MARIPOSA in First-Line EGFRm Non–Small Cell Lung Cancer: Patient Selection and Emerging Survival Data

Summary of MARIPOSA Frontline Treatment and Patient Selection Considerations

The MARIPOSA regimen, combining amivantamab plus lazertinib, has emerged as a significant frontline treatment option for patients with common EGFR mutations (exon 19 deletions and L858R). This combination demonstrates efficacy roughly equivalent to that of osimertinib monotherapy, with slight differences in adverse effect profiles including potentially less cardiac toxicity and different pneumonitis risk patterns. The regimen works through dual targeting: lazertinib functions as an EGFR tyrosine kinase inhibitor similar to osimertinib, while amivantamab serves as an EGFR/MET bispecific antibody that targets extracellular EGFR and helps overcome early acquired resistance driven by MET amplification.

Recent press release data suggests MARIPOSA may provide approximately 12 months of overall survival benefit compared with osimertinib monotherapy, representing a potentially practice-changing development since FLAURA2 has not yet demonstrated proven overall survival benefits. However, the regimen introduces additional toxicities including EGFR-related adverse effects (rash, diarrhea) and MET inhibitor–associated lower extremity edema, with most adverse effects occurring within the first 4 months. The treatment also presents psychosocial considerations due to visible facial rash development and currently requires prolonged intravenous infusions with associated venous thromboembolism (VTE) risk requiring anticoagulation prophylaxis, though a subcutaneous formulation in development may address these concerns.

Patient selection for frontline regimens remains complex and individualized rather than driven by single factors. While specific tumor characteristics like MET amplification (present in less than 5% of cases) might favor MARIPOSA, the demonstrated overall survival benefit may increase its utilization regardless of patient-specific factors. For FLAURA2 consideration, important factors include baseline circulating tumor DNA presence and clearance patterns, with nonclearance suggesting faster resistance development, as well as high-risk features like central nervous system metastases where combination therapy shows particular benefit with hazard ratios below 0.5. The decision-making process requires balancing multiple tumor and host factors rather than relying on single predictive markers.