Complete response | 1 Participants |
| Lurbinectedin/Doxorubicin | Best Antitumor Response in Patients With Central Nervous System Involvement at Baseline | Progression disease | 19 Participants |
| Lurbinectedin/Doxorubicin | Best Antitumor Response in Patients With Central Nervous System Involvement at Baseline | Stable disease | 10 Participants |
| Lurbinectedin/Doxorubicin | Best Antitumor Response in Patients With Central Nervous System Involvement at Baseline | Unknown | 6 Participants |
| Lurbinectedin/Doxorubicin | Best Antitumor Response in Patients With Central Nervous System Involvement at Baseline | Partial response | 10 Participants |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Best Antitumor Response in Patients With Central Nervous System Involvement at Baseline | Unknown | 9 Participants |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Best Antitumor Response in Patients With Central Nervous System Involvement at Baseline | Complete response | 1 Participants |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Best Antitumor Response in Patients With Central Nervous System Involvement at Baseline | Partial response | 11 Participants |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Best Antitumor Response in Patients With Central Nervous System Involvement at Baseline | Stable disease | 16 Participants |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Best Antitumor Response in Patients With Central Nervous System Involvement at Baseline | Progression disease | 12 Participants |
Secondary
Best Antitumor Response in Patients With Chemotherapy-free Interval <90 Days
Best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1. CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown
Time frame: Every three months up to death or study termination, a period of approximately 3.5 years
Population: A preplanned exploratory efficacy subgroup analysis was focused on patients had chemotherapy-free interval \<90 days after first-line chemotherapy
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lurbinectedin/Doxorubicin | Best Antitumor Response in Patients With Chemotherapy-free Interval <90 Days | Partial response | 20 Participants |
| Lurbinectedin/Doxorubicin | Best Antitumor Response in Patients With Chemotherapy-free Interval <90 Days | Stable disease | 26 Participants |
| Lurbinectedin/Doxorubicin | Best Antitumor Response in Patients With Chemotherapy-free Interval <90 Days | Progression disease | 42 Participants |
| Lurbinectedin/Doxorubicin | Best Antitumor Response in Patients With Chemotherapy-free Interval <90 Days | Unknown | 11 Participants |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Best Antitumor Response in Patients With Chemotherapy-free Interval <90 Days | Unknown | 22 Participants |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Best Antitumor Response in Patients With Chemotherapy-free Interval <90 Days | Partial response | 19 Participants |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Best Antitumor Response in Patients With Chemotherapy-free Interval <90 Days | Progression disease | 17 Participants |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Best Antitumor Response in Patients With Chemotherapy-free Interval <90 Days | Stable disease | 43 Participants |
Secondary
Best Antitumor Response in Patients With Chemotherapy-free Interval ≥ 90 Days
Best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1. CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown
Time frame: Every three months up to death or study termination, a period of approximately 3.5 years
Population: A preplanned exploratory efficacy subgroup analysis was focused on patients had chemotherapy-free interval ≥90 days after first-line chemotherapy
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lurbinectedin/Doxorubicin | Best Antitumor Response in Patients With Chemotherapy-free Interval ≥ 90 Days | Partial response | 69 Participants |
| Lurbinectedin/Doxorubicin | Best Antitumor Response in Patients With Chemotherapy-free Interval ≥ 90 Days | Progression disease | 32 Participants |
| Lurbinectedin/Doxorubicin | Best Antitumor Response in Patients With Chemotherapy-free Interval ≥ 90 Days | Stable disease | 85 Participants |
| Lurbinectedin/Doxorubicin | Best Antitumor Response in Patients With Chemotherapy-free Interval ≥ 90 Days | Unknown | 14 Participants |
