European Results Confirm Crizotinib Active Against ROS1-Rearranged Lung Adenocarcinoma

A European cohort study points to crizotinib efficacy in advanced ROS1-positive lung adenocarcinoma

medwireNews: Results from the European Study of ROS1 Patients (EUROS1) indicate that the Tyrosine kinase inhibitor (TKI) crizotinib is efficacious in patients with stage IV lung adenocarcinoma with ROS1 Rearrangement.

Analysis of medical records from France, Switzerland, Italy, Germany, Poland and the Netherlands identified 31 such patients with FISH-confirmed ROS1 rearrangement who were given crizotinib 250 mg twice daily and underwent computed tomography imaging before and 6 to 8 weeks after beginning treatment.

The cohort study, conducted in the absence of a prospective clinical trial in Europe, gave a median progression-free survival (PFS) of 9.1 months for off-label crizotinib use and a PFS rate of 44% at 1 year.

Objective responses to crizotinib were noted for 24 patients, including five complete responses, giving an overall rate of 80.0% and a disease control rate of 86.6%. Two patients had stable disease and four patients progressed while using crizotinib.

“We believe that targeted therapies with response rates of more than 50% represent a major breakthrough in lung cancer therapy and should be a priority in drug development”, say lead author Julien Mazières, from Centre Hospitalier Universitaire Toulouse in France and co-authors in the Journal of Clinical Oncology.

Acknowledging that because ROS1 rearrangements are rare, a registration trial would be lengthy, the team therefore recommends that “patients with a ROS1 fusion and for whom an active targeted therapy exists should have accelerated access to precision medical treatment through collaborative trials, international programs, and national registries.”

Editorialist Benjamin Solomon, from the Peter MacCallum Cancer Centre in East Melbourne, Victoria, Australia, commends the researchers on their study, noting that the results independently validate those of an ongoing study of crizotinib in ROS1-rearranged lung cancer patients in the USA, Korea and Australia.

“The validation of ROS1 gene rearrangements as an actionable target in [non-small-cell lung cancer], along with EGFR mutations and ALK Gene rearrangements, confirms the value of screening large populations to identify small groups with rare molecular drivers”, he writes.

Julien Mazières et al also report that the EUROS1 patients had been treated with up to three or more chemotherapy lines before crizotinib; 84% had received pemetrexed and achieved a median PFS of 7.2 months during treatment.

This “encouraging activity” in ROS1-positive patients is consistent with the pemetrexed efficacy found for ALK-positive patients, the authors observe, although they emphasise that these preliminary results should not be used to guide chemotherapy choices for ROS1-positive patients.

References

Mazières J, Zalcman G, Crinò L, et al. Crizotinib therapy for advanced lung adenocarcinoma and a ROS1 rearrangement: Results from the EUROS1 Cohort. J Clin Oncol 2015; Published online before print 9 February. doi: 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; Published online before print 9 February. doi: 10.1200/JCO.2014.59.8334

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