Dr Sabari on the FDA Approval of Amivantamab/Lazertinib in EGFR+ Advanced NSCLC

Joshua K. Sabari, MD, associate professor, Department of Medicine, New York University (NYU) Grossman School of Medicine, and medical director, Thoracic Medical Oncology, NYU Langone Health’s Perlmutter Cancer Center, discusses the FDA approval of amivantamab-vmjw (Rybrevant) plus lazertinib (Lazcluze) in EGFR-mutated advanced non–small cell lung cancer (NSCLC).

On August 20, 2024, the regulatory agency approved the combination for the first-line treatment for patients with locally advanced or metastatic NSCLC harboring EGFR exon 19 deletions or exon 21 L858R substitution mutations.

Data from the phase 3 MARIPOSA trial (NCT04487080)supported the FDA’s approval of the combination. Findings showed that at a median follow-up of 22.0 months, the median progression-free survival (PFS) was 23.7 months (95% CI, 19.1-27.7) for patients receiving the combination (n = 429) vs 16.6 months (95% CI, 14.8-18.5) for those receiving osimertinib (Tagrisso) alone (n = 429; HR, 0.70; 95% CI, 0.58-0.85; P < .001). Sabari notes that the 12-month PFS rates were 73% with the combination vs 65% with osimertinib alone. The 24-month PFS rates were 48% and 34%, respectively.

The median OS was not evaluable (NE) for both amivantamab plus lazertinib and osimertinib alone (HR, 0.80; 95% CI, 0.61-1.05). The 18- and 24-month OS rates for the combination were 82% (95% CI, 78%-85%) and 74% (95% CI, 69%-78%), respectively. In the osimertinib arm, those respective rates were 79% (95% CI, 75%-83%) and 69% (95% CI, 64%-74%).

Sabari says that these findings were consistent with clinical observations for osimertinib, where approximately half of patients experience disease progression within 2 years of beginning first-line treatment. He notes that the combination of amivantamab and lazertinib offers a new therapeutic approach to extend PFS compared with the current standard of care.

Sabari concludes that the deeper and more sustained responses seen with this regimen could translate into meaningful clinical benefit, offering patients a longer duration of disease control and potentially improving quality of life.