| Lurbinectedin/Doxorubicin | Best Antitumor Response in Patients With Chemotherapy-free Interval ≥ 90 Days | Complete response | 8 Participants |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Best Antitumor Response in Patients With Chemotherapy-free Interval ≥ 90 Days | Unknown | 25 Participants |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Best Antitumor Response in Patients With Chemotherapy-free Interval ≥ 90 Days | Complete response | 4 Participants |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Best Antitumor Response in Patients With Chemotherapy-free Interval ≥ 90 Days | Partial response | 68 Participants |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Best Antitumor Response in Patients With Chemotherapy-free Interval ≥ 90 Days | Stable disease | 73 Participants |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Best Antitumor Response in Patients With Chemotherapy-free Interval ≥ 90 Days | Progression disease | 35 Participants |
Secondary
Best Antitumor Response in Patients Without Central Nervous System Involvement at Baseline
Best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1. CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown
Time frame: Every three months up to death or study termination, a period of approximately 3.5 years
Population: A preplanned exploratory efficacy subgroup analysis was focused on patients without Central Nervous System Involvement at Baseline
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lurbinectedin/Doxorubicin | Best Antitumor Response in Patients Without Central Nervous System Involvement at Baseline | Partial response | 79 Participants |
| Lurbinectedin/Doxorubicin | Best Antitumor Response in Patients Without Central Nervous System Involvement at Baseline | Progression disease | 55 Participants |
| Lurbinectedin/Doxorubicin | Best Antitumor Response in Patients Without Central Nervous System Involvement at Baseline | Stable disease | 101 Participants |
| Lurbinectedin/Doxorubicin | Best Antitumor Response in Patients Without Central Nervous System Involvement at Baseline | Unknown | 19 Participants |
| Lurbinectedin/Doxorubicin | Best Antitumor Response in Patients Without Central Nervous System Involvement at Baseline | Complete response | 7 Participants |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Best Antitumor Response in Patients Without Central Nervous System Involvement at Baseline | Unknown | 38 Participants |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Best Antitumor Response in Patients Without Central Nervous System Involvement at Baseline | Complete response | 3 Participants |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Best Antitumor Response in Patients Without Central Nervous System Involvement at Baseline | Partial response | 76 Participants |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Best Antitumor Response in Patients Without Central Nervous System Involvement at Baseline | Stable disease | 100 Participants |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Best Antitumor Response in Patients Without Central Nervous System Involvement at Baseline | Progression disease | 40 Participants |
Secondary
Difference in Overall Survival Between Lurbinectedin/DOX and CAV in Patients With CAV as Best Investigator's Choice: Overall Survival Rate at 18 Months
Overall survival (OS) will be calculated from the date of randomization to the date of death (death event) or last contact(in this case, survival will be censored on that date).
Time frame: At 18 months
Population: Patients with Cyclophosphamide, Doxorubicin and Vincristine (CAV) as best Investigator's choice
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lurbinectedin/Doxorubicin | Difference in Overall Survival Between Lurbinectedin/DOX and CAV in Patients With CAV as Best Investigator's Choice: Overall Survival Rate at 18 Months | 13.9 percentage of participants |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Difference in Overall Survival Between Lurbinectedin/DOX and CAV in Patients With CAV as Best Investigator's Choice: Overall Survival Rate at 18 Months | 15.9 percentage of participants |
p-value: 0.6216Normal test
Secondary
Difference in Overall Survival Between Lurbinectedin/DOX and CAV in Patients With CAV as Best Investigator's Choice: Overall Survival Rate at 24 Months
Overall survival (OS) will be calculated from the date of randomization to the date of death (death event) or last contact(in this case, survival will be censored on that date).
