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

To assess the feasibility of adding bevacizumab consolidation into hypo-fractionated concurrent chemoradiotherapy (hypo-CCRT) in patients with unresectable locally advanced non-squamous non-small cell lung cancer (LA-NS-NSCLC). Eligible patients were treated with hypo-RT (40 Gy in 10 fractions) followed by hypo-boost (24-28 Gy in 6-7 fractions) combined with concurrent weekly chemotherapy. Patients completed the hypo-CCRT without≥G2 toxicities then received consolidation bevacizumab every 3 weeks for up to 1 year, or disease progression or unacceptable treatment related toxicities. The primary endpoint was the risk of G4 or higher hemorrhage. The secondary endpoint was 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. From December 2017 to July 2020, a total of 27 patients were analyzed with a median follow-up duration of 28.0 months. One patient (3.7%) developed G5 hemorrhage during bevacizumab consolidation. Besides, there were 7 patients (25.9%) had G3 cough and 3 patients (11.1%) had G3 pneumonitis. The ORR was 92.6% of the whole cohort. 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. 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 G3 respiratory toxicities is worth considering.