Crizotinib treatment has been revealed to be effective against ROS1-positive lung cancer, according to a study published in the New England Journal of Medicine. The research team presented their work at the European Society for Medical Oncology (ESMO) meeting, reporting that crizotinib treatment lead to a meaningful tumor shrinkage in 36 of 50 participants and suppressed tumor growth in 9 other participants.
Crizotinib is an FDA-approved drug to treat patients with non-small-cell lung cancers (NSCLC) caused by rearrangements in the ALK gene (about 4% of the cases).
Alice Shaw, MD, PhD, first author of the publication, affiliated with the Massachusetts General Hospital (MGH) Cancer Center explained in a MGH’s press release that several reports describe crizotinib interactions with ROS1-positive lung tumors yet “this is the first definitive study to establish crizotinib’s activity in a large group of patients with ROS1-positive lung cancer and to confirm that ROS1 is a bona fide therapeutic target in those patients.”
In another MGH study from 2012, published in the Journal of Clinical Oncology , it was reported that 1 to 2% of all NSCLCs are actually driven by rearrangements in the ROS1 gene. “ROS1 encodes a protein [structural similar to the one encoded by the ALK gene] that is important for cell growth and survival, and deregulation of ROS1 through chromosomal rearrangement drives the growth of tumors,” Dr. Shaw stated in the 2012 MGH press release.
This study enrolled 50 patients with ROS1-positive NSCLC, who received 2 daily doses of crizotinib. In 18% of patients tumor growth was ceased while 72% saw their tumor sizesignificantly reduced; the response to the treatment had an average duration of 17 months. Importantly, 25 of the 50 patients participating in the study continued receiving crizotinib and showed no evidences of tumor progression.
After a continuous repetition of the treatment, a common procedure in other targeted cancer therapies, patients developed resistance to the treatment. Nevertheless, the effectiveness of this drug lasted longer in ROS1-positive cancers than in ALK-positive ones. “Fortunately, the remissions induced by crizotinib in ROS1-positive patients are quite prolonged, and resistance appears to emerge much later, on average, than what we have seen with other targeted therapies for lung cancer and melanoma,” Dr. Shaw added in the press release.
Crizotinib’s treatment is approved by the FDA to be administered in ALK-positive NSCLC but, given the recent discoveries, the National Comprehensive Cancer Network recommend patients suffering with advanced lung cancer to be tested and considered for crizotinib treatment if they have ROS1-positive cancer.
The study was funded by Pfizer, the pharmaceutical company holding crizotinib in the market under the brand name Xalkori, the National Cancer Institute, Uniting Against Lung Cancer and Be a Piece of the Solution.
