MARIPOSA: Amivantamab Plus Lazertinib Delays Time to Symptomatic Progression in EGFR-Mutated NSCLC

Amivantamab and lazertinib “significantly delayed” time to symptomatic progression (TTSP) compared with osimertinib in patients with previously untreated, advanced, EGFR-mutated non-small cell lung cancer (NSCLC), according to an analysis of the MARIPOSA study.

Danny Nguyen, MD, of the City of Hope National Medical Center, and colleagues, conducted the analysis and published their findings in the European Journal of Cancer.

The combination of amivantamab and lazertinib combination therapy previously demonstrated “improved progression-free survival (PFS) and overall survival (OS)” compared with osimertinib in the MARIPOSA trial, according to the study authors.

Dr. Nguyen and colleagues explained that the TTSP measure, which “provides an easily interpretable measure of disease-specific symptom worsening to further support patient experience,” was “introduced to assess clinical worsening and complement end points that investigate radiographic disease progression and patient-reported outcomes.”

They quantitatively assessed TTSP as a secondary efficacy end point in MARIPOSA and defined TTSP “as the time from randomization until participants experience disease-specific symptom worsening requiring a clinical intervention or treatment change, or death,” according to the publication. They conducted an exploratory analysis censoring deaths to “evaluate the impact of amivantamab and lazertinib on TTSP considering its established OS benefit against osimertinib,” Dr. Nguyen and colleagues explained.

The median TTSP was 43.6 months with amivantamab plus lazertinib and was 29.3 months in those receiving osimertinib (hazard ratio [HR], 0.69; 95% CI: 0.57–0.83; P<.001) at the final protocol-specified OS analysis, which had a median follow-up of 37.8 months.

“Amivantamab and lazertinib reduced deaths following a TTSP event compared to osimertinib,” Dr. Nguyen and colleagues explained, noting that “a strong correlation between TTSP and PFS or OS was observed.”

Based on these findings, Dr. Nguyen and colleagues conclude that TTSP provides “complementary insights alongside traditional end points” and that it “enhances understanding of treatment benefit and supports informed clinical decision-making by integrating patient experience.”