Dr Shum on Evolving First-Line Treatment Approaches for EGFR-Mutant NSCLC

“Thankfully, there are so many first-line options now for patients with stage IV EGFR-mutated lung cancers. Honestly, we still aren’t sure exactly what the best regimens we should be referring patients to are. There are a lot of data coming out every day that sometimes skew what we do one day to the next, but the most important thing so far is certainly about efficacy.”

Elaine Shum, MD, an assistant professor in the Department of Medicine at NYU Grossman School of Medicine, as well as director of Cancer Screening Programs at NYU Langone Health, discussed clinical decision-making factors regarding first-line therapy for patients with EGFR-mutant non–small cell lung cancer (NSCLC).

The optimal first-line treatment strategy for patients with stage IV EGFR-mutated NSCLC remains an evolving area of investigation, Shum began. Fortunately, the therapeutic paradigm has significantly expanded over recent years, offering multiple treatment options, she said. However, there remains uncertainty regarding the most effective regimen to recommend, and emerging data influence clinical decision-making on an ongoing basis, she noted.

At present, therapeutic efficacy remains a primary consideration. The oncology community is anticipating the full overall survival data readout from the phase 3 FLAURA2 trial (NCT04035486) of osimertinib (Tagrisso) with or without chemotherapy, which are expected to further inform treatment strategies, according to Shum. Relevant data from the phase 3 MARIPOSA trial (NCT04487080) of amivantamab-vmjw (Rybrevant) plus lazertinib (Lacluze) vs osimertinib have previously been reported, and outcomes from the phase 3 FLAURA trial (NCT02296125) evaluating osimertinib monotherapy have also helped frame treatment decision-making, she explained. Nevertheless, these regimens have not been compared in head-to-head clinical trials, she cautioned. As such, selection between these treatment options requires careful patient-provider discussions, particularly regarding differences in toxicity profiles, anticipated adverse effects, and logistical considerations like treatment administration schedules and monitoring burden, Shum stated. These factors are critical in shaping treatment recommendations, especially when considering monotherapy vs combination regimens, she emphasized.

Additionally, certain high-risk clinical and molecular features may influence the selection of more intensive therapeutic approaches, Shum reported. For instance, the presence of brain metastases at diagnosis, or co-occurring genomic alterations like TP53 mutations, may be indicative of a more aggressive disease phenotype, she continued. These factors are integrated into the clinical decision-making process when evaluating the appropriateness of combination therapies, Shum concluded.