Turn toward third-generation drug
“Treatment with a single-agent EGFR-TKI remains the standard of care for patients with EGFR-mutant NSCLC,” Dr. Goldberg and colleagues wrote.
Why the combination of afatinib and cetuximab, which has demonstrated activity in the resistance setting, failed in the first-line setting remains unclear, Dr. Goldberg observed in an interview.
She noted that about one-quarter of patients receiving the afatinib/cetuximab combination discontinued cetuximab because of toxicity.
“That’s a good amount. It could be part of the explanation,” Dr. Goldberg said.
Investigators are currently analyzing collected tissue and blood samples in an effort to identify biomarkers that could potentially predict subgroups receiving benefit.
“That’s our next step: looking at specific EGFR mutation types, comutation types, and amplification of other genes and of EGFR,” Dr. Goldberg said.
She noted that, because of a superior side-effect profile and possibly greater efficacy, osimertinib is being used in the first-line setting.
“So now the idea of combining an EGFR-TKI with an EGFR antibody is still an active area of research, but with osimertinib rather than a first- or second-generation drug,” she said.
This research was supported by Boehringer Ingelheim, Eli Lilly, grants from the National Institutes of Health/National Cancer Institute, The Hope Foundation Career Development Award, and the SWOG and NIH Yale SPORE in Lung Cancer Grant. Dr. Goldberg and colleagues disclosed relationships with many pharmaceutical companies.
SOURCE: Goldberg SB et al. J Clin Oncol. 2020 Oct 6. doi: 10.1200/JCO.20.01149.