Non-Small Cell Lung Cancer (NSCLC)
Conditions
Brief summary
A clinical study of lurbinectedin(PM01183) alone or in combination with gemcitabine in comparison to docetaxel for the treatment of unresectable non-small cell lung cancer (NSCLC)patients
Detailed description
A randomized-controlled, three-arm, phase II study of lurbinectedin (PM01183) alone or in combination with gemcitabine and a control arm with docetaxel as second-line treatment in unresectable non-small cell lung cancer (NSCLC)patients to evaluate the antitumor activity as progression-free survival at four months (PFS4) of PM01183 alone or in combination with gemcitabine as using single agent docetaxel as a reference in the control arm as current standard of care and to analyze overall survival (OS), overall survival rate at 1-year (OS12), duration of response (DR), antitumor activity, as response rate (RR), safety and efficacy profiles of PM01183 alone and in combination with gemcitabine, to be preliminary compared with docetaxel, patients' quality of life (QoL), pharmacokinetics (PK) of PM01183, pharmacokinetic/pharmacodynamic (PK/PD)correlation and pharmacogenomics (PGx)to explore potential correlations between clinical outcomes and molecular parameters found in tumor and blood samples
Interventions
DRUGDocetaxel
Powder for solution for infusion
DRUGGemcitabine
Powder for solution for infusion
Powder for concentrate for solution for infusion
Sponsors
PharmaMar
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed unresectable NSCLC * Patients must have failed one prior line of CT-based therapy for unresectable disease * Age between 18 and 75 years * Eastern Cooperative Oncology Group (ECOG)performance status (PS) ≤ 1 * Adequate hematological, renal, metabolic and hepatic function * At least three weeks since the last prior therapy, at least four weeks since completion of any prior radiotherapy * Negative pregnancy test for pre-menopausal women
Exclusion criteria
* Concomitant diseases/conditions as unstable angina, myocardial infarction, symptomatic congestive heart failure or asymptomatic with left ventricular ejection fraction (LVEF) ≤ 50%, dyspnea, infection by human immunodeficiency virus (HIV), active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, active uncontrolled infection, pleural or pericardial effusions, myopathy, limitation of the patient's ability to comply with the treatment or to follow-up the protocol, any other major illness * Histological features of neuroendocrine or bronchioalveolar differentiation. * Unknown epidermal growth factor receptor (EGFR)mutation status or previously known EGFR mutated status in patients with adenocarcinoma. * Prior or concurrent invasive malignant disease, unless in complete remission for more than three years. * Significant cancer-related weight loss (≥10%)within four weeks prior to treatment start * Prior treatment with docetaxel-containing therapy * Symptomatic, steroid-requiring or progressive central nervous system (CNS) involvement * Paraneoplastic syndromes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival Rate at Four Months (PFS4) | At month four after patient inclusion | The rate estimate of the percentage of patients who are alive and progression-free at 16 weeks (\ 4 months) after randomization. Progession disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival Rate at Six Months (PFS6) | At month six after patient inclusion | The rate estimate of the percentage of patients who are alive and progression-free at 24 weeks (\ 6 months) after randomization. Progession disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. |
| Overall Response Rate | Time from the date of randomization until 30±7 days after the last treatment infusion, assessed up to 3 years | Overall response rate (ORR) was defined as the percentage of patients with a response, either CR or PR, according to RECIST v.1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| Objective Response Per RECIST v.1.1 | Time from the date of randomization until 30±7 days after the last treatment infusion, assessed up to 3 years | RECIST, Response Evaluation Criteria In Solid Tumors Complete Response (CR) Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10mm Partial Response (PR) At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters Progressive Disease (PD) At least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. Appearance of new lesions was considered PD Stable Disease (SD) Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum diameters while on study Treatment failure (TF) Symptomatic deterioration/death due to progression or treatment discontinuation due to treatment-related toxicity occurred before any appropriate tumor assessments had been performed |
