Amivantamab Plus Chemotherapy Receives FDA Approval for Second-Line Treatment of EGFR-Mutant Lung Cancer

The FDA has approved treatment for non-small cell lung cancer (NSCLC) with EGFR exon 19 deletions or L858R mutations after previous anti-EGFR therapy: amivantamab-vmjw in combination with carboplatin and pemetrexed.

On September 19, 2024, the United States Food and Drug Administration (FDA) approved a combination treatment for patients with advanced or metastatic NSCLC involving amivantamab-vmjw (Rybrevant, Janssen Biotech, Inc.). This is considered a major development, particularly for patients with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations. The decision offers a new treatment option, particularly for patients whose disease progressed after previous EGFR tyrosine kinase inhibitor therapy.

FDA Approval Based on MARIPOSA-2

Amivantamab's efficacy was evaluated in MARIPOSA-2, a randomized, open-label, multicenter trial. The trial enrolled patients with EGFR exon 19 deletions or exon 21 L858R mutations who had previously received osimertinib, with 657 patients participating.

Patients were randomized to amivantamab with carboplatin and pemetrexed (amivantamab + CP), carboplatin and pemetrexed alone (CP), or another amivantamab combination regimen.

The primary efficacy endpoint for the comparison of amivantamab + CP with CP, assessed by blinded independent central review, was progression-free survival (PFS). Overall response rate and overall survival were important secondary endpoints.

Results

• Median progression-free survival was 6.3 months (95% CI: 5.6, 8.4) in the amivantamab + CP arm and 4.2 months (95% CI: 4.0, 4.4) in the CP arm (hazard ratio 0.48 [95% CI: 0.36, 0.64], p-value<0.0001).
• The confirmed objective response rate was 53% (95% CI: 44, 62) in the amivantamab + CP arm and 29% (95% CI: 23, 35) in the CP arm (p-value<0.0001).
• At the planned second interim analysis of overall survival, when 85% of the deaths required for the final analysis had occurred, there was no statistically significant difference in overall survival. The strategic overall survival hazard ratio was calculated as 0.73 (95% CI: 0.54, 0.99).

Common Side Effects

The most common side effects (20% or more) included rash, infusion-related reactions, fatigue, nail toxicity, nausea, constipation, edema, stomatitis, decreased appetite, musculoskeletal pain, vomiting and COVID-19 infection.

Conclusion

This new FDA approval offers an important treatment advance for patients with advanced or metastatic NSCLC who have previously received anti-EGFR therapy. Developed specifically for patients with EGFR mutations, this combination treatment has the potential to delay disease progression and improve quality of life. However, careful attention to treatment side effects is required.

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