Bevacizumab–Erlotinib Combo Trumps Erlotinib Monotherapy in EGFR-Positive NSCLC

Interim phase 3 study findings show that combining bevacizumab therapy with erlotinib improved progression-free survival (PFS) over erlotinib alone in patients with EGFR-positive non–small-cell lung cancer (NSCLC; Lancet Oncol. 2019 Apr 8. Epub ahead of print).

“The JO25567 phase 2 trial comparing erlotinib plus bevacizumab combination therapy with erlotinib monotherapy established the activity and manageable toxicity of erlotinib plus bevacizumab in patients with NSCLC,” explained lead investigator Haruhiro Saito, MD, Kanagawa Cancer Center, Yokohama, Japan, and colleagues.

To validate findings from the JO25567 study, they conducted NEJ026, a phase 3 trial, and subsequently reported their interim analysis outcomes.

Between June 3, 2015, and August 31, 2016, a total of 228 patients with stage IIIB to IV or recurrent, nonsquamous, EGFR-positive NSCLC were enrolled and randomized to receive erlotinib plus bevacizumab (n = 114) or erlotinib alone (n = 114). The primary end point of the study is PFS, and although NEJ026 is ongoing, the data cutoff for the interim analysis was September 21, 2017.

Ultimately, 112 patients in each arm were evaluable for efficacy, and safety was evaluated in 112 and 114 in the combination and monotherapy arms, respectively. Follow-up lasted for a median of 12.4 months, and as of the interim analysis, the median PFS for patients receiving erlotinib plus bevacizumab was 16.9 months (95% CI, 14.2-21.0) versus 13.3 months (95% CI, 11.1-15.3) with erlotinib (hazard ratio, 0.605; 95% CI, 0.417-0.877; P = .016).

Of 112 patients in the erlotinib plus bevacizumab arm, 98 (88%) had adverse events grade ≥3; the same was observed for 53 (46%) of 114 patients in the erlotinib-alone arm. Rash was the most common grade 3-4 adverse event, occurring in 23 (21%) of 112 patients in the erlotinib plus bevacizumab arm and 24 (21%) of 114 patients in the erlotinib-alone arm.

There were no treatment-related deaths reported.

“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,” Dr Saito and colleagues concluded.

“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,” they added.—Hina Khaliq