Clinical and molecular landscape of metastatic colorectal cancer (mCRC) harboring ALK, ROS1, or NTRK 1, 2, 3 (NTRKs) rearrangements.

589Background: ALK, ROS1, and NTRKs fusions occur in 0.2-2.4% of CRCs, and represent therapeutic targets, as indicated by promising reports of individual patients treated with tyrosine kinase inhibitors. Clinical and molecular features of mCRCs harboring these fusions have not been elucidated. Methods: mCRC harboring ALK, ROS1 and NTRKs fusions were identified taking advantage of screening programs worldwide (Ignyta STARTRK trials; Foundation Medicine Database; Memorial Sloan Kettering-IMPACT; Australian MAX trial post-hoc analysis). Clinicopathological and molecular characteristics of ALK, ROS1, NTRKs rearranged cases were compared with those of non-rearranged cases, included in Ignyta’s STARTRK trials program. Results: 27 ALK, ROS1 or NTRKs rearranged (including a novel SCYL3-NTRK1 fusion) and 319 not rearranged mCRCs patients were included. Rearrangements were more frequent in older patients (p = 0.024), and tumors that were right-sided (80% vs 30%; p < 0.001), RAS wild-type (93% vs 52%; p < 0.001), MS...