The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for Pfizer Inc's Xalkori for the potential treatment of patients with ROS1-positive non-small cell lung cancer (NSCLC). Occurring in approximately one percent of NSCLC cases, ROS1-positive NSCLC represents a particular molecular subgroup of NSCLC.

Xalkori, a kinase inhibitor currently indicated in the US for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test. Xalkori has received approval in more than 80 countries10 including Australia, Canada, China, Japan, South Korea and the European Union.

Enacted as part of the 2012 FDA Safety and Innovation Act (FDASIA), breakthrough therapy designation is intended to expedite the development and review of a potential new medicine if it is “intended to treat a serious or life-threatening disease and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies.

The breakthrough therapy designation is distinct from the FDA’s other mechanisms to expedite drug development and review.

“We are excited that the FDA has granted breakthrough therapy designation for Xalkori as a potential treatment for patients with ROS1-positive NSCLC,” said Dr. Mace Rothenberg, senior vice president of Clinical Development and Medical Affairs and chief medical officer for Pfizer Oncology.

“Xalkori pioneered precision medicine for ALK-positive metastatic NSCLC, and ROS1 represents a second molecular subgroup of NSCLC in which Xalkor has demonstrated a level of anti-tumor activity that can potentially make a real difference for patients.”

Pfizer will work closely with the FDA on the development of Xalkori for ROS1-positive NSCLC and provide the information needed to support a potential regulatory submission.

The breakthrough therapy designation was based on a data analysis from an expansion cohort of a global phase 1 study (study 1001), which evaluated Xalkori in 50 patients with ROS1-positive advanced NSCLC.

These data published in the November 20, 2014 issue of the New England Journal of Medicine demonstrated that Xalkori exhibited marked anti-tumor activity in patients with ROS1-positive advanced NSCLC.

The safety profile of Xalkori in ROS1-rearranged advanced NSCLC was similar to that observed in patients with ALK-positive advanced NSCLC.

The most common events with crizotinib were visual impairment (82%), diarrhea (44%), nausea (40%), peripheral edema (40%), constipation (34%), vomiting (34%), an elevated aspartate aminotransferase level (22%), fatigue (20%), dysgeusia (18%), and dizziness (16%).

The most common grade 3 adverse events were hypophosphatemia (10%), neutropenia (10%), and an elevated alanine aminotransferase level (4%). Additionally, one patient (2%) discontinued crizotinib because of treatment-related nausea.

Lung cancer is the leading cause of cancer death worldwide. NSCLC accounts for about 85 percent of lung cancer cases and remains difficult to treat, particularly in the metastatic setting. Approximately 75 percent of NSCLC patients are diagnosed late with metastatic, or advanced, disease where the five-year survival rate is only 5 percent.