The efficacy and safety of chemo‐free therapy in epidermal growth factor receptor tyrosine kinase inhibitor‐resistant advanced non‐small cell lung cancer: A single‐arm, phase II study

OBJECTIVES: The purpose of this study was to explore the efficacy and safety of toripalimab combined with anlotinib in patients with advanced non‐small cell lung cancer (NSCLC) who acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs). MATERIALS AND METHODS: Patients who developed resistance after using first‐ or second‐generation EGFR‐TKIs as their first‐line regimen without EGFR T790M mutation or had disease progression after being treated with third‐generation EGFR‐TKIs as first‐ or second‐line therapy were enrolled. All patients received toripalimab (240 mg/day on Day 1, intravenously) combined with anlotinib (12 mg/day, Days 1–14, orally) once every 3 weeks. Treatment continued until disease progression, or if toxicity was intolerable. The primary endpoint was the objective response rate (ORR) assessed by the investigator. The secondary endpoint was the progression‐free survival (PFS). RESULTS: In total, 19 patients were enrolled between May 2020 and October 2021.The ORR was 0%, and a median PFS was 2.1 months (95% CI 0.251–3.949). Grade ≥3 treatment‐related adverse events (AEs) occurred in 11% patients. Common adverse events included hypothyroidism (12/19), fatigue (9/19), and hypertension (8/19). Patients in stable disease (SD) group had lower abundance of EGFR mutation allele frequency (AF) before enrollment than those in progressive disease (PD) group (p = 0.031). Patients without detectable EGFR mutation (EGFR−) had longer PFS compared to the ones with EGFR mutations (p = 0.059). Patients with high levels of soluble programmed cell death ligand 1 (PD‐L1) at baseline also tended to have longer PFS (p = 0.160). CONCLUSION: Toripalimab combined with anlotinib was tolerable in EGFR‐TKI‐resistant advanced NSCLC patients not previously treated with chemotherapy. Patients without detectable EGFR mutation and high soluble PD‐L1 levels may benefit from this chemotherapy‐free treatment.