Crizotinib shows promise in ROS1-rearranged advanced NSCLC

Crizotinib induced a high response rate in patients with advanced non–small cell lung cancer who harbored ROS1 rearrangements, according to study results presented at the European Society of Medical Oncology's Annual Congress in Madrid.

Alice T. Shaw, MD, PhD, a thoracic oncologist at Massachusetts General Hospital Cancer Center, and colleagues sought to evaluate the efficacy of crizotinib (Xalkori, Pfizer) — a tyrosine kinase inhibitor that targets anaplastic lymphoma kinase (ALK) and the proto-oncogene receptor tyrosine kinases MET and ROS1— in 50 patients with advanced NSCLC who tested positive for ROS1 rearrangements. All patients received 250 mg of crizotinib twice daily.

Alice T. Shaw

Three patients demonstrated a complete response, and 33 patients demonstrated a partial response. Using these data, researchers calculated an objective response rate of 72% (95% CI, 58-84).

The median duration of response was 17.6 months (95% CI, 14.5-not reached), and median PFS was 19.2 months (95% CI, 14.4-not reached). Twenty-five patients were still in follow-up for progression at the time of the analysis.

Median follow-up for OS was 16.4 months. Researchers reported a 12-month OS rate of 85% (95% CI, 72-93). Median OS had not been reached.

Researchers also evaluated ROS1 fusion partners from 30 tumor samples using next-generation sequencing and reverse-transcriptase-polymerase-chain-reaction assays.

The most common fusion partner was the gene encoding CD74 (44%). Researchers also detected four other previously known ROS1 fusions partners — SDC4, EZR, SLC34A2 and TPM3 — and two novel fusion partners, LIMA1 and MSN.

However, there was no association between the type of ROS1 rearrangement and clinical response to crizotinib.

Most treatment-related adverse events were grade 1 or grade 2 (94%). The most common adverse events were visual impairment (82%), diarrhea (44%), nausea (40%), peripheral edema (40%), constipation (34%) and vomiting (34%).

“ROS1 rearrangement defines a second molecular subgroup of NSCLC for which crizotinib is highly active,” Shaw and colleagues concluded. “These results highlight the importance of screening for this genetic alteration in patients with advanced NSCLC. Although fluorescence in situ hybridization (FISH) was used in this study, other diagnostic methods have been proposed, and further work is required to establish the most effective screening strategy for ROS1 rearrangement.”

Disclosure: The study was funded in part by Pfizer and grants from the NCI, Uniting against Lung Cancer and Be a Piece of the Solution. See the study for a full list of the researchers’ relevant financial disclosures.

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Source: Shaw AT. New Engl J Med. 2014;doi:10.1056/NEJMoa1406766.

European Society for Medical Oncology Congress

Crizotinib shows promise in ROS1-rearranged advanced NSCLC