Highlights in NSCLC From the 2014 ASCO Meeting

A phase 2 study evaluated whether NSCLC patients with EGFR mutations might benefit from dual VEGF/EGFR inhibition in the first-line setting (Abstract 8005). The trial enrolled chemotherapy-naive NSCLC patients with nonsquamous, stage IIIB/IV or recurring disease and an activating EGFR mutation (del19 or L858R). Patients had a performance status of 0 or 1 and no brain metastases. They were randomized evenly to receive erlotinib (150 mg daily) or erlotinib plus bevacizumab (15 mg/kg every 3 weeks). The primary endpoint was PFS by independent review. Secondary endpoints included OS, tumor response, safety, quality of life, and symptom improvement. The study recruited 154 patients from 30 institutions, although 2 patients in the combination arm withdrew before they received treatment. At the time of data cutoff, 103 PFS events had been observed. Baseline characteristics were well balanced between the 2 arms. Patients had a median age of 67 years, and nearly two-thirds were female. More than half of the patients had never smoked, and approximately 53% had the del19 EGFR mutation. The study met its primary endpoint, demonstrating a significant improvement in median PFS with the addition of bevacizumab to erlotinib (16.0 months vs 9.7 months; HR, 0.54; 95% CI, 0.36-0.79; P=.0015). For the group of patients with del19, bevacizumab plus erlotinib yielded a median PFS of 18.0 months vs 10.3 months for erlotinib alone (HR, 0.41; 95% CI, 0.24-0.72). For patients with the L858R mutation in exon 21, combination treatment yielded a median PFS of 13.9 months compared with 7.1 months for erlotinib alone (HR, 0.67; 95% CI, 0.38-1.18). AEs of grade 3 or higher were more common in patients receiving the combination treatment than erlotinib monotherapy (91% vs 53%, respectively). However, serious AEs occurred in approximately one-fourth of patients in each arm. AEs of grade 3 or greater that occurred at a significantly higher rate with the combination treatment vs placebo included hypertension (60% vs 10%, respectively) and proteinuria (8% vs 0%, respectively).