Time frame: At 24 months
Population: Patients with Cyclophosphamide, Doxorubicin and Vincristine (CAV) as best Investigator's choice
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lurbinectedin/Doxorubicin | Difference in Overall Survival Between Lurbinectedin/DOX and CAV in Patients With CAV as Best Investigator's Choice: Overall Survival Rate at 24 Months | 8.6 percentage of participants |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Difference in Overall Survival Between Lurbinectedin/DOX and CAV in Patients With CAV as Best Investigator's Choice: Overall Survival Rate at 24 Months | 8.7 percentage of participants |
p-value: 0.9708Normal test
Secondary
Difference in Overall Survival Between Lurbinectedin/Doxorubicin (DOX) and CAV in Patients With CAV as Best Investigator's Choice: Overall Survival Rate at 12 Months
Overall survival (OS) will be calculated from the date of randomization to the date of death (death event) or last contact(in this case, survival will be censored on that date).
Time frame: At 12 months
Population: Patients with Cyclophosphamide, Doxorubicin and Vincristine (CAV) as best Investigator's choice
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lurbinectedin/Doxorubicin | Difference in Overall Survival Between Lurbinectedin/Doxorubicin (DOX) and CAV in Patients With CAV as Best Investigator's Choice: Overall Survival Rate at 12 Months | 29.6 percentage of participants |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Difference in Overall Survival Between Lurbinectedin/Doxorubicin (DOX) and CAV in Patients With CAV as Best Investigator's Choice: Overall Survival Rate at 12 Months | 24.4 percentage of participants |
p-value: 0.2826Normal test
Secondary
Duration of Response by Independent Review Committee
Duration of Response is defined as the time that patients who have a partial or complete response in the best antitumor response. The best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1. CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown
Time frame: Every three months up to death or study termination, a period of approximately 3.5 years
Population: Patients who have a partial or complete response in the best antitumor response
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lurbinectedin/Doxorubicin | Duration of Response by Independent Review Committee | 5.7 months |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Duration of Response by Independent Review Committee | 3.8 months |
p-value: 0.001295% CI: [0.416, 0.812]Log Rank
Secondary
Duration of Response in Patients With Central Nervous System Involvement at Baseline
Duration of Response is defined as the time that patients who have a partial or complete response in the best antitumor response. The best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1. CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown
Time frame: Every three months up to death or study termination, a period of approximately 3.5 years
Population: Patients who have a partial or complete response in the best antitumor response. A preplanned exploratory efficacy subgroup analysis was focused on patients with Central Nervous System Involvement at Baseline
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lurbinectedin/Doxorubicin | Duration of Response in Patients With Central Nervous System Involvement at Baseline | 1.5 months |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Duration of Response in Patients With Central Nervous System Involvement at Baseline | 2.7 months |
95% CI: [0.373, 2.75]
Secondary
Duration of Response in Patients With Chemotherapy-free Interval <90 Days
Duration of Response is defined as the time that patients who have a partial or complete response in the best antitumor response. The best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1. CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown
Time frame: Every three months up to death or study termination, a period of approximately 3.5 years
Population: Patients who have a partial or complete response in the best antitumor response. A preplanned exploratory efficacy subgroup analysis was focused on patients had chemotherapy-free interval \<90 days after first-line chemotherapy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lurbinectedin/Doxorubicin | Duration of Response in Patients With Chemotherapy-free Interval <90 Days | 3.0 months |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Duration of Response in Patients With Chemotherapy-free Interval <90 Days | 2.8 months |
95% CI: [0.506, 2.36]
Secondary
Duration of Response in Patients With Chemotherapy-free Interval ≥ 90 Days
Duration of Response is defined as the time that patients who have a partial or complete response in the best antitumor response. The best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1. CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown
Time frame: Every three months up to death or study termination, a period of approximately 3.5 years
Population: Patients who have a partial or complete response in the best antitumor response. A preplanned exploratory efficacy subgroup analysis was focused on patients had chemotherapy-free interval ≥90 days after first-line chemotherapy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lurbinectedin/Doxorubicin | Duration of Response in Patients With Chemotherapy-free Interval ≥ 90 Days | 6.9 months |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Duration of Response in Patients With Chemotherapy-free Interval ≥ 90 Days | 4.0 months |
95% CI: [0.346, 0.736]
Secondary
Duration of Response in Patients Without Central Nervous System Involvement at Baseline
Duration of Response is defined as the time that patients who have a partial or complete response in the best antitumor response. The best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1. CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown
