Lazertinib Plus Amivantamab Receives FDA Approval for Lung Cancer

On 19 August 2024, the FDA (US Food and Drug Administration) granted first-line treatment approval for patients with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations and locally advanced or metastatic non-small cell lung cancer (NSCLC), using a combination of lazertinib (Lazcluze, Janssen Biotech, Inc.) and amivantamab-vmjw (Rybrevant, Janssen Biotech, Inc.). The approval applies to mutations detected by an FDA-approved test.

FDA Approval Based on MARIPOSA

The combination’s effectiveness was evaluated in MARIPOSA, a randomized, active-controlled, multicenter study. It included 1074 patients with EGFR exon 19 deletion- or exon 21 L858R mutation-positive locally advanced or metastatic NSCLC who had received no prior systemic therapy for advanced disease.

Patients were randomized in a 2:2:1 ratio to lazertinib plus amivantamab, osimertinib monotherapy, or lazertinib monotherapy (a regimen not yet approved for NSCLC).

Results

The main efficacy outcome was progression-free survival (PFS) assessed by blinded independent central review.

• Lazertinib plus amivantamab significantly improved PFS compared with osimertinib alone (hazard ratio 0.70; 95% confidence interval [CI]: 0.58, 0.85; p=0.0002).
• Median PFS in patients receiving lazertinib plus amivantamab was 23.7 months (95% CI: 19.1, 27.7), compared with 16.6 months (95% CI: 14.8, 18.5) in patients receiving osimertinib.

Overall survival (OS) results remain immature, with 55% of the deaths planned for the final analysis having occurred. However, no unfavorable trend was observed in the available data.

The most common adverse effects (≥20%) were rash, nail toxicity, infusion-related reactions (amivantamab), musculoskeletal pain, edema, stomatitis, venous thromboembolism, paresthesia, fatigue, diarrhea, constipation, COVID-19 infection, bleeding, dry skin, loss of appetite, pruritus, nausea, and ocular toxicity. A serious safety signal involving venous thromboembolic events (VTE) was observed with lazertinib plus amivantamab, and prophylactic anticoagulation is recommended during the first four months of treatment.

The recommended lazertinib dose is 240 mg orally once daily, with or without food. The recommended amivantamab dose is based on initial body weight. Consult the prescribing information for specific dosing details.

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Comparative Analysis: Existing Approved Treatments

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FLAURA 2 and FDA Approval

On 16 February 2024, the FDA approved osimertinib with platinum-based chemotherapy as first-line treatment for locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations. This approval was based on FLAURA 2, which showed a significant PFS improvement over osimertinib monotherapy. Median PFS with the combination was 25.5 months, compared with 16.7 months with osimertinib monotherapy.

MARIPOSA and FDA Approval

MARIPOSA showed that lazertinib plus amivantamab significantly improved PFS compared with osimertinib monotherapy. Median PFS was 23.7 months with lazertinib plus amivantamab and 16.6 months with osimertinib.

Comparative Assessment

Both studies offer effective options for patients with EGFR-mutated advanced NSCLC. While osimertinib plus chemotherapy in FLAURA 2 provided the best disease-free survival value, MARIPOSA showed that lazertinib plus amivantamab could be an effective alternative.

Both regimens had certain adverse effects. However, the higher rate of serious events such as venous thromboembolism (VTE) reported with lazertinib plus amivantamab in MARIPOSA requires careful treatment management.

Both regimens offer promising options for EGFR-mutated NSCLC, but treatment must be selected carefully according to individual circumstances and safety profiles.