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.