Time frame: Every three months up to death or study termination, a period of approximately 3.5 years
Population: Patients who have a partial or complete response in the best antitumor response. A preplanned exploratory efficacy subgroup analysis was focused on patients without Central Nervous System Involvement at Baseline
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lurbinectedin/Doxorubicin | Duration of Response in Patients Without Central Nervous System Involvement at Baseline | 5.7 months |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Duration of Response in Patients Without Central Nervous System Involvement at Baseline | 4.0 months |
95% CI: [0.392, 0.799]
Secondary
Overall Response Rate by Independent Review Committee
Overall response rate is defined as the proportion of patients who have a partial or complete response in the best antitumor response. The best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1. CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown
Time frame: Every three months up to death or study termination, a period of approximately 3.5 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lurbinectedin/Doxorubicin | Overall Response Rate by Independent Review Committee | 31.6 percentage of participants |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Overall Response Rate by Independent Review Committee | 29.7 percentage of participants |
p-value: 0.6616Binomial test
Secondary
Overall Response Rate in Patients With Central Nervous System Involvement at Baseline
Overall response rate is defined as the proportion of patients who have a partial or complete response in the best antitumor response. The best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1. CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown
Time frame: Every three months up to death or study termination, a period of approximately 3.5 years
Population: A preplanned exploratory efficacy subgroup analysis was focused on patients with Central Nervous System Involvement at Baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lurbinectedin/Doxorubicin | Overall Response Rate in Patients With Central Nervous System Involvement at Baseline | 23.9 percentage of participants |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Overall Response Rate in Patients With Central Nervous System Involvement at Baseline | 24.5 percentage of participants |
95% CI: [0.403, 2.641]
Secondary
Overall Response Rate in Patients With Chemotherapy-free Interval <90 Days
Overall response rate is defined as the proportion of patients who have a partial or complete response in the best antitumor response. The best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1. CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown
Time frame: Every three months up to death or study termination, a period of approximately 3.5 years
Population: A preplanned exploratory efficacy subgroup analysis was focused on patients had chemotherapy-free interval \<90 days after first-line chemotherapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lurbinectedin/Doxorubicin | Overall Response Rate in Patients With Chemotherapy-free Interval <90 Days | 20.2 percentage of participants |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Overall Response Rate in Patients With Chemotherapy-free Interval <90 Days | 18.8 percentage of participants |
95% CI: [0.455, 1.843]
Secondary
Overall Response Rate in Patients With Chemotherapy-free Interval ≥ 90 Days
Overall response rate is defined as the proportion of patients who have a partial or complete response in the best antitumor response. The best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1. CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown
Time frame: Every three months up to death or study termination, a period of approximately 3.5 years
Population: A preplanned exploratory efficacy subgroup analysis was focused on patients had chemotherapy-free interval ≥90 days after first-line chemotherapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lurbinectedin/Doxorubicin | Overall Response Rate in Patients With Chemotherapy-free Interval ≥ 90 Days | 37.0 percentage of participants |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Overall Response Rate in Patients With Chemotherapy-free Interval ≥ 90 Days | 35.1 percentage of participants |
95% CI: [0.616, 1.376]
Secondary
Overall Response Rate in Patients Without Central Nervous System Involvement at Baseline
Overall response rate is defined as the proportion of patients who have a partial or complete response in the best antitumor response. The best antitumor response will be the best response obtained in any evaluation according to RECIST v.1.1. CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; UK,unknown
Time frame: Every three months up to death or study termination, a period of approximately 3.5 years
Population: A preplanned exploratory efficacy subgroup analysis was focused on patients without Central Nervous System Involvement at Baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lurbinectedin/Doxorubicin | Overall Response Rate in Patients Without Central Nervous System Involvement at Baseline | 33.0 percentage of participants |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Overall Response Rate in Patients Without Central Nervous System Involvement at Baseline | 30.7 percentage of participants |
95% CI: [0.624, 1.307]
Secondary
Overall Survival in Patients With Central Nervous System Involvement at Baseline
Overall survival (OS) will be calculated from the date of randomization to the date of death (death event) or last contact(in this case, survival will be censored on that date).
