Survival outcomes with carboplatin versus cisplatin and the impact of COVID-19 on platinum choice: A nationwide Netherlands registry study in small cell lung cancer patients (CACIS)

Background: Guidelines recommend cisplatin as the preferred platinum agent in the first-line treatment for small cell lung cancer (SCLC), especially limited-stage disease (LS-SCLC). However, during the COVID-19 pandemic, carboplatin use likely increased due to logistical advantages. We evaluated the pandemic's impact on platinum agent utilization in the Netherlands and compared overall survival (OS) and safety between cisplatin and carboplatin. Methods: Using Netherlands Cancer Registry data, first-line platinum-based treatments for LS-SCLC and extensive-stage SCLC (ES-SCLC) between 2018 and 2023 were analyzed. OS was evaluated using univariable and multivariable analyses. Grades 3–5 treatment-related adverse events were studied in three hospitals. Findings: Overall, 1683 LS-SCLC (carboplatin, N = 1011[60 %]; cisplatin, N = 672[40 %]) and 3668 ES-SCLC (carboplatin, N = 3002[82 %]; cisplatin, N = 666[18 %]) patients were included. During the pandemic, quarterly usage rates of carboplatin reached up to 81 % and 90 % in LS-SCLC and ES-SCLC, respectively. In LS-SCLC, univariable analysis showed significantly shorter median OS with carboplatin compared to cisplatin (17.9m vs. 26.3m; HR, 1.48; 95 %CI, 1.31–1.68; p < 0.001). Similar findings were observed in ES-SCLC (8.0m vs. 9.3m; HR, 1.19; 95 %CI, 1.09–1.30; p < 0.001). However, multivariable analyses, after adjusting for confounders, showed no significant OS differences in either LS-SCLC (HR, 1.06; 95 %CI, 0.90–1.25; p = 0.463) or ES-SCLC (HR, 1.01; 95 %CI, 0.92–1.12; p = 0.785). Confounders were performance status (PS), age, sex, and chemoradiotherapy type for LS-SCLC, and PS, age, sex, stage, and liver metastases for ES-SCLC. Hematologic toxicity was higher with carboplatin, while cisplatin led to more nonhematologic toxicity. Interpretation: These findings challenge the long-standing belief of cisplatin's superiority and support the adoption of carboplatin in SCLC.