MARIPOSA Analysis: Amivantamab Plus Lazertinib Is ‘Important New Standard of Care’ for Certain Patients With NSCLC

Patients with biomarkers of high-risk disease who received amivantamab plus lazertinib for treatment-naïve, EGFR-mutated, advanced non-small cell lung cancer (NSCLC) showed improved median progression-free survival (PFS) compared with those receiving osimertinib, according to results from MARIPOSA.

Enriqueta Felip, MD, PhD, of the Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology, and colleagues conducted the study and presented their findings during an oral abstract session held Friday, May 31 at the 2024 American Society of Clinical Oncology Annual Meeting.

The MARIPOSA study previously showed that first-line amivantamab plus lazertinib provided a statistically significantly improvement in PFS compared with osimertinib in patients with EGFR-mutant advanced NSCLC (hazard ratio [HR], 0.70; P<.001), including in patients who had a history of brain metastases (HR, 0.69). MARIPOSA enrolled patients who had treatment-naïve, EGFR-mutated (Ex19del or L858R) advanced NSCLC.

It was important to conduct the subgroup analysis of MARIPOSA to evaluate outcomes for patients with high-risk features such as TP53 co-mutations, detectable circulating tumor DNA (ctDNA), and baseline brain or liver metastases, as these patients typically “have poor prognoses,” according to Dr. Felip and colleagues. The analysis presented at the meeting included patients who were randomized to receive amivantamab plus lazertinib (n=429) or osimertinib (n=429).

The researchers analyzed pathogenic alterations by conducting next-generation sequencing (NGS) on baseline blood ctDNA using Guardant360 CDx. They used the Biodesix droplet digital PCR (ddPCR) to analyze Ex19del and L858R ctDNA in blood at baseline and on day 1 of cycle 3. Baseline ctDNA for NGS analysis was available for 320 patients receiving amivantamab plus lazertinib and 316 of those receiving osimertinib.

The MARIPOSA subgroup analysis showed that in patients with a TP53 co-mutation, the median PFS was 18.2 months in those receiving amivantamab plus lazertinib and 12.9 months in those receiving osimertinib (HR, 0.65; P=.003). In patients with wild-type TP53, there was a “trend favoring” the combination therapy for median PFS (HR, 0.75; P=.11), according to Dr. Felip and colleagues.

In those who had ddPCR-detectable ctDNA at baseline, the combination treatment showed a significantly prolonged median PFS (20.3 months) compared with the median PFS in those receiving osimertinib (14.8 months; HR, 0.68; P=.002). In addition, the combination showed a significant improvement in median PFS (24.0 months) over osimertinib (16.5 months) for patients who showed ctDNA clearance at day 1 of cycle 3 (HR, 0.64; P=.004). The benefit of the combination therapy was also shown in patients who did not clear ctDNA by that time point, with a median PFS of 16.5 months in those receiving amivantamab plus lazertinib, compared with a median PFS of 9.1 months in those receiving osimertinib (HR, 0.48; P=.014).

Among patients who had liver metastases at baseline, the combination therapy significantly prolonged median PFS (18.2 months) compared with osimertinib (11.0 months; HR, 0.58; P=.017). This result is “consistent with the improved PFS” for patients with a history of brain metastases who receive amivantamab plus lazertinib rather than osimertinib.

Dr. Felip and colleagues reflected on the subgroup analysis results, explaining that amivantamab plus lazertinib “demonstrated significantly improved [median] PFS” versus osimertinib in patients with biomarkers of high-risk disease.

“Given these features can occur in up to 85% of [patients, amivantamab plus lazertinib] represents an important new standard of care for treatment-naïve EGFR-mutant advanced NSCLC,” they concluded.

Reference

Felip E, Cho BC, Gutiérrez V, et al. Amivantamab plus lazertinib vs osimertinib in first-line EGFR-mutant advanced non-small cell lung cancer (NSCLC) with biomarkers of high-risk disease: a secondary analysis from the phase 3 MARIPOSA study. Presented at the 2024 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2024; Chicago, Illinois.