REACTION: A phase II study of etoposide and cis/carboplatin with or without pembrolizumab in untreated extensive small cell lung cancer
De Marinis, F.
Banna, G. L.
Dingemans, A. M. C.
AffiliationDept. of Cancer Medicine, Institut Gustave Roussy, Villejuif, France
MetadataShow full item record
AbstractBackground: Anti-PD-L1 antibodies extend overall survival (OS) of patients with extensive disease Small Cell Lung Cancer (ED-SCLC) when combined with platinumetoposide (Pl-E) from cycle 1. We evaluated the benefit of first-line pembrolizumab (P) combined with Pl-E from cycle 3 in the subgroup of chemo-sensitive ED-SCLC. Methods: REACTION is a multicenter, open-label, randomized phase II trial. Patients with ED-SCLC, unselected for PD-L1, with PS 0/1 and controlled brain metastases who achieved an objective response after 2 X Pl-E were randomized 1:1 to experimental arm (EXP) P in combination with 4 X Pl-E then P up to 35 cycles vs. 4 X Pl-E in the control (CTRL) arm. Cross-over to P-Pl-E was allowed for CTRL. Primary endpoint was progression free survival (PFS) from randomization. With a 1-sided alpha 10%, the study was powered at 90% level to detect a Hazard Ratio (HR) of 0.575 in PFS. Results: Between Feb 7, 2018 and Oct 31, 2019, 125 patients were recruited (61 in EXP arm vs 64 in CTRL arm) with 119 (58 vs 61) eligible and receiving at least one dose of treatment (Per Protocol [PP] population). Median age was 65 vs 63.5 years with the majority being male (72 vs 56%), PS 1 (62 vs 60%), and rare brain metastases (8 vs 11%). Most patients had partial response (PR) to the induction chemo (98% in each arm). 19 patients crossed over to P-E-Pl. Among 124 patients who started treatment, grade _3 adverse events were observed in 43 vs 36%, while only 2 patients (1 in each arm) had grade 5 toxicity. Among PP patients, 107 PD or deaths were observed. The response rate was 61% (67 vs 56%). Median follow-up time with respect to OS was 14.2 months in EXP and 14.0 months in CTRL arm. Median PFS (80% CI) was 4.7 months (4.5, 5.3) vs 5.4 (4.9, 5.5), HR ¼ 0.84 (0.65, 1.09) and 1-sided p¼0.194. Median OS (80% CI) was 12.3 months (10.2, 14.5) vs 10.4 (8.5, 11.6), HR ¼ 0.73 (0.54,1.0) and 1-sided p¼0.097.Conclusions: P combined with Pl-E was well tolerated but did not improve PFS over Pl-E in chemo-sensitive patients with ED-SCLC. The OS however showed P combined with Pl-E significantly improved OS at 1-sided 10% level.
CitationBesse B, Menis J, Bironzo P, Gervais R, Greillier L, Monnet I, et al. LBA85 REACTION: A phase II study of etoposide and cis/carboplatin with or without pembrolizumab in untreated extensive small cell lung cancer. Annals of Oncology. 2020;31:S1211-S2.
JournalAnnals of Oncology
TypeMeetings and Proceedings