| Progression-free Survival | 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 | PFS, progression-free survival Progression-free survival (PFS), defined as the time from the date of randomization to the date of PD, death (of any cause), or last tumor evaluation. Progession disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. |
| Overall Survival (OS) | From the date of first infusion to the date of death or last contact, up to 12 months after last patient inclusion | Overall survival (OS) will be defined as time from the date of first infusion to the date of death or last contact |
| Information on Quality of Life (QoL) | Baseline, Cycle 3 (~9 weeks), Cycle 6 (~18 weeks) and Cycle 9 (~27 weeks) | The mean QoL scores self-reported by patients using the Lung Cancer Symptom Scale (LCSS) at baseline and after the start of the therapy in visits 3 or 6 (+/- 1 visit) and visit 9 for those patients in maintenance therapy. Higher LCSS scores indicate more severe problems and the scale range is (0-100) Total score was calculated as the mean of the total scores of all nine patient ítems (Appetite, Fatigue, Cough, Dyspnea, Hemoptysis, Pain, Lung cancer symptoms, Normal activities, Global QoL) |
| Duration of Response | 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 | Duration of response (DR) was defined as 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. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
Countries
United States
Participant flow
Recruitment details
69 patients were enrolled between 11/09/2013 and 2/10/2015 at 13 centers. 68 patients were treated: 22 in Arm A, 21 in Arm B, and 25 in Arm C. The first dose of the first cycle was administered on 17/09/2013 and the last dose of the last cycle was administered on 3/11/2016. The last patient, last follow-up was on 24/11/2016
Participants by arm
| Arm | Count |
|---|---|
| A - Docetaxel 75 mg/m2 docetaxel day 1, 1-hour intravenous, every three weeks
Docetaxel: Powder for solution for infusion | 22 |
| B - Lurbinectedin (PM01183) In the first protocol version, PM01183 7 mg Flat dose, 1-h i.v. infusion (at a fixed rate), on D1, q3wk, up to 6 cycles After protocol amendment 3, PM01183 3.2 mg/m2, 1-h i.v. infusion (at a fixed rate), on D1, q3wk, up to 6 cycles
Lurbinectedin (PM01183): Powder for concentrate for solution for infusion | 22 |
| C - Gemcitabine + Lurbinectedin (PM01183) Gemcitabine 800 mg/m2, 30-min i.v. infusion, immediately followed by PM01183 3.0 mg Flat dose, 1-h i.v. infusion (at a fixed rate), on D1, q3wk, up to 6 cycles (in the first protocol version) or PM01183 1.6 mg/m2, 1-h i.v. infusion (at a fixed rate), on D1, q3wk, up to 6 cycles (after protocol amendment 3)
Gemcitabine: Powder for solution for infusion
Lurbinectedin (PM01183): Powder for concentrate for solution for infusion | 25 |
| Total | 69 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Consent withdrawn by subject | 0 | 1 | 3 |
| Overall Study | Non-treatmentrelated death | 2 | 2 | 2 |
| Overall Study | No treated | 0 | 1 | 0 |
| Overall Study | Physician Decision | 5 | 3 | 2 |
| Overall Study | Progressive Disease | 12 | 13 | 10 |
| Overall Study | Study Termination | 0 | 0 | 1 |
| Overall Study | Treatment-related AE | 2 | 0 | 4 |
| Overall Study | Treatment-related death | 0 | 2 | 0 |
| Overall Study | Treatment-unrelated AE | 1 | 0 | 3 |
Baseline characteristics
| Characteristic | Total | C - Gemcitabine + Lurbinectedin (PM01183) | A - Docetaxel | B - Lurbinectedin (PM01183) |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 31 Participants | 12 Participants | 7 Participants | 12 Participants |
| Age, Categorical Between 18 and 65 years | 38 Participants | 13 Participants | 15 Participants | 10 Participants |
| Age, Continuous | 63 years | 64 years | 61.5 years | 65 years |
| Albumin | 4 g/dL | 4 g/dL | 4.3 g/dL | 3.9 g/dL |
| Alpha-1-acid glycoprotein | 161 mg/dL | 159 mg/dL | 172 mg/dL | 141 mg/dL |
