Chemoimmunotherapy Versus Chemotherapy for Extensive-Stage Small Cell Lung Cancer in the Real-World Setting:...

Small-cell lung cancer (SCLC) is an aggressive malignancy accounting for approximately 15% of all lung cancers, with over 70% of patients diagnosed at the extensive stage (ES). Phase III studies have shown significantly improved overall survival (OS) with the addition of PD-(L)1 inhibitors to platinum-based chemotherapy (CT), establishing chemoimmunotherapy (CIT) as the new first-line standard. This study investigates the real-world efficacy of CIT compared to alternative first-line regimens in patients with ES SCLC.

In this retrospective study, we analyzed 904 patients with newly diagnosed ES SCLC treated at a specialized thoracic cancer center between 2010 and 2022. The primary endpoints were OS and progression-free survival (PFS). Secondary endpoints included the impact of baseline brain metastases (BM), brain and thoracic radiotherapy (RT), and immune-related adverse events (irAEs).

CIT (n = 203) resulted in longer OS than both platinum-based CT (n = 530) and nonplatinum CT (n = 171; median OS 10.2 vs. 9.4 vs. 3.6 months, P < .001). PFS under CIT and platinum-based CT was significantly longer compared to nonplatinum CT (median PFS 5.3 vs. 5.6 vs. 2.6 months, P < .001). Compared to platinum-based CT, CIT significantly reduced the risk of death or progression (OS HR 0.73, 95% CI, 0.62-0.87; P < .001; PFS HR 0.79, 95% CI, 0.67-0.93; P = .006), whereas nonplatinum CT was associated with a 2x higher risk (OS HR 2.19, 95% CI, 1.84-2.61; PFS HR 2.28, 95% CI, 1.91-2.72; both P < .001). Thoracic RT was an independent predictor of longer survival across the entire cohort (OS HR 0.57, 95% CI, 0.48-0.69; P < .001 in multivariable analysis [MVA] including sex, age, ECOG performance status, type of systemic treatment, and presence of baseline BM). While the presence of BM at diagnosis was prognostically neutral, brain RT among patients with baseline BM was also associated with longer survival (OS HR 0.47, 95% CI, 0.35-0.65; P < .001 in MVA). Immune-related adverse events (iAEs) were associated with longer OS and PFS (OS HR 0.67, 95% CI, 0.46-0.97; P = .032; PFS HR 0.68, 95% 0.47-0.97; P = .035 in MVA), while treatment discontinuation due to irAEs did not compromise survival.

Chemoimmunotherapy confers a clear OS advantage over conventional chemotherapy in real-world ES-SCLC. Local radiotherapy is associated with additional survival improvement, while the occurrence of irAEs may correlate with treatment efficacy.