Erlotinib plus Bevacizumab Is Safe and Effective in EGFR-Mutant NSCLC

EGFR mutations are common in non–small cell lung cancer (NSCLC) and often confer sensitivity to EGFR inhibitors such as erlotinib; however, resistance eventually develops in most patients. Based on the results of smaller studies that suggest erlotinib may synergize with the VEGF antibody bevacizumab, Zhou, Xu, and colleagues initiated ARTEMIS-CTONG1509, a phase III randomized trial of bevacizumab plus erlotinib versus erlotinib alone in Chinese patients with advanced, newly diagnosed, EGFR-mutant NSCLC. In total, 311 patients were enrolled, with 157 patients receiving the combination treatment, 153 patients receiving erlotinib monotherapy, and one patient randomized to erlotinib alone withdrawing from the study before treatment began. Among all patients treated, the median overall survival (OS) was 36.2 months with the combination treatment and 31.6 months with erlotinib monotherapy. Interestingly, a subgroup analysis revealed that for the 91 patients who had brain metastases at baseline, the median OS was 31.6 months with bevacizumab plus erlotinib and 26.8 months with erlotinib alone. Additionally, in contrast to what has been found in some prior studies, the type of EGFR mutation (exon 19 deletion or L858R substitution) did not appear to affect treatment response. The safety and toxicity profiles were generally as expected, and grade 3 or greater adverse events were more common in the combination therapy group than in the erlotinib-only group, occurring in 54.8% and 26.1% of patients, respectively. Despite the higher prevalence of high-grade adverse events, quality-of-life measures indicated no difference between patients in the two groups: Both sets of patients had quality-of-life scores on treatment comparable to those at baseline. An exploratory analysis of paired baseline–progressive disease samples showed no significant difference in the landscape of acquired resistance mutations between samples in the bevacizumab plus erlotinib group versus the erlotinib-only group. In summary, the results of this trial demonstrate that adding bevacizumab to erlotinib is effective in extending life span and does not negatively affect quality of life in patients with EGFR-mutant, previously untreated NSCLC.

Zhou Q, Xu CR, Cheng Y, Liu YP, Chen GY, Cui JW, Yang N, et al. Bevacizumab plus erlotinib in Chinese patients with untreated, EGFR-mutated, advanced NSCLC (ARTEMIS-CTONG1509): A multicenter phase 3 study. Cancer Cell 2021 Aug 12 [Epub ahead of print].

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