| Best response to last prior platinum NA | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Best response to last prior platinum PD | 13 Participants | 5 Participants | 5 Participants | 3 Participants |
| Best response to last prior platinum PR | 31 Participants | 9 Participants | 11 Participants | 11 Participants |
| Best response to last prior platinum SD | 23 Participants | 10 Participants | 5 Participants | 8 Participants |
| Best response to last prior platinum UK | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Body Surface Area | 1.8 m^2 | 1.9 m^2 | 1.8 m^2 | 1.9 m^2 |
| ECOG PS PS 0 | 27 Participants | 10 Participants | 6 Participants | 11 Participants |
| ECOG PS PS 1 | 42 Participants | 15 Participants | 16 Participants | 11 Participants |
| Histology grade Moderately differentiated | 8 Participants | 1 Participants | 2 Participants | 5 Participants |
| Histology grade Poorly differentiated | 19 Participants | 9 Participants | 7 Participants | 3 Participants |
| Histology grade Unknown | 41 Participants | 15 Participants | 13 Participants | 13 Participants |
| Histology grade Well differentiated | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Histology type Non-squamous-cell | 54 Participants | 19 Participants | 17 Participants | 18 Participants |
| Histology type Not specified | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Histology type Squamous-cell | 14 Participants | 6 Participants | 4 Participants | 4 Participants |
| Number of sites involved at baseline | 3 sites | 3 sites | 3 sites | 3 sites |
| PFS to last prior line | 5.8 mohths | 5.4 mohths | 5.7 mohths | 6.7 mohths |
| Platinum-free interval | 4.4 months | 3.9 months | 3.5 months | 5.6 months |
| Prior chemotherapy 1 line | 63 Participants | 23 Participants | 19 Participants | 21 Participants |
| Prior chemotherapy 2 lines | 6 Participants | 2 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Caucasian | 68 Participants | 25 Participants | 21 Participants | 22 Participants |
| Race/Ethnicity, Customized Race Unknown | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Radiotherapy No | 40 Participants | 15 Participants | 13 Participants | 12 Participants |
| Radiotherapy Yes | 29 Participants | 10 Participants | 9 Participants | 10 Participants |
| Region of Enrollment Belgium | 3 Participants | 0 Participants | 0 Participants | 3 Participants |
| Region of Enrollment Italy | 32 Participants | 13 Participants | 8 Participants | 11 Participants |
| Region of Enrollment Spain | 32 Participants | 12 Participants | 12 Participants | 8 Participants |
| Region of Enrollment United States | 2 Participants | 0 Participants | 2 Participants | 0 Participants |
| Sex: Female, Male Female | 19 Participants | 9 Participants | 5 Participants | 5 Participants |
| Sex: Female, Male Male | 50 Participants | 16 Participants | 17 Participants | 17 Participants |
| Signs and symptoms per patient | 1 Signs and symptoms | 1 Signs and symptoms | 1 Signs and symptoms | 1 Signs and symptoms |
| Stage at diagnosis Early | 4 Participants | 2 Participants | 1 Participants | 1 Participants |
| Stage at diagnosis Locally advanced | 15 Participants | 4 Participants | 4 Participants | 7 Participants |
| Stage at diagnosis Metastatic | 47 Participants | 18 Participants | 15 Participants | 14 Participants |
| Stage at diagnosis Unknown | 3 Participants | 1 Participants | 2 Participants | 0 Participants |
| Stage at study entry Locally advanced | 3 Participants | 2 Participants | 1 Participants | 0 Participants |
| Stage at study entry Metastatic | 66 Participants | 23 Participants | 21 Participants | 22 Participants |
| Surgery No | 58 Participants | 22 Participants | 19 Participants | 17 Participants |
| Surgery Yes | 11 Participants | 3 Participants | 3 Participants | 5 Participants |
| Time from first diagnosis to first infusion | 9.8 months | 9.2 months | 8 months | 11.4 months |
| Weight | 73.6 Kg | 77 Kg | 70.5 Kg | 74 Kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 14 / 22 | 17 / 21 | 21 / 25 |
| other Total, other adverse events | 21 / 22 | 20 / 21 | 25 / 25 |
| serious Total, serious adverse events | 12 / 22 | 9 / 21 | 18 / 25 |
Outcome results
Primary
Progression-free Survival Rate at Four Months (PFS4)
The rate estimate of the percentage of patients who are alive and progression-free at 16 weeks (\ 4 months) after randomization. Progession disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression.
