The MARIPOSA trial's results indicate that the combination of amivantamab and lazertinib could become a novel first-line treatment for non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations. The study demonstrated a statistically significant improvement in progression-free survival (PFS) compared to osimertinib, the current standard of care. This combination offers a chemotherapy-free option with potential benefits, especially for patients with brain metastases.
Improved Progression-Free Survival
The phase III MARIPOSA trial (NCT04487080) enrolled 1074 patients with locally advanced or metastatic NSCLC who were treatment-naïve and had EGFR exon 19 deletion or L858R point mutations. Patients were randomized to receive either amivantamab plus lazertinib, osimertinib alone, or lazertinib alone. The primary endpoint was PFS.
The combination of amivantamab and lazertinib reduced the risk of progression or death by 30% (HR 0.70, 95% CI 0.58–0.85, p<0.001). Median PFS was 23.7 months (95% CI 19.1–27.7) in the combination arm compared to 16.6 months (95% CI 14.8–18.5) in the osimertinib arm. Lazertinib monotherapy also showed a clinically meaningful PFS of 18.5 months (95% CI 14.8–20.1).
Efficacy in Subgroups
The PFS benefit of amivantamab plus lazertinib was consistent across various subgroups, including age, gender, race, smoking history, brain metastases, and classic EGFR mutations. Notably, in patients with brain metastases, the combination therapy resulted in a median PFS of 18.3 months (95% CI 16.6–23.7) compared to 13.0 months (95% CI 12.2–16.4) with osimertinib.
Safety and Tolerability
The most common treatment-related adverse events in the combination arm included paronychia, infusion-related reactions, rash, hypoalbuminemia, increased ALT, and venous thromboembolism. While the combination therapy had higher rates of EGFR- and MET-related adverse events, the majority were grade 1 or 2. Treatment-related adverse events leading to discontinuation were reported in 10% of patients on amivantamab plus lazertinib and 3% on osimertinib. Grade 3 or higher treatment-related adverse events occurred in 75% of patients on the combination compared to 43% on osimertinib.
Implications for Treatment
The MARIPOSA trial introduces amivantamab and lazertinib as a potential novel first-line treatment option for NSCLC patients with sensitizing EGFR mutations. This regimen may be particularly beneficial for younger, more fit patients who can tolerate the additional low-grade toxicities. The combination's efficacy in patients with CNS metastases is also a significant advantage. Furthermore, the chemotherapy-free nature of this combination may be preferable for patients in whom platinum-based chemotherapy is contraindicated or for those who prefer to reserve that option for later treatment stages.
Future Directions
While the MARIPOSA trial results are promising, further research is needed to identify which patients are most likely to benefit from this combination therapy. Identifying biomarkers that predict response and resistance mechanisms will be crucial for personalizing treatment strategies. Additionally, studies exploring the impact of this regimen on patient quality of life and healthcare resource utilization are warranted.
