Dr. Girard Shares Key Insights on MARIPOSA Final Overall Survival Data

Nicolas Girard, MD, PhD, of Institut Curie in Paris, France, joined Lung Cancers Today to discuss and share insights on the final overall survival (OS) data from the phase 3 MARIPOSA trial, which is being presented at the 2025 European Lung Cancer Congress (ELCC).

The study evaluated amivantamab plus lazertinib versus osimertinib as a first-line treatment for patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) with EGFR exon 19 deletions or L858R substitution mutations. The trial previously met its primary end point of progression-free survival, and an interim OS analysis of the trial showed “favorable OS trends” for amivantamab plus lazertinib versus the current standard of care, osimertinib.

“At ELCC 2025, we have the final overall survival analysis results from MARIPOSA, demonstrating a significant benefit overall with amivantamab plus lazertinib versus osimertinib,” Dr. Girard said. “From the statistical analysis and the lower boundary of the confidence interval, we expect the magnitude of difference in overall survival to be higher than 12 months, which is highly significant in clinical practice.”

With a median follow-up of 37.8 months, the combination treatment demonstrated a hazard ratio (HR) of 0.75 for death compared with osimertinib (95% CI, 0.61-0.92; P<0.005). The study findings indicated that the median OS was not estimable among patients who received amivantamab plus lazertinib, Dr. Girard said, emphasizing that “assuming an exponential distribution of OS in both arms,” amivantamab plus lazertinib “is anticipated to prolong median OS by at least 12 months versus osimertinib.”

Dr. Girard explained that these OS results address critical questions about optimal treatment sequencing in this setting and suggest that “we are modifying the natural biological history of the disease.”

“If we start upfront with the combination with amivantamab plus lazertinib, we not only prolong the duration and the efficacy of first-line, but also this benefit translates into an overall survival benefit,” he said. “It means that amivantamab plus lazertinib in the first-line setting is impacting the whole treatment sequence.”

Dr. Girard explained that these results “further establish” amivantamab plus lazertinib as the “new standard of care” for this patient population.

“With the overall survival data, we expect more patients to receive this combination,” he said.

Dr. Girard also reflected on the implications for patients and the associated advancements, such as the development of prophylactic measures in the COCOON trial.

“When the first clinical trials with amivantamab and lazertinib started, it was a rapid development from phase 1 to phase 3, and we had to learn in between how to better manage the side effects,” he concluded. “The MARIPOSA data clearly shows that we can do better, and this data clearly shows how we can transform the outcomes of patients. We thought that osimertinib would be the standard of care forever—this is not the case. It’s possible to improve the patients’ survival.”

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