Time frame: At month four after patient inclusion
Population: Arm B: 1 no treated, 1 no tumour assesment, 1 major protocol deviation Arm C: 2 no tumour assesment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A - Docetaxel | Progression-free Survival Rate at Four Months (PFS4) | 27.3 percentage of participants |
| B - Lurbinectedin (PM01183) | Progression-free Survival Rate at Four Months (PFS4) | 15.8 percentage of participants |
| C - Gemcitabine + Lurbinectedin (PM01183) | Progression-free Survival Rate at Four Months (PFS4) | 26.1 percentage of participants |
Comparison: The exact binomial estimator and its 95%CI was used. A pre-planned Bayesian supportive analysis test comparing PFS4 was performed.95% CI: [13.2, 48.4]
Comparison: The exact binomial estimator and its 95%CI was used. A pre-planned Bayesian supportive analysis test comparing PFS4 was performed95% CI: [5.7, 37.9]
Comparison: The exact binomial estimator and its 95%CI was used. A pre-planned Bayesian supportive analysis test comparing PFS4 was performed95% CI: [12.6, 46.7]
Secondary
Duration of Response
Duration of response (DR) was defined as 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. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: 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: Two patients with CR or PR to treatment as per the RECIST v.1.1 criteria were found in Arm A.~No patients with CR or PR to treatment as per the RECIST v.1.1 criteria were found in Arm B.~Four patients with CR or PR to treatment as per the RECIST v.1.1 criteria were found in Arm C.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| A - Docetaxel | Duration of Response | 1.2 months |
| C - Gemcitabine + Lurbinectedin (PM01183) | Duration of Response | 6.1 months |
p-value: =0.0177Log Rank
Secondary
Information on Quality of Life (QoL)
The mean QoL scores self-reported by patients using the Lung Cancer Symptom Scale (LCSS) at baseline and after the start of the therapy in visits 3 or 6 (+/- 1 visit) and visit 9 for those patients in maintenance therapy. Higher LCSS scores indicate more severe problems and the scale range is (0-100) Total score was calculated as the mean of the total scores of all nine patient ítems (Appetite, Fatigue, Cough, Dyspnea, Hemoptysis, Pain, Lung cancer symptoms, Normal activities, Global QoL)
Time frame: Baseline, Cycle 3 (~9 weeks), Cycle 6 (~18 weeks) and Cycle 9 (~27 weeks)
Population: No patients in cycle 9 in arm A and arm C.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| A - Docetaxel | Information on Quality of Life (QoL) | Cycle 3 | 29.5 units on a scale |
| A - Docetaxel | Information on Quality of Life (QoL) | Baseline | 27.2 units on a scale |
| A - Docetaxel | Information on Quality of Life (QoL) | Cycle 6 | 24.3 units on a scale |
| B - Lurbinectedin (PM01183) | Information on Quality of Life (QoL) | Cycle 9 | 38.1 units on a scale |
| B - Lurbinectedin (PM01183) | Information on Quality of Life (QoL) | Baseline | 36.4 units on a scale |
| B - Lurbinectedin (PM01183) | Information on Quality of Life (QoL) | Cycle 3 | 32.2 units on a scale |
| B - Lurbinectedin (PM01183) | Information on Quality of Life (QoL) | Cycle 6 | 55.4 units on a scale |
| C - Gemcitabine + Lurbinectedin (PM01183) | Information on Quality of Life (QoL) | Baseline | 38.1 units on a scale |
| C - Gemcitabine + Lurbinectedin (PM01183) | Information on Quality of Life (QoL) | Cycle 6 | 35.4 units on a scale |
| C - Gemcitabine + Lurbinectedin (PM01183) | Information on Quality of Life (QoL) | Cycle 3 | 36.4 units on a scale |
Comparison: Changes in QoL scores over time were calculated and tested for statistical significance by means of wilcoxon signed ranks test repeat-measure analyses of variance.p-value: 0.9026Wilcoxon signed ranks test repeat analys
Comparison: Changes in QoL scores over time were calculated and tested for statistical significance by means of wilcoxon signed ranks test repeat-measure analyses of variance.p-value: 0.9862Wilcoxon signed ranks test repeat analys
Comparison: Changes in QoL scores over time were calculated and tested for statistical significance by means of ilcoxon signed ranks test repeat-measure analyses of variance.p-value: 0.8057Wilcoxon signed ranks test repeat analys
Secondary
Objective Response Per RECIST v.1.1
RECIST, Response Evaluation Criteria In Solid Tumors Complete Response (CR) Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10mm Partial Response (PR) At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters Progressive Disease (PD) At least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. Appearance of new lesions was considered PD Stable Disease (SD) Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum diameters while on study Treatment failure (TF) Symptomatic deterioration/death due to progression or treatment discontinuation due to treatment-related toxicity occurred before any appropriate tumor assessments had been performed
