Dr Levy on How the EGFR-Targeted Therapy Landscape Has Evolved in NSCLC

“[I] whittled this down to the question: Is the juice worth the squeeze? And that’s really a question we have to ask for every therapy we now give in lung cancer.”

Benjamin P. Levy, MD, clinical director of Medical Oncology at Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital and associate professor of oncology at Johns Hopkins University School of Medicine, discussed how escalation strategies have reshaped first-line treatment for patients with EGFR-mutated non–small cell lung cancer (NSCLC), and how he balances survival benefit against toxicity, treatment burden, and cost at the the 44th Annual PER® Chemotherapy Foundation Symposium.

Until approximately 2 years ago, the standard of care was single-agent osimertinib (Tagrisso), a third-generation TKI that is superior to first-generation TKIs, Levy said. Since then, 2 escalation strategies have demonstrated superior outcomes in direct comparisons with osimertinib, he explained.

The first, evaluated in the phase 3 FLAURA2 trial (NCT04035486), adds chemotherapy to osimertinib. This regimen adds toxicity, Levy acknowledged, but oncologists are familiar with chemotherapy-related adverse effects.

The second, evaluated in the phase 3 MARIPOSA trial (NCT04487080), pairs lazertinib (Lazcluze), a third-generation TKI similar to osimertinib, with amivantamab (Rybrevant), a bispecific antibody targeting EGFR and MET, Levy explained. Levy described the data for the regimen from the trial as one of the largest survival advantages ever seen in EGFR-mutated lung cancer, with an approximate improvement of 12 months. The challenge with the regimen has been toxicities such as paronychia, rash, and diarrhea, he said, though proactive mitigation strategies are under study in the phase 2 COCOON (NCT06120140) and SKIPPirr (NCT05663866) studies, he underscored.

Treatment selection must be individualized, Levy then emphasized, with every patient deserving a nuanced discussion grounded in shared decision-making. He said that he lays out all options, shares where he is leaning based on his experience, and incorporates the patient’s input, since each patient has a different story and a different propensity for toxicity. This takes more time for physicians, Levy concluded, but that time is needed so patients ultimately benefit.