On August 19, 2024, the U.S. Food and Drug Administration (FDA) approved the combination therapy of lazertinib (Lazcluze) and amivantamab-vmjw (Rybrevant) for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC), and the FDA-approved test with EGFR exon 19 deletion or deletion. Mutation in the exon 21 L858R gene.
MARIPOSA Research
The efficacy of this therapy was evaluated in the MARIPOSA study (Clinical Trial No. NCT04487080). This was a randomized, active-controlled, multicenter trial that enrolled 1,074 patients with locally advanced or metastatic NSCLC who had EGFR exon 19 deletion or exon 21 L858R mutation and had not previously received any systemic therapy. Patients were randomized to three groups in a 2:2:1 ratio: lazertinib and amivantamab combination group, osimertinib monotherapy group, and lazertinib monotherapy group (this therapy is not approved for NSCLC). Treatment continued until disease progression or unacceptable toxicity occurred.
The primary efficacy endpoint was progression-free survival (PFS) in a blinded, independently reviewed, centrally assessed study, comparing the lazertinib and amivantamab combination group with the osimertinib group; overall survival was a key secondary endpoint. The lazertinib and amivantamab combination group demonstrated statistically significant superiority over osimertinib in PFS, with a hazard ratio of 0.70 (95% CI = 0.58–0.85, P = 0.0002). The median PFS in the lazertinib and amivantamab combination group was 23.7 months (95% CI = 19.1–27.7 months), compared to 16.6 months (95% CI = 14.8–18.5 months) in the osimertinib group. Although overall survival results were not mature at the time of this analysis (with only 55% of the pre-specified deaths), no adverse trend was observed.
The most common adverse reactions (incidence ≥20%) include rash, nail toxicity, infusion-related reactions (related to amivantamab), musculoskeletal pain, edema, oral mucositis, venous thromboembolism, paresthesia, fatigue, diarrhea, constipation, COVID-19 infection, bleeding, dry skin, decreased appetite, pruritus, nausea, and ocular toxicity. Safety signals for venous thromboembolic events have been observed with the combined use of lazertinib and amivantamab; prophylactic anticoagulation therapy should be initiated during the first 4 months of treatment.
The recommended dose of lazertinib is 240 mg orally daily, used in combination with amivantamab, with or without food. The recommended dose of amivantamab is determined based on baseline body weight.
Dr. Li Yu Chung, Jacky, a specialist in clinical oncology, believes that the new combination therapy can provide a new treatment option for EGFR-mutant lung cancer and improve disease control time. Furthermore, it provides a good research data basis for adding Amivantamb as a further treatment regimen when the initial efficacy of single oral targeted therapy is poor or when drug resistance develops.