Time frame: Time from the date of randomization until 30±7 days after the last treatment infusion, assessed up to 3 years
Population: B- 1 no treated, 1 no tumour assesment, 1 major protocol deviation C- 2 no tumour assesment
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| A - Docetaxel | Objective Response Per RECIST v.1.1 | TF | 2 Participants |
| A - Docetaxel | Objective Response Per RECIST v.1.1 | PR | 2 Participants |
| A - Docetaxel | Objective Response Per RECIST v.1.1 | PD | 8 Participants |
| A - Docetaxel | Objective Response Per RECIST v.1.1 | SD | 10 Participants |
| B - Lurbinectedin (PM01183) | Objective Response Per RECIST v.1.1 | PD | 8 Participants |
| B - Lurbinectedin (PM01183) | Objective Response Per RECIST v.1.1 | TF | 4 Participants |
| B - Lurbinectedin (PM01183) | Objective Response Per RECIST v.1.1 | SD | 7 Participants |
| B - Lurbinectedin (PM01183) | Objective Response Per RECIST v.1.1 | PR | 0 Participants |
| C - Gemcitabine + Lurbinectedin (PM01183) | Objective Response Per RECIST v.1.1 | TF | 2 Participants |
| C - Gemcitabine + Lurbinectedin (PM01183) | Objective Response Per RECIST v.1.1 | SD | 11 Participants |
| C - Gemcitabine + Lurbinectedin (PM01183) | Objective Response Per RECIST v.1.1 | PD | 6 Participants |
| C - Gemcitabine + Lurbinectedin (PM01183) | Objective Response Per RECIST v.1.1 | PR | 4 Participants |
Secondary
Overall Response Rate
Overall response rate (ORR) was defined as the percentage of patients with a response, either CR or PR, according to RECIST v.1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: Time from the date of randomization until 30±7 days after the last treatment infusion, assessed up to 3 years
Population: B - 1 no treated, 1 no tumour assesment, 1 major protocol deviation C - 2 no tumour assesment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A - Docetaxel | Overall Response Rate | 9.1 percentage of participants |
| B - Lurbinectedin (PM01183) | Overall Response Rate | 0 percentage of participants |
| C - Gemcitabine + Lurbinectedin (PM01183) | Overall Response Rate | 17.4 percentage of participants |
Secondary
Overall Survival (OS)
Overall survival (OS) will be defined as time from the date of first infusion to the date of death or last contact
Time frame: From the date of first infusion to the date of death or last contact, up to 12 months after last patient inclusion
Population: Arm B: 1 no treated, 1 no tumour assesment, 1 major protocol deviation Arm C: 2 no tumour assesment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| A - Docetaxel | Overall Survival (OS) | 9.4 months |
| B - Lurbinectedin (PM01183) | Overall Survival (OS) | 5.5 months |
| C - Gemcitabine + Lurbinectedin (PM01183) | Overall Survival (OS) | 7.2 months |
p-value: 0.3526Log Rank
Secondary
Progression-free Survival
PFS, progression-free survival Progression-free survival (PFS), defined as the time from the date of randomization to the date of PD, death (of any cause), or last tumor evaluation. Progession disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression.
Time frame: 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
Population: B- 1 no treated, 1 no tumour assesment, 1 major protocol deviation C - 2 no tumour assesment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| A - Docetaxel | Progression-free Survival | 3.1 months |
| B - Lurbinectedin (PM01183) | Progression-free Survival | 1.9 months |
| C - Gemcitabine + Lurbinectedin (PM01183) | Progression-free Survival | 3.3 months |
p-value: =0.3873Log Rank
Secondary
Progression-free Survival Rate at Six Months (PFS6)
The rate estimate of the percentage of patients who are alive and progression-free at 24 weeks (\ 6 months) after randomization. Progession disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression.
Time frame: At month six after patient inclusion
Population: B- 1 no treated, 1 no tumour assesment, 1 major protocol deviation C - 2 no tumour assesment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A - Docetaxel | Progression-free Survival Rate at Six Months (PFS6) | 18.2 percentage of participants |
| B - Lurbinectedin (PM01183) | Progression-free Survival Rate at Six Months (PFS6) | 16.7 percentage of participants |
| C - Gemcitabine + Lurbinectedin (PM01183) | Progression-free Survival Rate at Six Months (PFS6) | 17.5 percentage of participants |