ASCO 2012 Report – Crizotinib shows promise in patients with advanced NSCLC with ROS1 rearrangements

by Marybeth Burke – Crizotinib demonstrated significant anti-tumour activity in patients with advanced non-small cell lung cancer (NSCLC) harbouring ROS1 rearrangements, according to a study released at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago in June.

“Crizotinib is a very potent inhibitor of ROS1.  This study validates for the first time that ROS1 is a therapeutic target in lung cancer,” according to Alice Tsang Shaw, MD, PhD, a thoracic oncologist at Massachusetts General Hospital Cancer Center, Boston, MA, who presented the data also published as Abstract 7508.

“Crizotinib demonstrates preliminary efficacy in this subtype of lung cancer.  I don’t think anyone can argue with this data,” added Gregory J. Riely, MD, PhD, an oncologist at Memorial-Sloan Kettering Cancer Center, NYC.

Role of ROS1 and Study Method

Chromosomal rearrangements of the ROS1 receptor tyrosine kinase gene define a new molecular subset of NSCLC.  Investigators sought to determine the efficacy and safety of crizotinib, a small molecule tyrosine kinase inhibitor of MET, ALK and ROS, in patients with advanced, ROS1-rearranged NSCLC, according to the abstract.

Investigators, utilizing a break-apart FISH assay, recruited patients with advanced NSCLC with ROS1 rearrangement into an expansion cohort of a Phase 1 study of crizotinib.  Patients were treated with crizotinib at the standard oral dose of 250mg BID.  The objective response rate (ORR) was determined based on RECIST 1.0.  The disease control rate (DCR) was measured at 8 weeks.

Results

Thirteen patients within the ROS expansion cohort received crizotinib and all were evaluable for response, according to the abstract.  Median age was 47 years and all but one of the patients were never smokers.  All patients had adenocarcinoma histology.  Twelve out of the 13 patients were tested for ALK rearrangement and were negative.  Median number of prior treatments was one (range 0 to 3).

“To date, the ORR is 54% (7/13), with 6 partial responders (PR) and 1 complete response, with 6 responses achieved by the first restaging scan at 7-8 weeks.  There was 1 additional unconfirmed PR at the time of data cut-off,” according to the abstract.

The DCR at 8 weeks was 85% (11/13).   Median duration of treatment was 20 weeks and all responses are ongoing and 12 patients continue on the study.  One patient had disease progression at first restaging and was discontinued from the study.

“Like ALK, ROS defines a distinct subpopulation of NSCLC patients for whom crizotinib therapy may be highly effective,” according to the abstract.

In addition, “Overall, crizotinib does appear to be extremely well tolerated in this population,” Dr Shaw said at the conference, noting that a few patients had relapsed and researchers need to devise strategies to overcome resistance.

Dr Riely observed that ROS1 positive lung cancer is fairly uncommon and found in just 1-2% of lung cancers and that it’s critical to have a good assay to identify patients with ROS1 positive lung cancer.

“We have a target.  We have a drug.  Now we need to find the patients.  We need to routinely identify these patients,” he said at the conference.