MARIPOSA Trial: Revolutionizing First-Line Treatment for EGFR-Mutated NSCLC

Key Discussion Points from Dr. Girard's Video

• Overview of MARIPOSA Trial [0:19-0:54]
• Clinical Practice Implications [0:54-1:32]
• Final Overall Survival Analysis at #ELCC25 [1:30-2:30]
• Treatment Sequence Impact and Biological Basis [2:32-3:10]
• Management of Side Effects [3:51--4:28]
  

Overview of MARIPOSA Trial

Nicolas Girard, MD, PhD, of Institut Curie in Paris, France reviewed with Lung Cancers Today on YouTube. compelling data from the MARIPOSA trial, which evaluated amivantamab plus lazertinib versus osimertinib for first-line treatment in EGFR-mutated non-small cell lung cancer.  The primary endpoint of progression-free survival (PFS) by blinded independent committee review was successfully met. Amivantamab plus lazertinib significantly extended PFS from 17 months with osimertinib to 24 months, with a hazard ratio of 0.70, demonstrating substantial clinical benefit.

Clinical Practice Implications

The critical question facing clinicians is determining the optimal treatment sequence. Dr. Girard highlighted several potential approaches: starting with osimertinib followed by amivantamab plus chemotherapy (MARIPOSA-2 regimen), initiating treatment with amivantamab plus lazertinib, or considering other options such as chemotherapy plus osimertinib. Dr. Girard emphasized that overall survival is a crucial metric that reflects the entire treatment sequence.

Final Overall Survival Analysis

At ELCC 2025, the final overall survival analysis from MARIPOSA demonstrated significant benefits with amivantamab plus lazertinib versus osimertinib, with a hazard ratio of 0.75. The historical median overall survival with osimertinib was 37 months, while the median overall survival with amivantamab plus lazertinib has not yet been reached. Dr. Girard mentioned that the statistical analysis indicates the magnitude of difference in overall survival is expected to exceed 12 months, representing a clinically significant improvement.

Treatment Sequence Impact

Dr. Girard emphasized that initiating treatment with amivantamab plus lazertinib not only prolongs first-line efficacy but also translates into an overall survival benefit. This suggests that amivantamab in the first-line setting impacts the entire treatment sequence. Biological data regarding resistance mechanisms indicates that the combination modifies the natural biological progression of the disease. Dr. Girard emphasized that the MARIPOSA data clearly demonstrates improved outcomes for patients, challenging the notion that osimertinib would remain the standard of care indefinitely.

Management of Side Effects

As with any new treatment regimen, clinicians have had to develop strategies to manage side effects associated with amivantamab plus lazertinib. Dr. Girard noted that prophylactic measures have been implemented to address dermatologic side effects (COCOON protocol) and infusion-related reactions (SKIPPirr protocol). He drew a parallel to the development of anti-emetic regimens for chemotherapy, highlighting that standardized prophylactic measures are now being established for amivantamab to optimize patient care and tolerability.