El Abstract de ESMO 24 :
1790P - Phase II data of lurbinectedin (LUR) and irinotecan (IRI) in relapsed small cell lung cancer (SCLC) patients (pts) with chemotherapy-free interval (CTFI)>30 days (d)
- Jon Zugazagoitia (Madrid, Spain)
- Jon Zugazagoitia (Madrid, Spain)
- Alejandro Falcon Gonzalez (Seville, Spain)
- Alejandro F. Navarro Mendivil (Barcelona, Spain)
- Amparo Sanchez Gastaldo (Seville, Spain)
- Pedro F. Simoes da Rocha (Barcelona, Spain)
- Gregory M. Cote (Boston, United States of America)
- Bruno Bockorny (Boston, United States of America)
- Javier Molina Cerrillo (Madrid, Spain)
- Angel Artal (Zaragoza, Spain)
- Javier Baena Espinar (Madrid, Spain)
- Ana Gil Torralvo (Seville, Spain)
- Santiago Ponce Aix (Villejuif, Cedex, France)
- Helena Bote De Cabo (Madrid, Spain)
- Julia Martinez Perez (Seville, Spain)
- Sara Martínez (Colmenar Viejo, Spain, Madrid)
- Jose Antonio López-Vilariño (Colmenar Viejo, Spain)
- Carmen Kahatt (Colmenar Viejo, Spain)
- Javier Gómez (Colmenar Viejo, Spain)
- Luis G. Paz-Ares (Madrid, Spain)
Background
LUR has been approved in the US and other countries for treating adult pts with metastatic SCLC and disease progression on or after platinum (Pt)-based chemotherapy. LUR with IRI showed synergy in preclinical studies. A phase Ib/II trial (NCT02611024) found promising activity and a manageable safety profile in 101 pts with relapsed SCLC treated at the RD of LUR 2.0 mg/m2 on Day (D)1 + IRI 75 mg/m2 on D1, D8 every three weeks with primary G-CSF prophylaxis. An analysis of a subpopulation of SCLC pts with CTFI>30 d is presented here.
Methods
Eligibility criteria: confirmed SCLC, progression after one Pt-based line, CTFI>30 d, controlled brain metastases and ECOG PS ≤ 1.
Results
74 of the 101 evaluable SCLC pts had CTFI>30 d. Baseline characteristics: median age 64 y (range, 45-77 y), 60.8% males, 73.0% ECOG PS 1, 31.1% CNS involvement, 31.1% bulky disease and 40.5% pretreated with immunotherapy. 33.8% had CTFI <90 d. Median CTFI 108.5 d (range, 37-323 d). Median no. of cycles per pt was 7 (range, 1-34); 27.0% received >10 cycles. Efficacy results assessed by independent review committee are shown below:
| All pts with CTFI>30 d (n=74) | CTFI 30-90 d (n=25) | CTFI≥90 d (n=49) | |
| 51.4 (39.4-63.1) | 32.0 (14.9-53.5) | 61.2 (46.2-74.8) | |
| 8.2 (5.4-11.7) | 7.6 (3.7-9.7) | 8.4 (4.6-12.7) | |
| 5.6 (4.1-7.2) | 4.3 (3.0-7.0) | 6.2 (4.2-9.6) | |
| 12.7 (9.1-14.1) | 8.8 (3.7-13.6) | 14.0 (10.1-16.1) | |
| 52.5 (40.1-64.9) | 34.1 (13.8-54.5) | 61.7 (46.6-76.7) |
CI, confidence interval; CTFI, chemotherapy-free interval; d, days; DoR, duration of response; mo, months; ORR, overall response rate; OS, overall survival; PFS, progression free survival.
Treatment-related adverse events (AEs) occurred in 98.6% of pts. 71.6% had grade ≥3 events; most relevant were neutropenia (59.5%), anaemia (28.4%), diarrhoea (18.9%), fatigue (16.2%), and febrile neutropenia (13.5%). 31.1% of pts had treatment-related serious AEs, and 6.8% discontinued due to treatment-related AEs. No treatment-related deaths occurred.
Conclusions
The LUR+IRI combination had a highly promising activity and an acceptable safety profile in pts with relapsed SCLC after one Pt-based line. Efficacy was evident not only in sensitive disease (CTFI>90 d) but also in pts with CTFI 30-90 d, who typically have a poor prognosis. These findings bolster the rationale for including this combination in the currently recruiting LAGOON trial (NCT05153239) in relapsed SCLC pts with CTFI>30 d.
Clinical trial identification
NCT05153239.
Legal entity responsible for the study
PharmaMar.
Resumen :
PHASE II Efficacy And Safety Of LURBINECTEDIN With IRINOTECAN in Patients With RELAPSED SMALL CELL LUNG CÁNCER ( SEGUNDA LÍNEA ) . PFS : 5,6 MESES . OS : 12,7 MESES . Treatment-Related Adverse Events (AEs) Were Observed in 99.0% of Patients ( Grade ≥3 in 69.3% ) .
No Hay Presentación Oral ...
Y Nada se Presentó Sobre las Fases III LAGOON NI IMFORTE .
The PHASE 1b/2 study PM1183-A-014-15 (NCT02611024) evaluated the LUR/IRI combination in pretreated pts with advanced solid tumors . The phase 1b part defined the recommended dose at LUR 2.0 mg/m2 on Day (D)1 + IRI 75 mg/m2 on D1,D8 every three weeks with primary G-CSF prophylaxis, and found promising results for the combination in SCLC pts after first-line therapy (Ponce Aix S. Ann Oncol 2019; 30: Abst 471P) .Methods :Eligibility criteria for this cohort of the Phase 2 part of this study included : Confirmed SCLC, progression after one platinum-containing regimen, controlled brain metastases and ECOG PS ≤ 1. The primary endpoint was overall response rate (ORR).Results :74 of the 101 evaluable SCLC pts had CTFI>30 d. Baseline characteristics: median age 64 y (range, 45-77 y), 60.8% males, 73.0% ECOG PS 1, 31.1% CNS involvement, 31.1% bulky disease and 40.5% pretreated with immunotherapy. 33.8% had CTFI <90 d. Median CTFI 108.5 d (range, 37-323 d). Median no. of cycles per pt was 7 (range, 1-34); 27.0% received >10 cycles. Efficacy results assessed by independent review committee are shown below .
Treatment-related adverse events (AEs) occurred in 98.6% of pts. 71.6% had grade ≥3 events; most relevant were neutropenia (59.5%), anaemia (28.4%), diarrhoea (18.9%), fatigue (16.2%), and febrile neutropenia (13.5%). 31.1% of pts had treatment-related serious AEs, and 6.8% discontinued due to treatment-related AEs. No treatment-related deaths occurred .
Conclusions :
The LUR+IRI combination had a highly promising activity and an acceptable safety profile in pts with relapsed SCLC after one Pt-based line . Efficacy was evident not only in sensitive disease (CTFI>90 d) but also in pts with CTFI 30-90 d, who typically have a poor prognosis . These findings bolster the rationale for including this combination in the currently recruiting LAGOON trial (NCT05153239) in relapsed SCLC pts with CTFI>30 d.