Dr. Velcheti on Potential of Alectinib in Frontline ALK-Positive NSCLC

Vamsidhar Velcheti, MD, an assistant professor of Medicine at Cleveland Clinic Lerner School of Medicine, discusses the ALK inhibitor alectinib and what potential the agent could have in the frontline setting for patients with ALK-positive non—small cell lung cancer (NSCLC). Velcheti shared this insight in an interview during the 2016 OncLive State of the Science Summit on Non—Small Cell Lung Cancer.

An exciting clinical trial in this space is the Japanese J-ALEX study of alectinib, which is a newer generation and more potent ALK inhibitor in the first-line setting in patients who have metastatic lung cancer and ALK fusion, Velcheti explains. This study compared against the standard of care crizotinib (Xalkori) in patients who were previously untreated.

Results of the study showed that there was a significant increase in progression-free survival (PFS) of 66%, as well as a hazard ratio of .34. Velcheti adds that this is an incredible advance in treating patients with ALK-positive lung cancers. This demonstrates that use of more potent ALK inhibitors in the frontline setting offers a better progression-free control and could have a significant clinical benefit.

In October 2016, the FDA granted alectinib a breakthrough therapy designation as a frontline treatment for patients with ALK-positive NSCLC, based on the J-ALEX findings. The trial randomized 207 Japanese patients with ALK-positive advanced or recurrent NSCLC who had not previously received an ALK inhibitor to alectinib at 300 mg twice daily, or crizotinib at 250 mg twice daily. Patients continued treatment until disease progression or unacceptable toxicity.

The median PFS was not reached (95% CI, 20.3—not estimated) in the alectinib arm compared with 10.2 months (95% CI, 8.2-12) in the crizotinib cohort (HR, 0.34; 99% CI, 0.17-0.70; P <.0001). In a subgroup of patients with brain metastases at baseline, the hazard ratio for PFS with alectinib versus crizotinib was .08 (95% CI, 0.01-0.61).

The investigator-assessed objective response rates (ORRs) were 85.4% in the alectinib group and 70.2% in the crizotinib arm. By the independent review, the ORR was 91.6% in alectinib cohort.