Immunotherapy and the Sequence Relative to Survival Outcomes in SCLC: Analysis of the National Cancer Database

Abstract

Background: SCLC remains an aggressive malignancy with limited therapeutic progress over the past few decades. It remains unclear how the sequence of immunotherapy initiation influences overall survival (OS) in SCLC; we performed a population-based analysis using NCDB to evaluate its association with survival. Methods: SCLC patients in NCDB from 2016 to 2021 were identified to evaluate the impact of immunotherapy on OS. Among ES-SCLC patients, we conducted subsequent analyses to clarify the relationship between the sequence of immunotherapy initiation and OS in the context of chemotherapy and CRT. Results: Among 69,820 eligible patients, 9242 received CRT plus immunotherapy (CRT + IO), and 11,755 received chemotherapy plus immunotherapy (Chemo + IO). In the overall population, adding immunotherapy to chemotherapy or CRT was associated with modestly improved survival. In ES-SCLC, immunotherapy was associated with longer survival in both the Chemo and CRT cohort, while the addition of immunotherapy did not confer benefits in limited-stage SCLC (LS-SCLC). Within the ES-SCLC Chemo + IO cohort, altering the initiated immunotherapy interval (0–90 days) did not show any meaningful difference in survival. By contrast, in the CRT + IO cohort, survival showed benefit in a time-dependent pattern: patients who initiated immunotherapy within 4–7 days after CRT had a trend of survival, which was consistent with the proposed immune activation window. Conclusions: This real-world analysis suggests that immunotherapy was associated with longer survival in ES-SCLC, CRT + IO is associated with improved OS, with a more obvious survival benefit when immunotherapy is initiated within 4–7 days after CRT. These findings hint at the potential importance of immunotherapy initiation sequence and warrant further prospective validation.