Crizotinib in ROS1-Rearranged Non–Small-Cell Lung Cancer

This small, preliminary study of crizotinib in advanced ROS1-rearranged NSCLC reports an objective response rate of 72% (3 complete and 33 partial) and a median progression-free survival of 19.2 months (95% CI, 14.4 to not reached).

In the UK, crizotinib is licensed for the treatment of adults with previously treated anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC).

 

ROS1 (ROS1 proto-oncogene receptor tyrosine kinase) rearrangements occur in approximately 1% of patients with NSCLC. As with ALK rearrangements, ROS1 rearrangements are more commonly found in patients who have never smoked or have a history of light smoking and who have histologic features of adenocarcinoma. However, at the genetic level, ALK and ROS1 rearrangements rarely occur in the same tumour, with each defining a unique molecular subgroup of NSCLC.

 

There is evidence to suggest that ROS1 may represent another therapeutic target of crizotinib. The results of the current study suggest that it has potent antitumor activity in patients who had advanced NSCLC with a ROS1 rearrangement, and validate ROS1 as a therapeutic target in ROS1-rearranged lung cancers.