Dr. Levy on the Efficacy of Crizotinib Versus Entrectinib in ROS1+ Lung Cancer

Benjamin P. Levy, MD, associate professor of oncology and clinical director of Medical Oncology at Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital, discusses the efficacy of crizotinib (Xalkori) versus entrectinib (Rozlytrek) in ROS1-rearranged lung cancer.

One of the first points made in Levy’s presentation during the 21st Annual International Lung Cancer Congress® is to consider next-generation sequencing for both DNA and RNA in order to identify fusions such as ROS1. This is important because if these fusions cannot be identified, then targeted therapy cannot be delivered to these patients, says Levy.

Over the past 6 to 7 years, new drugs have become available that target ROS1 rearrangements in patients with lung cancer. The first drug is crizotinib; data published by Alice T. Shaw, MD, PhD, of Massachusetts General Hospital, showed a response rate of 72% with a median progression-free survival (PFS) of 19.2 months, says Levy. Because of these data, crizotinib was approved by the FDA for use as a targeted therapy in patients with metastatic NSCLC whose tumors are ROS1 positive.

More recently, entrectinib also received regulatory approval, adds Levy. The decision was based on data from an integrated analysis of the phase 2 STARTRK-2, phase 1 STARTRK-1, and phase 1 ALKA-372-001 trials, which looked specifically at 53 patients with ROS1 rearrangement who were treated with entrectinib. All patients were ROS1 inhibitor–naïve and had a response rate of 78% and a median PFS that was nearly identical to that of crizotinib, at 19.3 months, according to Levy. The difference with entrectinib was that it did show intracranial responses. Entrectinib is more potent than crizotinib, says Levy, having been designed to specifically cross the blood-brain barrier. As such, entrectinib induced an impressive intracranial response that had not been reported with crizotinib, concludes Levy.