Amivantamab-vmjw Plus Chemotherapy Approved for Non–Small Cell Lung Cancer With EGFR Exon 19 Deletions or L858R Mutations
Expert Perspectives · Lyn Brook · 2024-09-20
The FDA has granted approval to amivantamab-vmjw (Rybrevant®, Janssen Biotech, Inc.) plus carboplatin and pemetrexed for adult patients with 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 whose disease has progressed on or after treatment with an EGFR tyrosine kinase inhibitor.
Why it matters: “Amivantamab plus carboplatin and pemetrexed (chemotherapy) with and without lazertinib demonstrated antitumor activity in patients with refractory EGFR-mutated advanced NSCLC in phase 1 studies,” wrote Antonio Passaro, MD, PhD, a Medical Oncologist in the Division of Thoracic Oncology at the European Institute of Oncology, and colleagues, in their published results of the MARIPOSA-2 trial (NCT04988295), on which approval was based.
What they studied: Efficacy was measured in the phase 3, open-label, multicenter trial which enrolled 657 patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations and disease progression on or after receiving osimertinib. Patients were randomized 1:2:2 to receive either amivantamab-vmjw plus carboplatin and pemetrexed, carboplatin and pemetrexed, or amivantamab-vmjw as part of another combination regimen.
The primary efficacy outcome measured, comparing amivantamab-vmjw plus carboplatin and pemetrexed versus carboplatin and pemetrexed alone, was progression-free survival as assessed by Blinded Independent Central Review (BICR). Two key secondary efficacy outcomes were measured as well: overall response rate as assessed by BICR and overall survival.
What they found:
- Progression-free survival was a median of 6.3 months in the amivantamab-vmjw arm compared with 4.2 months in the carboplatin and pemetrexed alone arm
- Overall response rate was 53% in the amivantamab-vmjw arm compared with 29% in the carboplatin and pemetrexed alone arm
- Overall survival, at the point of the prespecified second interim analysis and 85% of the deaths required for the final analysis, saw no statistically significant difference between the two arms and had a hazard ratio of 0.73
Adverse events: The most common adverse events experienced in ≥20% of patients receiving amivantamab-vmjw were rash, infusion-related reactions, fatigue, nail toxicity, nausea, constipation, edema, stomatitis, decreased appetite, musculoskeletal pain, vomiting, and COVID-19 infection.
Conclusion: “Amivantamab plus chemotherapy and amivantamab plus lazertinib and chemotherapy improved progression-free survival and intracranial progression-free survival versus chemotherapy in a population with limited options after disease progression on osimertinib,” concluded Dr. Passaro and colleagues. “Longer follow-up is needed for the modified amivantamab-lazertinib-chemotherapy regimen.”
Instructions: The recommended dosage of amivantamab-vmjw is based on baseline body weight. Refer to the prescribing information for specific dosage information.