SCLC is characterized by large number of CTCs that have demonstrated prognostic value. We evaluated CTC count and PD-L1 expression on CTCs in the REACTION trial, a multicenter, open-label, randomized phase II trial.
In the REACTION 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 a total of 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. CTCs were collected with Streck tubes after registration and during the first 2 cycles of induction chemotherapy (at the discretion of the investigator), before randomization and every 2 cycles during treatment and at end of treatment.
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 = 0.84 (0.65, 1.09) and 1-sided p=0.194. Median OS (80% CI) was 12.3 months (10.2, 14.5) vs 10.4 (8.5, 11.6), HR = 0.73 (0.54, 1.0) and 1-sided p=0.097.
P combined with Pl-E was well tolerated, did not improve PFS but OS was significantly improved. CTC analysis are in finalization and results will be presented during the congress.
Clinical trial identification
Legal entity responsible for the study
European Organization for Research and Treatment of Cancer.
Merck Sharp & Dohme.
All authors have declared no conflicts of interest.