Frontline Treatment for Metastatic EGFR-Mutated NSCLC

Susan Scott, MD The Johns Hopkins Hospital | Rahul Gosain, MD, MBA Wilmot Cancer Institute | Rohit Gosain, MD Roswell Park Comprehensive Cancer Center

Key Points

• Overview of standard-of-care treatment options for metastatic EGFR-mutated non-small cell lung cancer.

• Discussing the efficacy and toxicity profiles of the FLAURA2 and MARIPOSA trials.

• Identifying subgroups that derive the most benefit from intensified frontline therapy.

At the 2025 American Society of Clinical Oncology Annual Meeting, Rahul Gosain, MD, MBA, and Rohit Gosain, MD, cohosts of the Oncology Brothers podcast, convened a panel of experts to discuss metastatic EGFR-mutated non-small cell lung cancer (NSCLC).  

 

To start the discussion, Susan Scott, MD, of Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, outlined the current frontline treatment landscape for this patient population.  

  

For several years, osimertinib monotherapy, a third-generation tyrosine kinase inhibitor (TKI), has been the standard-of-care. In 2024, the FDA approved two new combination treatments based on the FLAURA2 and  MARIPOSA trials: osimertinib plus chemotherapy and amivantamab plus lazertinib, respectively.  

 

The FLAURA2 trial found that osimertinib combined with carboplatin-pemetrexed chemotherapy improved progression-free survival (PFS). Final overall survival (OS) data from FLAURA2 are not yet published, but interim analyses have shown positive signals, according to Dr. Scott.  

 

Likewise, the MARIPOSA trial reported improved PFS and OS outcomes with amivantamab in addition to lazertinib—a bispecific antibody against EGFR  and MET and a third-generation TKI, respectively.  

 

Although the FLAURA2 regimen doesn’t add any unfamiliar toxicities, the MARIPOSA regimen is associated with distinct cutaneous toxicities.  

 

In closing, Dr. Scott briefly referenced high-risk subgroups that have shown a benefit with combination strategies, including central nervous system metastases, positive circulating tumor DNA (ctDNA) at baseline, lack of ctDNA clearance, high burden of disease, and TP53  comutation.  

 

With more approved frontline options available, providers must determine which is the best fit for patients with metastatic EGFR-mutated NSCLC.