Second-line chemotherapy efficacy is not affected by prior exposure to immunotherapy in extensive-disease small-cell lung cancer: results from the ESME French national real-world cohort
Background Extensive-disease small-cell lung cancer (ED-SCLC) is an aggressive disease with limited effective therapeutic options. Clinical trials suggest an additive effect of chemotherapy and immunotherapy in SCLC, although the magnitude of benefit seems to be limited. Considering the prolonged peripheral persistence of anti-PD-(L)1 blockade, we wanted to investigate the impact of prior immunotherapy exposure on the efficacy of second-line chemotherapy. Patients and methods Using the Epidemio-Strategy and Medical Economics lung cancer national real-world database, we selected ED-SCLC patients diagnosed between 17 February 2010 and 4 December 2023 who had received at least two lines of treatment for a metastatic disease with platinum-based regimens in the first-line setting. Second-line real-world progression-free survival (rw-PFS) and overall survival (OS) were analyzed according to first-line immunotherapy exposure using a multivariable Cox proportional hazards model and a propensity score-weighted sensitivity analysis. Results The study included 2051 patients with ED-SCLC: 638 (30%) in the immunotherapy-pretreated group and 1413 (70%) who received only first-line chemotherapy. Multivariable analysis showed no significant difference in second-line median rw-PFS between immunotherapy-pretreated patients [2.9 months, 95% confidence interval (CI) 2.7-3.3] and chemotherapy-only pretreated patients (2.5 months, 95% CI 2.4-2.7) (hazard ratio 0.94, 95% CI 0.85-1.04, P = 0.21). Similar results were observed in the propensity score adjusted Cox regression sensitivity analysis. A longer median OS from the start of second-line treatment was observed in immunotherapy-pretreated patients (6.6 months, 95% CI 6.1-7.1 compared with 5.7 months, 95% CI 5.4-6.1, P = 0.03) although, this result has not been confirmed in a more contemporary cohort. Conclusion This study showed no OS gain in second-line treatment among patients pretreated with immunotherapy compared with those who received chemotherapy alone as first-line treatment.