Primary feasibility analysis of neoadjuvant chemotherapy with bevacizumab for resectable stage II/IIIA non-squamous non-small cell lung cancer: the NAVAL phase II study.

Abstract

Objectives: Bevacizumab (Bev) improves the response and survival rates in patients with advanced non-small cell lung cancer (NSCLC). This phase II trial aimed to assess the feasibility of adding Bev to preoperative chemotherapy in resectable non-squamous NSCLC.

Methods: Patients with clinical stage II/IIIA non-squamous NSCLC (n = 30) received three cycles of cisplatin (Cis), pemetrexed (Pem), and Bev, followed by surgical resection. The primary endpoint was the complete resection rate (CRR), defined as the proportion of all eligible enrolled patients who ultimately underwent complete (R0) resection. The sample size was set at 30 patients. Treatment was considered feasible if the CRR exceeded the predefined acceptable threshold of 65%.

Results: Radiological tumour reduction was observed in 29 of 30 patients (97%). Twenty-eight patients (93%) completed all three cycles of chemotherapy, and 25 patients (83%) underwent surgery. Five patients discontinued treatment due to adverse events (n = 3), disease progression (n = 1), or patient refusal (n = 1). Complete resection was achieved in all resected patients, yielding an 83% CRR (two-sided 80% confidence interval, 71.3%-91.7%). The objective response rate was 37%, and pathological complete response of the primary tumour was achieved in 3 patients (12%). Grade 3 toxicities included neutropenia (7%), nausea (7%), hypertension (23%), and pulmonary embolism (3%). No grade 4/5 adverse events occurred within 28 days, and no treatment-related deaths occurred within 84 days.

Conclusions: Preoperative Cis, Pem, and Bev for clinical stage II/IIIA non-squamous NSCLC met the predefined feasibility criterion, with acceptable safety in this selected population. These findings provide historical insights supporting perioperative anti-vascular endothelial growth factor-based systemic intensification.