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EGFR TKI–Based Combos Could Lead to More Tailored First-Line Treatment Options in EGFR-Mutated NSCLC

*July 2022*

Leveraging EGFR TKIs as a backbone for combination therapies will be pivotal for expanding treatment options and delivering more personalized therapies in the first-line setting for patients with non–small cell lung cancer (NSCLC) harboring EGFR mutations, according to Marina Garassino, MD.

Single-agent osimertinib (Tagrisso) remains the standard of care for patients with EGFR exon 19 and 21 mutations after data from clinical trials showed the EGFR TKI improved progression-free survival (PFS) and penetrated the central nervous system. However, combinations under investigation could further shift the treatment paradigm, Garassino noted.

“In the future, we have to tailor our treatments based on different types of mutations, the presence of comutations, and the clearance of DNA. There is a lot of work [being done] for this research,” said Garassino, a professor of medicine, hematology and oncology, in the Department of Medicine at The University of Chicago.

In April 2018, the FDA approved osimertinib as a first-line treatment for patients with NSCLC whose tumors harbor EGFR exon 19 deletions or exon 21 L858R mutations.2

The approval was based on data from the phase 3 FLAURA trial (NCT02296125) in which osimertinib elicited a median PFS 18.9 months (95% CI, 15.2-21.4), vs 10.2 months (95% CI, 9.6-11.1) for standard TKI therapy with erlotinib (Tarceva) or gefitinib (Iressa; HR, 0.46; 95% CI, 0.37-0.57; P < .001).3 “There were no subgroups that did not benefit from treatment with osimertinib,” Garassino said.

Additional data showed the median overall survival (OS) with osimertinib was 38.6 months (95% CI, 34.5-41.8), compared with 31.8 months (95% CI, 26.6-36.0) in the comparator arm (HR, 0.80; 95.05% CI, 0.64-1.00; P = .046).4

Beyond osimertinib, other third-generation EGFR TKIs have displayed single-agent efficacy as a first-line treatment, Garassino explained. Aumolertinib was evaluated vs gefitinib in the phase 3 AENEAS trial (NCT03849768) for the treatment of patients with NSCLC harboring EGFR exon 19 deletions or L858R mutations. Patients in the aumolertinib arm achieved a median PFS of 19.3 months (95% CI, 17.8-20.8) compared with 9.9 months (95% CI, 8.3-12.8) for those in the gefitinib arm (HR, 0.46; 95% CI, 0.36-0.60; log-rank P < .0001).5

“One [question] is if you can use third-generation TKIs [such as aumolertinib] as [we use] osimertinib, or if we need to have head-to-head comparisons, in particular [among] these drugs developed in Asian countries,” Garassino noted. Read more.