Front-Line Therapy Options for the Treatment of EGFR + Lung Cancer

In a session presented at the virtual 2020 Personalized Therapies in Thoracic Oncology meeting, Gregory J. Riely, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, provided an overview of the current front-line treatment landscape for patients with EGFR-positive lung cancer.

“This is an area where we’ve seen a lot of advances over the past 5 or 6 years, and I hope to show you some advances that we may see going forward,” he told listeners.

In looking at patients with EGFR-positive lung cancer, it’s important to remember that there are multiple molecular subtypes of the disease based on genotypes, including ALK, ROS1, and BRAF.

Notably, EGFR was the first genotype recognized as being targetable in this setting.

Data have shown that EGFR tyrosine kinase inhibitors (TKIs) are better for patients with EGFR-positive lung cancer than platinum-based doublets. In randomized trials of gefitinib, erlotinib, and afatinib, the TKIs yielded better progression-free survival (PFS) rates than chemotherapy, although there weren’t any significant overall survival (OS) advantages.

“Despite the success with EGFR TKIs, we know that patients develop acquired resistance,” Dr Riely said, who shared an example of a study in which gefitinib initially yielded better results than chemotherapy, but later yielded rates of progression.

The mechanism of resistance in patients who have received first-line first- or second-generation TKIs is T790M, the discovery of which has led to the development of third-generation EGFR TKIs, the most notable of which is osimertinb.

While the first- and second-generation EGFR TKIs targeted the common sensitizing mutations of L858R and Exon 19 del, they also targeted wild-type EGFR, which leads to many toxicities observed with EGFR TKIs.

Although third-generation EGFR TKIs are less effective in targeting wild-type EGFR, they do hit T790M in addition to EGFR exon 19 deletion and EGFR L858R, with osimertinib demonstrating superiority to platinum-based chemotherapy in patients with EGFR T790M.

“For patients with EGFR exon 19 deletion and EGFR L858R, based on improvements in PFS and OS compared with gefitinib/erlotinib, first-line therapy with osimertinib is standard of care. There are current explorations to improve upon osimertinib, including the addition of bevacizumab or ramucirumab, as well as addition of chemotherapy to osimertinib,” Dr Riely summarized.

“Although EGFR exon 20 insertion were previously considered not sensitive to available EGFR targeted therapy, there new agents are in development for these patients, and we look forward to seeing their results,” he concluded.—Hina Porcelli

Riely GJ. Front line EGFR Treatment options. Presented at: Personalized Therapies in Thoracic Oncology; October 1-2, 2020; virtual.