Adding Pembrolizumab to First-Line Chemotherapy Fails to Improve Survival in Extensive SCLC
Key Clinical Takeaways
- Design/Population: The phase 2 REACTION trial randomized 125 patients with chemo-sensitive extensive disease-SCLC who responded to 2 cycles of platinum-etoposide to pembrolizumab plus chemotherapy or chemotherapy alone. The trial evaluated PFS as the primary end point, with OS and circulating tumor cell analyses as key secondary and exploratory measures
- Key Outcomes: Pembrolizumab did not improve median PFS compared with platinum-etoposide alone (4.7 vs 5.4 months) and was associated with a higher rate of grade ≥3 adverse events. OS trends numerically favored pembrolizumab but did not reach statistical significance.
- Clinical Relevance: These findings suggest that pembrolizumab does not provide additional benefit in chemo-sensitive extensive disease-SCLC beyond platinum-etoposide alone. Circulating tumor cell counts may represent a valuable prognostic biomarker for future risk stratification strategies.
Results from the phase 2 REACTION trial demonstrate that the addition of pembrolizumab to first-line platinum-etoposide does not improve survival among chemo-sensitive patients with extensive small cell lung cancer (SCLC).
“Anti-PD-L1 antibodies with platinum-etoposide extend overall survival of extensive disease [SCLC] patients,” stated Jessica Menis, MD, University Hospital of Verona, Italy, and coauthors. Here, “we evaluated the benefit of first-line pembrolizumab with platinum-etoposide in chemo-sensitive [extensive disease] SCLC.”
In this open-label trial, 125 patients who achieved disease control after 2 cycles of platinum-etoposide were randomized 1:1 to receive platinum-etoposide alone (n = 64) or pembrolizumab plus 4 additional cycles of platinum-etoposide followed by pembrolizumab maintenance (n = 61). The primary end point was progression-free survival (PFS). Key secondary end points included response rate, overall survival (OS), and safety. Investigators also evaluated the association between circulating tumor cell (CTC) count and survival outcomes.
At analysis, median PFS was 4.7 months in the control arm and 5.4 months in the pembrolizumab arm (P = .194). Response rates were 67% and 56%, respectively. Median OS was 12.3 months in the control arm and 10.4 months in the pembrolizumab arm (P = .097). Baseline CTC count per 7.5 mL of blood was significantly associated with both PFS and OS, independent of treatment arm. Grade ≥3 adverse events occurred in 26% of patients in the control arm and 37% of patients in the pembrolizumab arm.
As Dr Menis et al concluded, “pembrolizumab added to platinum-etoposide did not improve PFS over platinum-etoposide alone in chemo-sensitive patients with [extensive disease].”
Source:
Menis J, Greiller L, Demontrond P, et al. EORTC 1417 - REACTION: A phase II study of etoposide and cis/carboplatin with or without pembrolizumab in untreated extensive small cell lung cancer. Eur J Cancer. Published online: October 29, 2025. doi:10.1016/j.ejca.2025.116059
