Amivantamab-Lazertinib Boosts Survival in EGFR-Mutated Lung Cancer

A recent study has shown promising results for patients with EGFR-mutated advanced non-small cell lung cancer (NSCLC) using the combination treatment of amivantamab-lazertinib. This combination has demonstrated improved progression-free survival outcomes compared to osimertinib when used as a first-line treatment. Published online on June 26 in the New England Journal of Medicine, the study by Dr. Byoung C. Cho and colleagues from the Yonsei Cancer Center in Seoul, South Korea, presents pivotal findings in the treatment landscape for this type of lung cancer.

The research team conducted a phase 3 clinical trial involving patients who had not previously received treatment for their EGFR-mutated, locally advanced, or metastatic NSCLC. Participants were randomly assigned to receive either amivantamab-lazertinib (open-label), osimertinib (blinded), or lazertinib (blinded) in a 2:2:1 ratio. The study included a total of 1,074 patients, with 429 patients each in the amivantamab-lazertinib and osimertinib groups and 216 patients in the lazertinib group.

The results revealed that the median progression-free survival was significantly longer for patients in the amivantamab-lazertinib group compared to those in the osimertinib group, with durations of 23.7 months versus 16.6 months, respectively. This was reflected in a hazard ratio of 0.70 for disease progression or death, indicating a substantial reduction in the risk for patients receiving the combination treatment.

Additionally, the study observed high objective response rates in both treatment groups, with 86 percent in the amivantamab-lazertinib group and 85 percent in the osimertinib group. Among patients who had a confirmed response, the median duration of response was 25.8 months for the combination therapy group, compared to 16.8 months for the osimertinib group.

However, the planned interim overall survival analysis did not show a significant difference in the hazard ratio for death between the two treatments, suggesting that further follow-up may be necessary to determine any long-term survival benefits.

In terms of safety, EGFR-related toxic effects were the most common adverse events reported. The incidence of treatment-related adverse event discontinuations was higher in the amivantamab-lazertinib group at 10 percent, compared to 3 percent in the osimertinib group. This indicates that while the combination therapy may offer better progression-free survival, it also comes with a higher likelihood of adverse events leading to treatment discontinuation.

The authors concluded that the combination of amivantamab-lazertinib offers a significant improvement in progression-free survival compared to osimertinib as a first-line treatment for patients with EGFR-mutated advanced NSCLC. They highlighted the importance of these findings in potentially guiding future treatment strategies for this patient population.

It is worth noting that the study was funded by Janssen, the manufacturer of amivantamab and lazertinib, and several authors disclosed affiliations with various biopharmaceutical companies, including Janssen.