Combination Therapy: A New Frontline Standard in the Treatment of EGFR-Mutant NSCLC

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Key Considerations for Selecting EGFR Inhibitor Treatment in Non–Small Cell Lung Cancer

Panel Introduction

• Moderator:Zosia Piotrowska, MD, MHS: Thoracic medical oncologist at Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
• Expert Panelist:Martin Dietrich, MD, PhD: Medical oncologist with the US Oncology Network, Orlando, Florida

Panel Expertise

Both experts are thoracic oncologists specializing in the treatment of non–small cell lung cancer (NSCLC), with particular focus on targeted therapies for EGFR-mutated disease.

First-Line Treatment Options for EGFR-Mutated NSCLC

Key Themes:

• Evolving Treatment Landscape: Recent clinical trials have shifted the standard of care from osimertinib monotherapy to combination approaches.
• Current Treatment Options: Discussion of NCCN guidelines listing osimertinib monotherapy as preferred Category 1, with combination therapies (FLAURA2 regimen of osimertinib plus chemotherapy and MARIPOSA regimen of amivantamab plus lazertinib) as other recommended options.
• Paradigm Shift: Both experts agree that combinations now outperform monotherapy, particularly for high-risk patients.

Notable Insights:

• Dr Dietrich: “We’ve seen 2 large phase 3 studies that have shown superiority to osimertinib, our gold standard for the better part of a decade.” He noted that the MARIPOSA trial demonstrated “a clinically quite remarkable overall survival benefit of 12 months.”
• Dr Piotrowska: While agreeing on the superiority of combinations, she emphasized that osimertinib monotherapy remains appropriate for certain patients, particularly “older patients with limited supports, those with impaired kidney function” or patients who “want to maximize quality of life and minimize time in the clinic.”