A pilot trial of consolidation bevacizumab after hypo-fractionated concurrent chemoradiotherapy in patients with unresectable locally advanced non-squamous non-small-cell lung cancer

Abstract

Purpose: To determine the feasibility of incorporating bevacizumab consolidation into hypo-fractionated concurrent chemoradiotherapy (hypo-CCRT) for patients with unresectable locally advanced non-squamous non-small-cell lung cancer (LA-NS-NSCLC).

Patients and methods: Eligible patients were treated with hypo-RT (40Gy in 10 fractions) followed by hypo-boost (24-28Gy in 6-7 fractions), along with concurrent weekly chemotherapy. Patients who completed the hypo-CCRT without experiencing ≥G2 toxicities received consolidation bevacizumab every 3 weeks for up to 1 year, until disease progression or unacceptable treatment-related toxicities. The primary endpoint was the risk of G4 or higher hemorrhage. Secondary endpoints included progression-free survival (PFS), overall survival (OS), locoregional failure-free survival (LRFS), distant metastasis-free survival (DMFS), and objective response rate (ORR). All time-to-event endpoints (OS, PFS, LRFS, and DMFS) were measured from the start of radiotherapy.

Results: Between December 2017 and July 2020, a total of 27 patients were included in the analysis, with a median follow-up duration of 28.0 months. One patient (3.7%) developed G5 hemorrhage during bevacizumab consolidation. Additionally, seven patients (25.9%) had G3 cough and three patients (11.1%) experienced G3 pneumonitis. The ORR for the entire cohort was 92.6%. The median OS was 37.0 months (95% confidence interval, 8.9-65.1 months), the median PFS was 16.0 months (95% confidence interval, 14.0-18.0 months), the median LRFS was not reached, and the median DMFS was 18.0 months.

Conclusions: This pilot study met its goal of demonstrating the tolerability of consolidation bevacizumab after hypo-CCRT. Further investigation of antiangiogenic and immunotherapy combinations in LA-NSCLC is warranted, while the potential for grade 3 respiratory toxicities should be taken into consideration.

Keywords: LA-NS-NSCLC; consolidation bevacizumab; hypo-CCRT; treatment-related toxicity.