A secondary analysis of the phase 3 MARIPOSA trial presented at the 2024 ASCO Annual Meeting reveals that the combination of amivantamab and lazertinib significantly improves progression-free survival (PFS) compared to osimertinib in patients with high-risk, EGFR-mutant advanced non-small cell lung cancer (NSCLC). The study highlights the potential of this combination as a new first-line treatment option for this patient population.
The MARIPOSA trial included 858 treatment-naïve patients with EGFR-mutant (exon 19 deletion or L858R) advanced NSCLC, with 89% exhibiting at least one high-risk feature such as brain or liver metastases, TP53 co-mutations, or detectable circulating tumor DNA (ctDNA). Patients were randomized 1:1 to receive either amivantamab plus lazertinib (n = 429) or osimertinib (n = 429).
Significant PFS Improvement
The blinded independent committee review determined that the median PFS in the amivantamab/lazertinib arm was 23.7 months (95% CI, 19.1-27.7), compared to 16.6 months in the osimertinib arm (95% CI, 14.8-18.5; HR = 0.70; P < .01). This represents a 30% reduction in the risk of disease progression or death and a 7.1-month improvement in median PFS.
Impact of TP53 Co-mutations
Among patients with a TP53 co-mutation, the median PFS was 18.2 months in the combination group (n = 149) and 12.9 months in the osimertinib group (n = 144; HR, 0.65; p = 0.002). In patients whose disease was TP53 wildtype, there was a trend favoring amivantamab/lazertinib, with a median PFS of 22.1 months compared to 19.9 months (HR = 0.75; P = .11).
ctDNA Analysis
In patients with ddPCR-detectable ctDNA at baseline, the median PFS was significantly longer in the amivantamab/lazertinib arm (n = 231) compared to the osimertinib arm (n = 240), at 20.3 months and 14.8 months, respectively (HR = 0.68; P = .002). At baseline, 69% and 71% of patients in the amivantamab/lazertinib arms, respectively, had detectable EGFR-mutant ctDNA, which decreased to 15% in each group at week 9.
The combination also showed superiority in patients with ctDNA clearance at cycle 3 day 1, with median PFS durations of 24 months (n = 163) vs 16.5 months (n = 180), respectively (HR = 0.64; P = .004), and in patients who did not clear ctDNA, at 16.5 months (n = 29) vs 9.1 months (n = 32), respectively (HR = 0.49; P = .015).
Outcomes in Patients with Metastases
For patients with brain metastases at baseline, amivantamab/lazertinib led to improved outcomes, with a median PFS of 18.3 months (95% CI, 16.6-23.7) compared to 13 months (95% CI, 12.2-16.4) for osimertinib (HR = 0.69; P = .010). Similarly, in patients with liver metastases, the median PFS was 18.2 months (95% CI, 13.1-NE) and 11 months (95% CI, 7.4-12.8; HR = 0.58; P = .017) in the amivantamab/lazertinib groups, respectively.
Expert Commentary
Enriqueta Felip, MD, PhD, head of the Thoracic and Head and Neck Cancer Unit at Vall d’Hebron Hospital in Barcelona, Spain, noted that high-risk features are common in first-line EGFR-mutant NSCLC and are associated with poor prognosis. She concluded that amivantamab plus lazertinib produces superior PFS outcomes in patients with these high-risk features, representing a promising new standard of care treatment option.
