MARIPOSA-2: Amivantamab and Chemotherapy in EGFR-Mutant NSCLC in Second Line and Beyond

This is a synopsis of a Peer Exchange video series featuring Benjamin P. Levy, MD, of Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Solange Peters, MD, PhD, of University Hospital of Lausanne; Joshua K. Sabari, MD, of NYU Langone’s Perlmutter Cancer Center; Edward B. Garon, MD, MS, of UCLA Jonsson Comprehensive Cancer Center; and Marina Chiara Garassino, MD, of University of Chicago Medicine Comprehensive Cancer Center.

In a continued discussion between Dr Joshua K. Sabari, assistant professor of medicine at NYU Langone Health, and other speakers about treatment options after progression on the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib for non–small cell lung cancer (NSCLC), concerns were raised about the toxicity of combination regimens. Dr Sabari notes that while the phase 3 MARIPOSA-2 trial adding carboplatin, pemetrexed, the anti-EGFR antibody amivantamab, and the EGFR TKI lazertinib to chemotherapy nearly doubled progression-free survival in the post-osimertinib setting from 4 to 8 months, there is increased toxicity, especially rash and skin effects.

Another speaker agreed, noting enthusiasm for amivantamab in the frontline setting but concerns combining multiple agents in later lines of therapy given toxicity, which could limit adoption. The speaker felt personalized therapy should be prioritized when possible, rather than a “kitchen sink” approach of adding on agents without clear rationale. Immunotherapy with checkpoint inhibitors alone or with anti-angiogenics was also discussed but has shown limited survival benefit in this setting to date. The role of lazertinib was questioned given similar efficacy of amivantamab and chemotherapy without lazertinib in MARIPOSA-2. CNS activity was considered a potential benefit of lazertinib.

A European speaker highlighted differences in practice patterns, with more chemotherapy combinations used in the United States versus Europe after osimertinib failure. Access to clinical trials and repeat biopsies were also discussed as limitations for some practitioners in providing optimal sequencing for this heterogeneous patient population. Ultimately, while research may continue to explore combinations in this setting, toxicity concerns could limit their adoption, especially in community settings, pointing to a need for safer and more effective options for patients with NSCLC progressing on osimertinib. Even in specialized centers, challenges remain in selecting additional targeted agents for individual patients based on specific resistance mechanisms without clear standard guidelines. Speakers concurred that these limitations must inform new therapeutic strategies to better serve patients with NSCLC in later treatment lines.

*Video synopsis is AI-generated and reviewed by OncLive editorial staff.