Makoto Maemondo, MD
In an interim analysis of the phase III NEJ026 trial reported in The Lancet Oncology, Makoto Maemondo, MD, and colleagues found that the addition of bevacizumab to erlotinib improved progression-free survival in patients with EGFR-positive, nonsquamous non–small cell lung cancer (NSCLC).
In the open-label multicenter trial, 224 patients in the modified intent-to-treat population (those who received ≥ 1 dose of study drug and had ≥ 1 response evaluation out of 228 randomly assigned patients) were randomly assigned between June 2015 and August 2016. Patients received either oral erlotinib at 150 mg per day plus bevacizumab at 15 mg/kg once every 21 days (n = 112) or erlotinib at 150 mg per day (n = 112). Patients had at least stage IIIB or IV or postoperative recurrent nonsquamous NSCLC with activating EGFR genomic aberrations and no previous therapy for advanced disease.
The primary endpoint was progression-free survival in the modified intent-to-treat population. The study is ongoing; the data cutoff for the prespecified interim analysis reported here was in September 2017.
Median follow-up was 12.4 months. Median progression-free survival was 16.9 months in the erlotinib plus bevacizumab group vs 13.3 months in the erlotinib group (hazard ratio [HR] = 0.605, P = .016). Subgroup analysis by EGFR aberration type indicated a significant benefit of erlotinib/bevacizumab in the 113 patients with a Leu858Arg mutation (median = 17.4 vs 13.7 months, HR = 0.57, 95% confidence interval [CI] = 0.33–0.97), whereas the numeric benefit among 111 patients with exon 19 deletions did not reach statistical significance (median = 16.6 vs 12.4 months, HR = 0.69, 95% CI = 0.41–1.16). Objective response was observed in 72% vs 66% of patients (P = .31).
Grade ≥ 3 adverse events occurred in 88% of the erlotinib/bevacizumab group and 46% of the erlotinib-alone group, with the most common in the erlotinib/bevacizumab group being hypertension (23% vs 1%) and rash (21% vs 21%). Serious adverse events occurred in 8% vs 4% of patients, including 2 patients with grade 4 neutropenia and 1 with grade 4 hepatic dysfunction in the erlotinib/bevacizumab group. No treatment-related deaths were reported.
The investigators concluded, “The results of this interim analysis showed that bevacizumab plus erlotinib combination therapy improves progression-free survival compared with erlotinib alone in patients with EGFR-positive NSCLC. Future studies with longer follow-up, and overall survival and quality-of-life data will be required to further assess the efficacy of this combination in this setting.” ■