Safety and efficacy of radiotherapy combined with anlotinib in locally advanced non-small cell lung cancer patients intolerant to concurrent chemoradiotherapy: Preliminary result of a phase II clinical trial.

8043 Background: Concurrent chemoradiotherapy (cCRT) is the standard treatment for patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC). However, parts of patients only receive sequential chemoradiotherapy (sCRT) due to various reasons. This phase II study aimed to improve the outcomes of patients receiving sCRT by combining anti-angiogenesis therapy (anlotinib) during radiotherapy course. Methods: Patients with unresectable LA-NSCLC intolerable to cCRT were prospectively enrolled. Induction chemotherapy with or without immunotherapy were given for 4-6 cycles. Then patients were prescribed oral 12 mg anlotinib up for 3 cycles during radiotherapy. The primary endpoint is 2-year overall survival (OS). Acute adverse events (AEs) were defined as any treatment related events from the start of radiotherapy until 3 months post-radiotherapy. The trial has been registered in ChiCTR.org as ChiCTR2200060712. Results: From October 2020 to January 2024, 41 patients with stage II-III NSCLC were enrolled. 11 (26.8%) patients received induction chemotherapy and 30 (73.2%) patients received induction chemotherapy combined with immunotherapy. The rate of grade 3–4 acute hematological AEs was 29.3% (12 cases). The rates of grade 3 hemoptysis were 2.4% (1 case), with no grade 4 hemoptysis reported. The incidence of grade 3–4 radiation pneumonitis was 9.8% (4/41). No grade 5 AEs occurred in all patients. The median follow-up was 16.8 (range: 7.0–50.7) months. 22 (53.7%) patients experienced recurrence, including 5 patients (12.2%) with primary-site recurrence and 7 patients (17.1%) with regional-node recurrence, 12 patients (29.3%) had distant metastases. The median progression-free survival (PFS) was 18.9 months (95%CI 14.6-23.2 months) and 1-year PFS was 77.2%. 9 patients (22.0%) died, including 3 patients who died of covid-19 pneumonia during the follow-up period, 1 patient who died of hydatid pneumonia due to long-term bed rest after cerebral infarction, and 4 patients who died of tumor-related diseases. The 1-year overall survival was 89.9%. Conclusions: Our data first showed the combination of thoracic radiotherapy and anti-angiogenesis therapy (anlotinib) is of safety, well controlled toxicity, and efficacy for inoperable LA-NSCNC patients who cannot tolerate cCRT. Clinical trial information: ChiCTR2200060712 .