Lazertinib Plus Amivantamab-vmjw Approved for Non–Small Cell Lung Cancer
Expert Perspectives · Lyn Brook · 2024-08-22
The FDA has approved lazertinib (Lazcluze™, Janssen Biotech, Inc.) plus amivantamab-vmjw (Rybrevant®, Janssen Biotech, Inc.) for the first-line treatment of locally advanced or metastatic non–small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test.
Why it matters: “Third-generation EGFR tyrosine kinase inhibitors (TKIs), such as osimertinib, have demonstrated efficacy in patients with EGFR-mutant NSCLC; however, almost all patients will eventually relapse,” wrote Byoung Chul Cho, MD, Professor in the Division of Medical Oncology at Yonsei Cancer Center, and colleagues, in their published results of the MARIPOSA trial (NCT04487080), on which approval was based. “Amivantamab is an EGFR-MET bispecific antibody with immune cell–directing activity that targets activating and resistance EGFR mutations and MET mutations and amplifications.”
What they studied: Efficacy was measured in the phase 3, active-controlled, multicenter trial which enrolled 1,074 patients with exon 19 deletion or exon 21 L858R substitution mutation-positive locally advanced or metastatic NSCLC and no prior systemic therapy for advanced disease. Patients were randomized 2:2:1 to receive either lazertinib plus amivantamab, osimertinib monotherapy, or lazertinib monotherapy—an unapproved regimen for NSCLC—until disease progression or unacceptable toxicity.
The primary efficacy outcome measured was progression-free survival as assessed by Blinded Independent Central Review. The efficacy outcome compared lazertinib plus amivantamab and osimertinib. A key secondary efficacy outcome measured was overall survival.
What they found: Progression-free survival saw a statistically significant improvement in the lazertinib plus amivantamab arm compared with osimertinib, with a hazard ratio of 0.70. Median progression-free survival was 23.7 months with lazertinib plus amivantamab compared with 16.6 months with osimertinib. Overall survival results were immature at the time of analysis, with 55% of prespecified deaths for the final analysis reported, but no trend towards detriment was observed.
Adverse events: The most common adverse events experienced in ≥20% of patients receiving lazertinib were rash, nail toxicity, infusion-related reactions (amivantamab), musculoskeletal pain, edema, stomatitis, venous thromboembolism, paresthesia, fatigue, diarrhea, constipation, COVID-19 infection, hemorrhage, dry skin, decreased appetite, pruritus, nausea, and ocular toxicity. A serious safety signal of venous thromboembolic events (VTE) was observed with lazertinib plus amivantamab and prophylactic anticoagulation should be administered for the first four months of therapy.
Conclusion: “Amivantamab plus lazertinib was statistically superior to osimertinib, providing clinically meaningful improvement in progression-free survival, with higher duration of response and a favorable overall survival trend,” concluded Dr. Cho and colleagues. “The safety profile of amivantamab plus lazertinib was consistent with prior reports. MARIPOSA establishes amivantamab plus lazertinib as a new first-line standard of care for EGFR-mutated advanced NSCLC.”
Instructions: The recommended dosage is 240 mg of lazertinib orally, once daily, plus amivantamab, with or without food. The recommended dosage of amivantamab is based on baseline body weight. See the prescribing information for specific dosing information.
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