Nintedanib plus Chemotherapy for Small Cell Lung Cancer with Comorbid Idiopathic Pulmonary Fibrosis.

Rationale: A fatal acute exacerbation (AE) occasionally develops during chemotherapy for small-cell lung cancer (SCLC) with comorbid idiopathic pulmonary fibrosis (IPF). Objectives: This study aimed to assess the safety and efficacy of carboplatin, etoposide, and nintedanib combination therapy for unresectable SCLC with comorbid IPF. Methods: The NEXT-SHIP study is a multicenter, single-arm, phase 2 trial for unresectable SCLC with IPF (registry number: jRCTs031190119). The patients received carboplatin, etoposide, and nintedanib (150 mg BID). The primary endpoint was the incidence of IPF-AE at 28 days after last administration of cytotoxic chemotherapy, and the sample size was set at 33 (5.0% expected, 20.0% threshold). Measurements and Main Results: A total of 33 patients were registered; 87.9% were male, the median age was 73 years, the median %FVC was 85.2 %, and 51.5% had honeycomb lungs. The median observation period was 10.5 months. The incidence of IPF-AE at 28 days after last administration of cytotoxic chemotherapy was 3.0% (90% confidence interval [CI]: 0.2-13.6). The objective response rate was 68.8% (95% CI: 50.0-83.9). The median progression free survival and overall survival times were 4.2 months (95% CI: 4.2-5.5) and 13.4 months (95% CI 8.1-21.6), respectively. The most common adverse event ≥ grade 3 was neutropenia (81.8%), followed by leukopenia (39.4%) and thrombocytopenia (30.3%). Conclusions: This study met its primary endpoint regarding the incidence of IPF-AEs with promising results for efficacy. Carboplatin, etoposide, and nintedanib combination therapy may be one of the standard treatment options for SCLC with comorbid IPF. Clinical Trial Registration: jRCTs031190119.