Frontline Treatment Options in EGFR-Mutated NSCLC Show Promise

Christine Bestvina, MD, an associate professor of medicine at the University of Chicago, spoke with CancerNetwork® about how she believes that there have been a lot of positive, exciting advancements in frontline EGFR-mutated non–small cell lung cancer (NSCLC).

The phase 3 MARIPOSA trial (NCT04487080) evaluating amivantamab-vmjw (Rybrevant) and lazertinib (Lacluze) and the phase 3 FLAURA2 trial (NCT04035486) evaluating osimertinib (Tagrisso) with or without chemotherapy.^1,2 Both studied patients who had untreated EGFR-mutated advanced NSCLC.

In the MARIPOSA trial, the experimental regimen elicited a median progression-free survival (PFS) of 23.7 months when compared with 16.6 months from osimertinib alone (HR, 0.70; 95% CI, 0.58-0.85; P <.001). In the FLAURA2 trial, the median follow-up for PFS was 19.5 months in the osimertinib and chemotherapy group and 16.5 months in the osimertinib alone group.

One of the major questions still facing the physician community, however, is how to decide which patients need escalated therapy. It could be patients with an L858R mutation, with baseline brain metastasis, or with a significant burden of disease, Bestvina noted.

Transcript:

The frontline [EGFR-mutated NSCLC] space is exciting right now. We’ve seen promising results thus far from both the MARIPOSA [regimen] as well as the FLAURA2 regimen, in addition to what we previously had, which is osimertinib monotherapy. We’re still trying to understand what patients need escalated therapy, whether that’s osimertinib plus chemotherapy or amivantamab plus lazertinib in the front line because there are patients who do not perform as well despite having an EGFR mutation. Is that patients who have an L858R mutation? Is that patients with baseline brain metastasis? Are those patients who have a significant burden of disease? I’m discussing these more aggressive or escalated treatment options with patients right now, but we need some longer-term overall survival data to help discuss with patients what is the best treatment of choice for them.

References

1. Cho BC, Lu S, Felip E, et al. Amivantamab plus lazertinib in previously untreated EGFR-mutated advanced NSCLC. N Engl J Med. 2024;391(16):1486-1498. doi:10.1056/NEJMoa2403614
2. Planchard D, Jänne PA, Cheng Y, et al. Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med. 2023;389(21):1935-1948. doi:10.1056/NEJMoa2306434