August 2024: The Food and Drug Administration (FDA) has granted approval for the use of lazertinib (Lazcluze, Janssen Biotech, Inc.) in combination with amivantamab-vmjw (Rybrevant, Janssen Biotech, Inc.) as the initial treatment for non-small cell lung cancer (NSCLC) that is locally advanced or has spread to other parts of the body.
This treatment is specifically intended for patients with NSCLC who have specific genetic mutations known as epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations. These mutations can be identified through a test that has been approved by the FDA.
Safety and efficacy
The efficacy of the treatment was assessed in a clinical trial called MARIPOSA (NCT04487080). This clinical trial had 1074 patients who had locally advanced or metastatic non-small cell lung cancer (NSCLC) with a specific genetic mutation (exon 19 deletion or exon 21 L858R replacement). These patients had not received any previous systemic therapy for their advanced disease.
The trial was randomized and included many centers. The patients were randomly assigned in a ratio of 2:2:1 to receive either a combination of lazertinib and amivantamab, osimertinib alone, or lazertinib alone (which is not an approved treatment for NSCLC). They continued with their assigned treatment until their disease progressed or they experienced intolerable levels of toxicity.
The primary measure of effectiveness was the length of time without disease progression (progression-free survival or PFS). This was evaluated by an impartial review board (blinded independent central review or BICR) to compare the effectiveness of lazertinib with amivantamab and osimertinib. The overall survival (OS) was a significant secondary outcome measure. The combination of lazertinib and amivantamab showed a substantial improvement in progression-free survival (PFS) compared to osimertinib.
The hazard ratio was 0.70 (95% confidence interval [CI]: 0.58, 0.85; p-value=0.0002). In the lazertinib with amivantamab arm, the median progression-free survival (PFS) was 23.7 months (95% CI: 19.1, 27.7), while in the osimertinib arm, it was 16.6 months (95% CI: 14.8, 18.5).
Although the OS results were not fully developed in the current analysis, with only 55% of the pre-specified fatalities reported for the final analysis, there was no indication of a negative trend.
The predominant adverse effects (≥20%) observed were rash, nail toxicity, infusion-related reactions (specifically with amivantamab), musculoskeletal pain, edema, stomatitis, venous thromboembolism, paresthesia, fatigue, diarrhea, constipation, COVID-19 infection, hemorrhage, dry skin, decreased appetite, pruritus, nausea, and ocular toxicity.
Lazertinib, when used in conjunction with amivantamab, has shown a significant risk of venous thromboembolic events (VTE). Therefore, it is recommended to administer preventive anticoagulation during the initial four months of therapy.
The suggested dosage for lazertinib is 240 mg taken orally once a day, either with or without food, in conjunction with amivantamab. The prescribed dosage of amivantamab is determined by the individual’s initial body weight. Refer to the prescribed instructions for precise details on dosage.
