Efficacy and safety of crizotinib plus bevacizumab in positive non-small cell lung cancer: an open-label, single-arm, prospective observational study.

BACKGROUND

Crizotinib is a tyrosine kinase inhibitor (TKI) effective in positive non-small cell lung cancer (NSCLC) patients. Bevacizumab is an antiangiogenic monoclonal antibody, and improves clinical benefit of NSCLC in combination with EGFR-TKIs or chemotherapy. However, the efficacy and safety of crizotinib plus bevacizumab in treating naive positive NSCLC patients have not been studied.

METHODS

In this open-label, single-arm, prospective observational study, locally advanced or metastatic rearrangement/ fusion/ amplification NSCLC patients were treated with crizotinib (250 mg orally twice daily) and bevacizumab (7.5 mg/kg intravenous every three weeks) until disease progression or intolerant toxicity or death. Primary end point was progressive free survival (PFS), secondary end points were duration of response (DOR), overall response rate (ORR), disease control rate (DCR) and safety. Patients receiving ≥1 cycle of treatment were evaluated.

FINDINGS

Fourteen patients were eligible for analyzing between June 2016 and October 2017. There were 12 patients with rearrangement, 1 patient with fusion, and 1 patient with amplification. The median follow-up time was 42.8 months. The median PFS and DOR of the patients with rearrangement were 13.9 and 14.8 months respectively. Of the 12 patients, 7 gained partial response, 5 gained stable disease. The ORR and DCR were 58.3% and 100%. The PFS were 12.9 months and 1.9 months for patient with fusion or amplification. The most two common treatment-related adverse events were fatigue (28.6%) and rash (21.4%). 3 patients discontinued therapy because of liver damage or hemoptysis.

INTERPRETATION

This study demonstrated that crizotinib plus bevacizumab showed benefit in treating naive rearrangement NSCLC patients, and the toxicity was relatively tolerant. Our results suggested that crizotinib plus bevacizumab might be a promising treatment strategy in positive NSCLC patients.