Invited discussant of the BOOSTER trial,1 Edward B. Garon, MD, MS, Professor of Medicine and Director of the Thoracic Oncology Program, David Geffen School of Medicine at the University of California Los Angeles, said the study’s research question is appropriate, since osimertinib was established as the standard of care for patients with EGFR T790M mutations and disease progression on prior EGFR tyrosine kinase inhibitors. In the pivotal study by Jänne et al,2 the response rate in evaluable patients was, he said, “obviously impressive,” and responses were durable.
“There has long been interest in adding an antiangiogenic agent to an EGFR inhibitor,” stated Dr. Garon. To this end, the focus has been on bevacizumab and ramucirumab (and to a lesser extent, some other agents). In the BOOSTER trial, however, the addition of bevacizumab to osimertinib was not superior to osimertinib alone, and the hypothesized hazard ratio was outside the 95% confidence interval. Findings reflect those of a smaller, similarly designed study from Japan,3 whose hazard ratio was 1.44 favoring single-agent osimertinib, he noted.
Edward B. Garon, MD, MS
Although in the BOOSTER trial some benefit from the combination appeared to emerge in smokers, Dr. Garon questioned the strength of those findings, since smoking was not a stratification factor in this trial or a factor commonly examined in such studies. “I think this finding is hypothesis-generating and may help in future studies,” he noted.
Areas of Investigation
Of greater interest today may be the combination of osimertinib (or other EGFR tyrosine kinase inhibitors) plus an anti-VEGF agent in the front-line setting, continued Dr. Garon. The combination of bevacizumab and erlotinib as first-line therapy was approved in Europe based on data sets from Japan, and some countries have approved erlotinib plus ramucirumab.
“There have been questions as to whether osimertinib can help salvage patients who had good outcomes but experienced disease progression on erlotinib and an angiogenic or gefitinib and chemotherapy. That has led to enthusiasm about combining osimertinib with either bevacizumab or ramucirumab in the front-line setting,” Dr. Garon commented.
Although that is an active area of investigation, Dr. Garon said he sees “few data that are particularly supportive of” osimertinib plus an angiogenesis inhibitor. “I know there are ongoing studies in this setting,” he said, “but I think there is room for studies exploring other approaches in this setting.”
DISCLOSURE: Dr. Garon has served as a consultant or advisor to ABL Bio, Boehringer Ingelheim, Bristol Myers Squibb, Dracen, Eisai, EMD Serono, GlaxoSmithKline, Merck, Novartis, Sanofi, Shionogi, and Xilio Therapeutics; and has received institutional research funding from AstraZeneca, Bristol Myers Squibb, Dynavax, EMD Serono, Genentech, Iovance Biotherapeutics, Lilly, Merck, Mirati Therapeutics, Neon Therapeutics, and Novartis.
REFERENCES
1. Soo R, Han JY, Dimopoulou G, et al: A randomized phase II study of second-line osimertinib and bevacizumab versus osimertinib in advanced non-small cell lung cancer with epidermal growth factor receptor and T789M mutations: Results from the ETOP BOOSTER trial. ESMO Virtual Plenary. Abstract VP3-2021. Presented May 12, 2021.
2. Jänne PA, Yang J CH, Kim DW, et al: AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N Engl J Med 372:1689-1699, 2015.
3. Akamatsu H, Toi Y, Hayashi H, et al: Efficacy of osimertinib plus bevacizumab vs osimertinib in patients with EGFR T790M-mutated non-small cell lung cancer previously treated with epidermal growth factor receptor-tyrosine kinase inhibitor: West Japan Oncology Group 8715L phase 2 randomized clinical trial. JAMA Oncol 7:386-394, 2021.
