Ep. 2: CNS Control and Resistance: Panel Examines Amivantamab Plus Lazertinib
Joshua Sabari, MD, of NYU Langone Health, led the panel discussion toward central nervous system (CNS) efficacy. Segueing into this topic, Edgardo Santos, MD, FACP, FASCO, of the Oncology Institute of Hope and Innovation, described how MARIPOSA’s prospective MRI-based design allows precise measurement of intracranial progression-free survival, demonstrating approximately doubled CNS control at 3 years compared with osimertinib alone.
Danny Nguyen, MD, of City of Hope, emphasized that enhanced CNS penetration, combined with coverage of MET-mediated resistance, may underlie the improved outcomes. Alexander Spira, MD, PhD, FACP, FASCO, of NEXT Oncology, noted that FLAURA2 also demonstrates CNS activity, though MARIPOSA’s structured follow-up provides more granular data.
Clinical Relevance of CNS Coverage
The panelists highlighted the importance of CNS coverage in patient quality of life. Eric Singhi, MD, of The University of Texas MD Anderson Cancer Center, referenced institutional data showing that over 50% of EGFR-positive patients develop CNS metastases within 5 years, underscoring the need for therapies that prevent neurological complications.
The discussion turned to patients with liver metastases, TP53 co-mutations, and other high-risk features. Dr. Santos indicated that combination therapy shows benefits across subgroups, with potentially greater effects in patients with high-risk features.
Balancing Efficacy With Patient Priorities
Shared decision-making remains essential. Dr. Spira emphasized discussing risks, benefits, and patient priorities, tailoring therapy based on lifestyle considerations and desired clinic visit frequency. Dr. Sabari noted that these conversations guide escalation versus de-escalation strategies.
Implications for Up-Front Treatment Strategies
The panel concluded that CNS activity and high-risk subgroup data reinforce the rationale for up-front combination therapy. Continued evaluation of MARIPOSA and FLAURA2 will inform individualized treatment decisions and refine long-term care strategies.