Selecting Among Preferred 1L Regimens — A Discussion

Drs. Goldberg and Nagasaka discuss how to choose among the three NCCN category 1 preferred first-line regimens — amivantamab plus lazertinib, osimertinib monotherapy, and osimertinib plus chemotherapy — for patients with EGFR-mutated advanced NSCLC. Dr. Nagasaka frames the choice as shared decision-making, beginning with tumor-level risk factors such as brain or liver metastases, baseline ctDNA shedding, and TP53 co-mutation, and then incorporating the patient’s preferences regarding lifestyle, work, and tolerability. She notes that osimertinib monotherapy retains familiarity and a favorable tolerability profile, while the two combination regimens add survival benefit at the cost of greater toxicity, and that the differences in adverse event profiles between amivantamab plus lazertinib and osimertinib plus chemotherapy often guide the conversation more than efficacy alone.

On patients with stable brain metastases, Dr. Nagasaka emphasizes that all three regimens have CNS data but that the protocol-mandated serial MRIs in MARIPOSA give that dataset particular reliability. For asymptomatic baseline brain metastases, she leans toward an intensified regimen rather than osimertinib monotherapy. Dr. Goldberg agrees that brain involvement often pushes her toward a combination regimen. Both discuss strategies for keeping patients on combination therapy long-term. Dr. Nagasaka recommends proactive prophylaxis, family and caregiver involvement, and early referrals. Dr. Goldberg adds that she introduces the possibility of dose interruption or reduction up front, so that subsequent adjustments are framed as expected rather than as a treatment failure.

In the next episode, "From PALOMA-3 to PALOMA-2 Cohort 5: SC Q4W Dosing Evidence," Dr. Nagasaka walks through the subcutaneous formulation, the route and interval evolution, and the Cohort 5 efficacy results.