As of May 2024, follow-up and exploratory analyses of MARIPOSA show improvements in outcomes for patients with EGRF-mutated non–small cell lung cancer (NSCLC).
Carlos Gil Ferreira, MD, PhD, president of the Oncoclinicas Institute and chief medical officer at Oncoclinicas in Brazil, discussed updated data from the MARIPOSA (NCT04487080) study in a session at the 2024 World Conference on Lung Cancer (WCLC), held from September 7 to September 10 in San Diego, California. Ferrerira highlighted a longer follow-up to the study and an exploratory analysis of the study.1
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“Results from MARIPOSA [showed] that the median follow-up initially was 22 months. Amivantamab [Rybrevant; Janssen Biotech Inc] plus lazertinib [Lazcluze; Janssen Biotech Inc] significantly improved progression-free survival [PFS],” Ferreira said. “An early interim analysis of overall survival [OS] showed a favorable trend for amivantamab and lazertinib over osimertinib.”1
In September 2023, positive topline results from the study showed that the combination had statistically significant and clinically meaningful improvements in PFS as first-line treatment for patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) with EGFR mutation. The initial trial included 1074 patients in a randomized open-label study with secondary endpoints of OS, objective response rate (ORR), duration of response (DOR), intracranial PFS, PFS after first subsequent therapy (PFS2), and time-to-symptomatic progression.2
“Previously, we heard . . . that amivantamab plus lazertinib was superior in terms of response rates [and] progression-free survival, although at that point not statistically significant,” said Alex Spira, MD, PhD, FACP, FASCO, a medical oncologist with Virginia Cancer, in an interview. “At WCLC this week, we actually saw data showing that [OS] is now starting to hit statistical significance. So, we can feel fairly comfortable that no matter how you look at it and how you slice and dice it, the combination is more effective.”3
Trial Name: A Study of Amivantamab and Lazertinib Combination Therapy Versus Osimertinib in Locally Advanced or Metastatic Non-Small Cell Lung Cancer (MARIPOSA)
ClinicalTrials.gov ID: NCT04487080
Sponsor: Janssen Research & Development LLC
Completion Date (Estimated): June 2027
As of May 2024, the median follow-up reached 31.1 months, with 44% of patients in the combination arm and 34% in the osimertinib arm still continuing treatment. Approximately 75% of individuals in both groups initiated subsequent therapy, and carboplatin-pemetrexed was the most common subsequent therapy across both arms at 26% and 28%, respectively.1
PFS2 favored the combination therapy at 57% compared with osimertinib at 49%. Further, intracranial PFS showed favorable trends at 28% and 18%, respectively, and duration of response at 51% and 0%, respectively. Median OS was not estimated for amivantamab and lazertinib, but investigators reported OS for osimertinib was 37.3 months.1
In the exploratory study, investigators assessed lazertinib compared with osimertinib, which included 645 patients with 216 receiving lazertinib and 429 receiving osimertinib. The exploratory end points included PFS, ORR, DOR, OS, and safety. Investigators found that the ORR was 83% with lazertinib and 85% with osimertinib, with 16.6 month and 16.8 month DOR, respectively. At the interim survival analysis, the median OS could not be estimated for either arm.1
For the exploratory analysis, which included high-risk patients, patients with brain metastases had median PFS of 16.4 months with lazertinib compared with 13 months for osimertinib. Further, investigators reported that with detectable circulating tumor DNA at baseline, patients had a PFS of 18.4 months compared with 14.8 months, respectively, and with TP53 co-mutations, PFS of 14.6 months and 12.9 months, respectively.1
“The efficacy and safety were similar for both drugs, and even the treatment-related adverse events leading to discontinuation was exactly the same,” Ferreira said. “But the best option for first-line treatment of patients [with metastatic EGFR disease] remains to be determined, and, probably, we will have different options according to the profile of the patients.”1
