Dr Levy on Individualizing Frontline Treatment Escalation in EGFR-Mutant NSCLC

"I do think you have to start looking at co-alterations in [TP53], looking at [circulating tumor DNA], [and] certainly brain [metastases]. This is a group [for whom] I would really favor an escalation strategy if I can."

Benjamin P. Levy, MD, an associate professor of oncology at Johns Hopkins School of Medicine and clinical director of medical oncology at the Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital, discussed how he selects patients with EGFR-mutant non-small cell lung cancer (NSCLC) for first-line osimertinib (Tagrisso) monotherapy vs an intensified regimen and the role of high-risk features.

Levy said he still wrestles with deciding which patients can receive single-agent osimertinib. He considers monotherapy for older patients, those with an ECOG performance status leaning toward 2, those with a lower disease burden, and those who do not want chemotherapy, he noted. Although age should not be used as an independent factor, his patients in their 80s experience more toxicities with osimertinib regardless of performance status, making him hesitant to add chemotherapy, he explained. Based on these criteria, approximately 30% of his patients still receive osimertinib alone, and the rest receive an escalated regimen, Levy said.

He has largely escalated with the regimen utilized in the phase 3 FLAURA2 trial (NCT04035486), citing his familiarity with carboplatin and pemetrexed and the ease of an every-3-week schedule, Levy noted. Although amivantamab (Rybrevant) plus lazertinib (Lazcluze) is potentially more toxic, he said the subcutaneous formulation of amivantamab has been a game changer for the agent, and new dosing schedules may make the combination more palatable for patients and physicians.

Levy added that TP53 co-alterations, baseline brain metastases, and high circulating tumor DNA (ctDNA) levels are prognostic indicators of worse outcomes, as subset data have shown. He has leaned toward escalation for these patients recently, he said.

Still, the decision comes down to shared decision-making, Levy emphasized. He described a patient in with an EGFR mutation, a TP53 co-mutation, and 2 brain metastases who declined chemotherapy since he works multiple jobs, despite understanding the potential benefit. Patient preference cannot be taken lightly, as long as patients understand the trade-offs, Levy concluded.