Updated progression-free survival and overall survival data from a multi-center European trial have confirmed earlier findings that the tyrosine kinase inhibitor crizotinib (Xalkori, Pfizer) is highly effective in patients with advanced or metastatic ROS1-rearranged non small-cell lung cancer (NSCLC), according to research presented at the American Society of Clinical Oncology Annual Meeting.

 The researchers -- led by principal investigator Juergen Wolf, MD of the University of Cologne in Cologne, Germany -- noted that ROS1 rearrangements are found in approximately 1% of all NSCLC patients. 

Lung cancer illustration. Source: Getty

Although early clinical trials have demonstrated the therapeutic efficacy of crizotinib in such patients in the US and Asia, the current phase II study -- EUCROSS (European Trial on Crizotinib in ROS1 Translocated Lung Cancer) -- is the first prospective trial to evaluate the activity of crizotinib in ROS1-positive lung cancer in a European population. 

“In individual treatment attempts and an ongoing phase I trial, crizotinib has shown remarkable effects on this selected subgroup of lung cancer patients,” the authors wrote. “Here we present an updated analysis of the investigator-assessed progression-free survival and overall survival.”

The trial included adult patients (≥18 years) with advanced/metastatic ROS1-rearranged lung centrally confirmed with fluorescence-in situ hybridization presenting at institutions in Germany, Spain, and Switzerland. The participants all received 250 mg twice-daily doses of crizotinib. Tumor response to treatment was assessed every six weeks by either CT or MRI scan. 

The study’s primary endpoint was investigator-assessed objective response rate in the response-evaluable population, as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. 

In total, 30 patients received treatment with crizotinib and were included in the primary endpoint analysis; their median follow-up was 44.9 months. At the data cut-off point, 63% (n = 19) had discontinued treatment due to progression or death. 

It was found that investigator-assessed objective response rate was 70% (n=21; 95% CI: 51-85). Disease control rate was found to be 90% (n=27; 95% CI: 73.5-97.9), while median progression-free survival was 19.4 months (95% CI: 10.1-31.2). 

Although median overall survival was not reached, 24-month overall survival probability was 66% (95% CI: 48.3-82.9%). 

Tissue samples were available from 18 patients for hybrid-capture-based sequencing. This analysis found that co-occurring genetic aberrations occurred in 61% of patients (11/18). Among these, TP53 mutations were most common, affecting five of the 18 patients (28%). 

Perhaps not surprisingly, both progression-free survival and overall survival were both significantly shorter in TP53-mutant patients. Specifically, 24-month probability progression-free survival was 0% among TP53-mutant patients, compared with 61% for patients with TP53 wild-type cancer (P = 0.0219). Similarly, 24-month overall survival was 40% among TP53-mutant patients and 83% for their counterparts with TP53 wild-type cancer (P = 0.015). 

Finally, differences in overall survival and progression-free survival -- when stratified by number of prior treatment lines (0-1 vs. ≥2), brain metastases (yes vs. no), and CD74-rearrangement status (CD74-ROS1 vs. other fusion type) -- were not significant.