Stephen Liu, MD, Weighs in on MARIPOSA Overall Survival Data

Stephen Liu, MD, of the Georgetown University School of Medicine and Georgetown’s Lombardi Comprehensive Cancer Center in Washington, DC, joined Lung Cancers Today to discuss the recent announcement that the phase 3 MARIPOSA trial met its final pre-specified secondary endpoint of overall survival (OS).

The randomized study has been evaluating amivantamab-vmjw (RYBREVANT®) plus lazertinib (LAZCLUZE™) versus osimertinib (TAGRISSO®) 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.

“We’ve known since 2023 that the combination offered a better progression-free survival, a longer period of initial control,” Dr. Liu explained. “But what was in question was the impact on overall survival. What we learned from this announcement is that combination indeed did lead to a longer survival, a substantial improvement in survival.”

The improvement in median OS with amivantamab-vmjw plus lazertinib is estimated to be over a year, which is “a significant improvement over our prior standard,” Dr. Liu said.

“While osimertinib is an excellent treatment, while response rates are very high, while responses occur quickly and are very deep, they are transient, with a median progression-free survival of 18.9 months in the phase 3 trial and certainly shorter for certain subgroups,” Dr. Liu said. “We’ve been looking for something different for many years and these combination strategies, such as MARIPOSA, really did offer an improvement in progression-free survival.”

Progression-free survival as assessed by blinded independent central review was the primary endpoint of the MARIPOSA trial, with OS being one of multiple secondary endpoints. Dr. Liu explained the implications of the new OS data for sequencing and treatment selection in this population of patients.

“When we think of how to process these data, this announcement that survival was better with this MARIPOSA regimen, it supports the fact that being more aggressive upfront really alters the history… survival is a hard endpoint and looks at the treatment sequence in totality,” Dr. Liu said. “Overall, knowing that patients did receive subsequent therapies, seeing such a significant improvement in survival gives a lot of credibility to the fact that being more aggressive upfront may pay dividends in the future.”

The combination of amivantamab-vmjw plus lazertinib was approved in August 2024 in the United States as a first-line treatment for patients with EGFR-mutated NSCLC and was based on the phase 3 MARIPOSA study.

Dr. Liu explained that there are numerous considerations surrounding regimen selection for this patient population, with pursuing the MARIPOSA regimen or osimertinib being a “very individual decision,” based on multiple factors.

“Now we know that patients in that combination arm lived longer—lived a lot longer—and that does change the calculus and will make these conversations a lot more complex,” he said, noting that once full OS results are released, it will be important to understand how or if OS varies across different subsets of patients.

The full results are expected to be presented at a major medical meeting and shared with global health authorities, according to Johnson & Johnson officials.