BEYOND: A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase III Study of First-Line Carboplatin/Paclitaxel Plus Bevacizumab or Placebo in Chinese Patients With Advanced or Recurrent Nonsquamous Non-Small-Cell Lung Cancer

Abstract

Purpose: The phase III BEYOND trial was undertaken to confirm in a Chinese patient population the efficacy seen with first-line bevacizumab plus platinum doublet chemotherapy in globally conducted studies.

Patients and methods: Patients age ≥ 18 years with locally advanced, metastatic, or recurrent advanced nonsquamous non-small-cell lung cancer (NSCLC) were randomly assigned to receive carboplatin (area under the curve, 6) intravenously and paclitaxel (175 mg/m(2)) intravenously (CP) on day 1 of each 3-week cycle, for ≤ six cycles, plus placebo (Pl+CP) or bevacizumab (B+CP) 15 mg/kg intravenously, on day 1 of each cycle, until progression, unacceptable toxicity, or death. The primary end point was progression-free survival (PFS); secondary end points were objective response rate, overall survival, exploratory biomarkers, safety.

Results: A total of 276 patients were randomly assigned, 138 to each arm. PFS was prolonged with B+CP versus Pl+CP (median, 9.2 v 6.5 months, respectively; hazard ratio [HR], 0.40; 95% CI, 0.29 to 0.54; P < .001). Objective response rate was improved with B+CP compared with Pl+CP (54% v 26%, respectively). Overall survival was also prolonged with B+CP compared with Pl+CP (median, 24.3 v 17.7 months, respectively; HR, 0.68; 95% CI, 0.50 to 0.93; P = .0154). Median PFS was 12.4 months with B+CP and 7.9 months with Pl+CP (HR, 0.27; 95% CI, 0.12 to 0.63) in EGFR mutation-positive tumors and 8.3 and 5.6 months, respectively (HR, 0.33; 95% CI, 0.21 to 0.53), in wild-type tumors. Safety was similar to previous studies of B+CP in NSCLC; no new safety signals were observed.

Conclusion: The addition to bevacizumab to carboplatin/paclitaxel was well tolerated and resulted in a clinically meaningful treatment benefit in Chinese patients with advanced nonsquamous NSCLC.

Trial registration: ClinicalTrials.gov NCT01364012.