Time frame: Every three months up to death or study termination, a period of approximately 3.5 years
Population: A preplanned exploratory efficacy subgroup analysis was focused on patients with Central Nervous System Involvement at Baseline
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lurbinectedin/Doxorubicin | Overall Survival in Patients With Central Nervous System Involvement at Baseline | 4.6 months |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Overall Survival in Patients With Central Nervous System Involvement at Baseline | 6.6 months |
95% CI: [0.838, 1.99]
Secondary
Overall Survival in Patients With Chemotherapy-free Interval < 90 Days
Overall survival (OS) will be calculated from the date of randomization to the date of death (death event) or last contact(in this case, survival will be censored on that date).
Time frame: Every three months up to death or study termination, a period of approximately 3.5 years
Population: A preplanned exploratory efficacy subgroup analysis was focused on patients had chemotherapy-free interval \<90 days after first-line chemotherapy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lurbinectedin/Doxorubicin | Overall Survival in Patients With Chemotherapy-free Interval < 90 Days | 5.7 months |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Overall Survival in Patients With Chemotherapy-free Interval < 90 Days | 5.3 months |
95% CI: [0.84, 1.5]
Secondary
Overall Survival in Patients With Chemotherapy-free Interval ≥ 90 Days
Overall survival (OS) will be calculated from the date of randomization to the date of death (death event) or last contact(in this case, survival will be censored on that date).
Time frame: Every three months up to death or study termination, a period of approximately 3.5 years
Population: A preplanned exploratory efficacy subgroup analysis was focused on patients had chemotherapy-free interval ≥90 days after first-line chemotherapy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lurbinectedin/Doxorubicin | Overall Survival in Patients With Chemotherapy-free Interval ≥ 90 Days | 10.3 months |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Overall Survival in Patients With Chemotherapy-free Interval ≥ 90 Days | 8.7 months |
95% CI: [0.744, 1.14]
Secondary
Overall Survival in Patients Without Central Nervous System Involvement at Baseline
Overall survival (OS) will be calculated from the date of randomization to the date of death (death event) or last contact(in this case, survival will be censored on that date).
Time frame: Every three months up to death or study termination, a period of approximately 3.5 years
Population: A preplanned exploratory efficacy subgroup analysis was focused on patients without Central Nervous System Involvement at Baseline
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lurbinectedin/Doxorubicin | Overall Survival in Patients Without Central Nervous System Involvement at Baseline | 9.1 months |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Overall Survival in Patients Without Central Nervous System Involvement at Baseline | 7.7 months |
95% CI: [0.765, 1.113]
Secondary
Progression-free Survival in Patients With Central Nervous System Involvement at Baseline
Progression-free survival (PFS) is 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 receives further antitumor therapy or is lost to follow-up before PD, PFS will be censored at the date of last tumor assessment before the date of subsequent antitumor therapy.
Time frame: Every six weeks up to progression disease, a period of approximately 3.5 years
Population: A preplanned exploratory efficacy subgroup analysis was focused on patients with Central Nervous System Involvement at Baseline
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lurbinectedin/Doxorubicin | Progression-free Survival in Patients With Central Nervous System Involvement at Baseline | 1.9 months |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Progression-free Survival in Patients With Central Nervous System Involvement at Baseline | 2.8 months |
95% CI: [0.824, 2.019]
Secondary
Progression-free Survival in Patients With Chemotherapy-free Interval <90 Days
Progression-free survival (PFS) is 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 receives further antitumor therapy or is lost to follow-up before PD, PFS will be censored at the date of last tumor assessment before the date of subsequent antitumor therapy.
