The FDA on Friday approved Xalkori (crizotinib) to treat patients with advanced non-small cell lung cancer (NSCLC) whose tumors have an ROS-1 gene alteration.
Xalkori, marketed by Pfizer, Inc., is the first and only FDA approved treatment for patients with ROS-1 positive NSCLC. It also is indicated for patients with metastatic NSCLC whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test.
Lung cancer is the leading cause of cancer-related deaths in the United States, with an estimated 221,200 new diagnoses and 158,040 deaths in 2015, according to the National Cancer Institute.
ROS-1 gene alterations, present in approximately 1 percent of patients with NSCLC and thought to lead to abnormal cells, have been identified in various cancers.
“Lung cancer is difficult to treat, in part, because patients have different mutations, some of which are rare,” Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said. “The expanded use of Xalkori will provide a valuable treatment option for patients with the rare and difficult to treat ROS-1 gene mutation by giving health care practitioners a more personalized way of targeting ROS-1 positive NSCLC.”
The oral medication blocks the activity of the ROS-1 protein in tumors that have ROS-1 gene alterations, an effect that may prevent NSCLC from growing and spreading.
Dr. Mace Rothenberg, chief medical officer for Pfizer Oncology, labeled the approval “an important milestone for patients who previously had limited treatment options.”
The current approval was based on a multicenter, single-arm trial that enrolled 50 patients ranging in age from 25 to 77 whose tumors were prospectively determined to be ROS1-positive by fluorescence in situ hybridization or reverse transcription polymerase chain reaction clinical trial assays.
Patients received Xalkori twice daily to measure the drug’s effect on their lung cancer tumors. The studies were designed to measure overall response rate, the percentage of patients who experienced complete or partial shrinkage of their tumors.
Results showed 66 percent of participants experienced a complete or partial shrinkage of their NSCLC tumors, an effect that lasted a median of 18.3 months.
“The approval of crizotinib for metastatic ROS1-positive non-small cell lung cancer represents another significant step forward in biomarker-driven cancer care,” Dr. Alice Shaw, principal study investigator, said. “As with ALK-positive lung cancer, ROS1-positive lung cancer defines a distinct subset of patients for whom crizotinib is efficacious.” Dr. Shaw serves as associate professor of medicine at Massachusetts General Hospital and Harvard Medical School.
An FDA-approved test for the detection of ROS1 rearrangements in NSCLC is not currently available. However, laboratory developed tests are obtainable. A companion diagnostic test is currently under development to identify patients with ROS1-positive metastatic NSCLC who may benefit from treatment with Xalkori.
(Sources: FDA, Pfizer, Inc., National Cancer Institute)