FDA approves first-line combination for EGFR-mutant non-small cell lung cancer
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The FDA approved amivantamab-vmjw plus lazertinib as first-line treatment for certain adults with non-small cell lung cancer.
The indication applies to use of the combination by patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations.
Amivantamab (Rybrevant, Janssen) is an EGFR-MET bispecific antibody. Lazertinib (Leclaza; Yuhan, Janssen) is a central nervous system-penetrant EGFR TKI.
The FDA based approval on results of the randomized phase 3 MARIPOSA trial, which included 1,074 patients (median age, 63 years; 62% women; 59% Asian).
Researchers randomly assigned 429 patients to amivantamab-lazertinib and 216 patients to lazertinib monotherapy. The other 429 patients received osimertinib (Tagrisso, AstraZeneca) — a third-generation EGFR tyrosine kinase inhibitor that serves as current standard first-line treatment for this population.
Baseline characteristics were balanced across treatment groups.
PFS by blinded independent central review served as the primary endpoint. Secondary endpoints included OS, objective response rate, duration of response, safety and PFS after first subsequent therapy.
As Healio previously reported, the combination conferred a 30% reduction in risk for disease progression or death compared with osimertinib (median PFS, 23.7 months vs. 16.6 months; HR = 0.7; 95% CI, 0.58-0.85).
The combination improved PFS regardless of brain metastases history (with history, HR = 0.69; 95% CI, 0.53-0.92; no history, HR = 0.69; 95% CI, 0.53-0.89), and it also improved extracranial PFS (median, 27.5 months vs. 18.5 months; HR = 0.68; 95% CI, 0.56-0.83).
Researchers reported comparable ORRs between the combination and osimertinib monotherapy groups (86% vs. 85%); however, results showed longer median duration of response among confirmed responders in the combination group (25.8 months vs. 16.8 months).
Interim OS analysis showed a trend toward improved survival with the combination, although the difference did not reach statistical significance (HR = 0.8; 95% CI, 0.61-1.05). At 24 months, 74% of patients assigned the combination and 69% of those assigned osimertinib remained alive.
A higher percentage of patients assigned the combination experienced grade 3 or higher treatment-emergent adverse events (75% vs. 43%) or serious events (49% vs. 33%). Thirty-four patients (8%) assigned the combination and 31 (7%) assigned osimertinib monotherapy died due to adverse events.
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