Efficacy and safety of oral vinorelbine with concurrent radiotherapy in unresectable stage III non-small cell lung cancer following neoadjuvant chemoimmunotherapy: a single-arm, phase 2 trial.

Background: Individuals with unresectable stage Ⅲ non-small cell lung cancer (NSCLC) who receive complete concurrent chemoradiotherapy (cCRT) can benefit from long-term survival. Although neoadjuvant chemoimmunotherapy (NACIT) have achieved breakthroughs in treating unresectable stage Ⅲ NSCLC, patients who have received induction chemoimmunotherapy are considered poor candidates for cCRT due to concerns about tolerability. Oral vinorelbine chemotherapy is widely used in clinical settings because of its safety, even for frail patients. The objective of this trial was to assess the efficacy and safety of oral vinorelbine plus concurrent radiotherapy (RT) for individuals with unresectable stage Ⅲ NSCLC following NACIT who were not candidates for concurrent intravenous chemotherapy. Methods: This was a single-arm, phase 2 trial. The primary endpoint was the objective response rate (ORR), while the secondary endpoints consisted of the disease control rate (DCR), safety, overall survival (OS), as well as progression-free survival (PFS). Results: Between March 10, 2023 and April 24, 2025, 46 individuals with unresectable stage Ⅲ NSCLC were administered oral vinorelbine plus thoracic RT. Patients were treated with oral vinorelbine (60 mg/m2 once a week for 2 weeks as induction therapy before thoracic RT) and 30 mg/m2 per week with concurrent RT (59.4-60.2 Gy) over 5.5 weeks. The median age of the patients was 62.5 years, with 42 being male (91.3 %). The ORR was 52.1 % (95 % confidence interval [CI], 35.1 %-65.9 %), with 24 partial responders. A 95.7 % DCR (85.5 %-98.8 %) was observed, and 20 patients had stable disease. The median follow-up was 22.5 months; the median PFS was 18.0 months and the median OS was not reached. The most commonly observed adverse events (AEs) included leukopenia (grade 1, 26.1 %), anemia (grade 1, 17.4 %), neutropenia (grade 1, 10.9 %), acute esophagitis (grade 2, 17.4 %), and treatment-related pneumonitis (grade 1-2, 60.9 %). No grade 3 or 4 treatment-related AEs were recorded. Conclusion: In individuals with unresectable stage Ⅲ NSCLC who had received NACIT and were not candidates for concurrent intravenous chemotherapy with RT, the oral vinorelbine plus concurrent RT demonstrated promising antitumor efficacy with acceptable toxicity profiles. Trial registration: ClinicalTrials.gov (NCT06540950).