Multicenter cohort study of second-line strategies for extensive-stage SCLC with brain-only progression after first-line treatment

The optimal second-line strategy for patients with extensive-stage small cell lung cancer (ES-SCLC) developing brain-only progression (BOP) after first-line therapy is not clear. A cohort study at three centers in China evaluated the efficacy of continuing the original systemic therapy versus switching strategies for these patients. A total of 203 patients developing BOP after first-line therapy were assigned to 3 second-line strategies: continuation of original systemic therapy plus brain radiotherapy (OTP + BRT; n=71), substitution systemic therapy plus BRT (ST + BRT; n=64), or substitution systemic therapy alone (ST; n=68). IPTW was used to balance baseline characteristics. The primary endpoint was overall survival from second-line initiation (OS2). The figure shows the results of the analyses. OTP + BRT demonstrated significantly superior median OS2 (14.7 months) compared with ST (10.2 months; HR 1.68; p=0.028) and ST + BRT (9.8 months; HR 1.67; p=0.023). OTP + BRT also yielded improved median second-line progression-free survival (8.0 months) versus ST (4.0 months; p=0.024). Multivariable analysis confirmed OTP + BRT as an independent prognostic factor for improved survival. The benefit was most pronounced in patients with prior immunotherapy and longer initial progression-free survival (≥ 7.5 months). No significant survival differences were observed among radiotherapy modalities (WBRT versus SRT). The authors conclude that for ES-SCLC patients with BOP, continuing the original systemic regimen plus BRT yields superior survival compared with switching systemic therapy.