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In a recent phase I trial by Shaw and colleagues, crizotinib demonstrated marked antitumor activity in patients with advanced ROS1-mutated non–small-cell lung cancer (NEJM JW Oncol Hematol Oct 7 2014 and N Engl J Med 2014; 371:1963).
To further evaluate the effectiveness of crizotinib in this setting, European investigators conducted an industry-supported, retrospective, international study (EUROS1), involving 29 evaluable patients (median age, 50.5 years; 65% women; 71% never smokers) with stage IV lung adenocarcinoma and ROS1 rearrangement. All tumors were adenocarcinomas, including five with lepidic components and one with adenosquamous histology. One patient was treatment naive, 9 had one prior therapy, and 21 had multiple prior therapies.
The overall response rate was 80%, and the disease control rate was 87%. Median progression-free survival (PFS) was 9.1 months, and the 1-year PFS rate was 44%. No grade 4 or 5 toxicities occurred; one patient experienced grade 3 liver enzyme elevation. Primary resistance to crizotinib occurred in the one patient with both KRAS mutation and ROS1 rearrangement.
Mazieres J et al. Crizotinib therapy for advanced lung adenocarcinoma and a ROS1 rearrangement: Results from the EUROS1 cohort. J Clin Oncol 2015 Mar 20; 33:992. (http://dx.doi.org/10.1200/JCO.2014.58.3302)
Solomon B.Validating ROS1 rearrangements as a therapeutic target in non–small-cell lung cancer. J Clin Oncol 2015 Mar 20; 33:972. (http://dx.doi.org/10.1200/JCO.2014.59.8334)
Comment
This trial confirms the results of the recent phase I trial by Shaw, in which patients with ROS1 rearrangement had a significant response to crizotinib therapy with minimal toxicity. There were two additional features of note in the current study. The first was the identification of primary resistance in a patient with dual KRAS and ROS1 mutation, and the second was the high incidence of adenocarcinoma with lepidic pattern associated with ROS1 rearrangement. However, because this trial included a small number of patients, additional information is needed to validate these observations.