Time frame: Every six weeks up to progression disease, a period of approximately 3.5 years
Population: A preplanned exploratory efficacy subgroup analysis was focused on patients had chemotherapy-free interval \<90 days after first-line chemotherapy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lurbinectedin/Doxorubicin | Progression-free Survival in Patients With Chemotherapy-free Interval <90 Days | 1.6 months |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Progression-free Survival in Patients With Chemotherapy-free Interval <90 Days | 2.8 months |
95% CI: [0.955, 1.786]
Secondary
Progression-free Survival in Patients With Chemotherapy-free Interval ≥90 Days
Progression-free survival (PFS) is 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 receives further antitumor therapy or is lost to follow-up before PD, PFS will be censored at the date of last tumor assessment before the date of subsequent antitumor therapy.
Time frame: Every six weeks up to progression disease, a period of approximately 3.5 years
Population: A preplanned exploratory efficacy subgroup analysis was focused on patients had chemotherapy-free interval ≥90 days after first-line chemotherapy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lurbinectedin/Doxorubicin | Progression-free Survival in Patients With Chemotherapy-free Interval ≥90 Days | 4.8 months |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Progression-free Survival in Patients With Chemotherapy-free Interval ≥90 Days | 4.4 months |
95% CI: [0.549, 0.863]
Secondary
Progression-free Survival in Patients Without Central Nervous System Involvement at Baseline
Progression-free survival (PFS) is 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 receives further antitumor therapy or is lost to follow-up before PD, PFS will be censored at the date of last tumor assessment before the date of subsequent antitumor therapy.
Time frame: Every six weeks up to progression disease, a period of approximately 3.5 years
Population: A preplanned exploratory efficacy subgroup analysis was focused on patients without Central Nervous System Involvement at Baseline
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lurbinectedin/Doxorubicin | Progression-free Survival in Patients Without Central Nervous System Involvement at Baseline | 4.2 months |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Progression-free Survival in Patients Without Central Nervous System Involvement at Baseline | 4.1 months |
95% CI: [0.645, 0.961]
Secondary
Progression-free Survival (PFS) by Independent Review Committee
Progression-free survival (PFS) is 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 receives further antitumor therapy or is lost to follow-up before PD, PFS will be censored at the date of last tumor assessment before the date of subsequent antitumor therapy.
Time frame: Every six weeks up to progression disease, a period of approximately 3.5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lurbinectedin/Doxorubicin | Progression-free Survival (PFS) by Independent Review Committee | 4.0 months |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Progression-free Survival (PFS) by Independent Review Committee | 4.0 months |
p-value: 0.325795% CI: [0.693, 0.996]Log Rank
Secondary
Progression-free Survival Rate at 12 Months by Independent Review Committee
Progression-free survival (PFS) is 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 receives further antitumor therapy or is lost to follow-up before PD, PFS will be censored at the date of last tumor assessment before the date of subsequent antitumor therapy.
Time frame: at 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lurbinectedin/Doxorubicin | Progression-free Survival Rate at 12 Months by Independent Review Committee | 10.8 percentage of participants |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Progression-free Survival Rate at 12 Months by Independent Review Committee | 4.4 percentage of participants |
p-value: 0.0129Normal test
Secondary
Progression-free Survival Rate at 6 Months by Independent Review Committee
Progression-free survival (PFS) is 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 receives further antitumor therapy or is lost to follow-up before PD, PFS will be censored at the date of last tumor assessment before the date of subsequent antitumor therapy.
Time frame: At 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lurbinectedin/Doxorubicin | Progression-free Survival Rate at 6 Months by Independent Review Committee | 31.3 percentage of participants |
| Topotecan or Cyclophosphamide/Doxorubicin/Vincristine | Progression-free Survival Rate at 6 Months by Independent Review Committee | 24.4 percentage of participants |
p-value: 0.0851Normal test