Chemotherapy-Free Combination Approved by FDA for EGFR-Mutated NSCLC

By: JNCCN 360 Staff
Posted: Wednesday, August 21, 2024

The U.S. Food and Drug Administration (FDA) recently approved the bispecific antibody amivantamab-vmjw (Rybrevant) plus the EGFR tyrosine kinase inhibitor lazertinib (Lazcluze) in the first-line treatment of adults with locally advanced or metastatic non–small cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test.

This approval is based on the results of the phase III MARIPOSA trial of the combination therapy in this patient population. Amivantamab plus lazertinib reduced the risk of disease progression or death by 30% compared with osimertinib (23.7 months vs 16.6 months). The median duration of response, a secondary study endpoint, was 9 months longer with the combination vs osimertinib (25.8 months vs 16.7 months). Longer-term follow-up data from this trial will be presented at the upcoming International Association for the Study of Lung Cancer (IASLC) 2024 World Congress on Lung Cancer (WCLC) in September.

The most common adverse reactions (≥ 20%) were rash, nail toxicity, infusion-related reactions (with amivantamab), musculoskeletal pain, edema, stomatitis, venous thromboembolism (VTE), paresthesia, fatigue, diarrhea, constipation, COVID-19 infection, hemorrhage, dry skin, decreased appetite, pruritus, nausea, and ocular toxicity. A serious safety signal of VTE was observed with lazertinib in combination with amivantamab, and prophylactic anticoagulation should be administered for the first 4 months of therapy.

The recommended lazertinib dose is 240 mg orally once daily administered in combination with amivantamab with or without food. The recommended amivantamab dose is based on baseline body weight.

Earlier this year, the FDA approved the use of amivantamab in combination with chemotherapy (carboplatin-pemetrexed) in the first-line setting of patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations. This indication from March 2024 was based on the results of the phase III PAPILLON trial.

U.S. Food and Drug Administration

---