Treatment-free interval as a determinant of second-line chemotherapy outcomes in extensive-stage small cell lung cancer: a Dutch population-based study.

OBJECTIVE: For patients with recurrence after chemotherapy for extensive-stage small cell lung cancer (SCLC), the length of the chemotherapy-free interval (CFI) may guide the choice of second-line treatment. However, evidence supporting specific CFI thresholds is limited. We investigated the influence of the CFI on the effectiveness of second-line treatment in SCLC patients. METHODS: Patients diagnosed with SCLC in 2022 were selected from the Netherlands Cancer Registry. Cox regression and parametric survival models were used to investigate the association between the type of second-line treatment, the CFI, progression-free survival (PFS) and overall survival (OS). Analyses were adjusted for age, sex, performance status, income, comorbidities, response to first-line treatment, and distant metastases. RESULTS: 261 patients were included: 79 received (30.3%) topotecan, 153 (58.6%) platinum rechallenge, and 29 (11.1%) another systemic treatment. Median PFS was 2.0 and 3.9 months after topotecan and platinum rechallenge, respectively. Median OS was 3.8 and 5.6 months, respectively. Multivariable analyses showed a lower risk of progression for patients with a CFI of 90-179 days receiving platinum rechallenge vs topotecan (hazard ratio (HR): 0.62, 95% confidence interval (95%CI): 0.40-0.95), without a difference in OS (HR: 0.99, 95%CI: 0.65-1.52). Parametric survival models confirmed these results. CONCLUSIONS: For patients with a CFI exceeding 90 days, platinum rechallenge represents a rational second-line treatment strategy. These results remain relevant despite the introduction of first-line chemoimmunotherapy, as a substantial proportion of patients still relapse within 180 days. They are also relevant for healthcare settings where immunotherapy access remains limited or unavailable.