Introduction and Frontline Regimen Selection in EGFR-Mutant NSCLC

May 11, 2026

Post-TTLC 2026: Dr. Sandip Patel (University of California San Diego, Moores Cancer Center) welcomes Dr. Deborah Doroshow (Mount Sinai) for a practical discussion on treatment selection and sequencing in advanced EGFR-mutated non-small cell lung cancer (NSCLC). Dr. Patel frames the conversation around how clinical features, molecular findings, CNS involvement, and real-world treatment burden shape both frontline and post-progression decisions, and how emerging data on resistance, re-biopsy, and antibody-drug conjugate (ADC) approaches are entering practice.

Asked about choosing between FLAURA2 and MARIPOSA, Dr. Doroshow explains that no single feature pulls her toward one regimen. She references an individual patient–level analysis suggesting a possible advantage for FLAURA2 in patients with CNS metastases and for MARIPOSA in TP53-mutant tumors but says she is more often influenced by toxicity profiles and patient preference. She still favors osimertinib monotherapy for patients with borderline performance status, those declining combination therapy, or those with logistical barriers such as living far from the hospital.

Dr. Patel agrees that host factors, tolerance for chemotherapy or cutaneous toxicity, and geographic access drive his choice. He simplifies the conversation around two questions: whether the patient can tolerate the therapy medically and socially, and whether they need an intensified regimen. High tumor burden, CNS metastasis, TP53 co-mutation, liver metastasis, and high cell-free DNA shed favor intensification; lung-only, low-shed disease may favor monotherapy. Both experts discuss circulating tumor DNA (ctDNA) dynamics and acknowledge the field is still learning how to use early ctDNA changes to escalate or de-escalate therapy.