RET fusions in a small subset of advanced colorectal cancers at risk of being neglected Journal Article
| Authors: | Pietrantonio, F.; Di Nicolantonio, F.; Schrock, A. B.; Lee, J.; Morano, F.; Fucà, G.; Nikolinakos, P.; Drilon, A.; Hechtman, J. F.; Christiansen, J.; Gowen, K.; Frampton, G. M.; Gasparini, P.; Rossini, D.; Gigliotti, C.; Kim, S. T.; Prisciandaro, M.; Hodgson, J.; Zaniboni, A.; Chiu, V. K.; Milione, M.; Patel, R.; Miller, V.; Bardelli, A.; Novara, L.; Wang, L.; Pupa, S. M.; Sozzi, G.; Ross, J.; Di Bartolomeo, M.; Bertotti, A.; Ali, S.; Trusolino, L.; Falcone, A.; de Braud, F.; Cremolini, C. |
| Article Title: | RET fusions in a small subset of advanced colorectal cancers at risk of being neglected |
| Abstract: | Background: Recognition of rare molecular subgroups is a challenge for precision oncology and may lead to tissue-agnostic approval of targeted agents. Here we aimed to comprehensively characterize the clinical, pathological and molecular landscape of RET rearranged metastatic colorectal cancer (mCRC). Patients and methods: In this case series, we compared clinical, pathological and molecular characteristics of 24 RET rearranged mCRC patients with those of a control group of 291 patients with RET negative tumors. RET rearranged and RET negative mCRCs were retrieved by systematic literature review and by taking advantage of three screening sources: (i) Ignyta's phase 1/1b study on RXDX-105 (NCT01877811), (ii) cohorts screened at two Italian and one South Korean Institutions and (iii) Foundation Medicine Inc. database. Next-generation sequencing data were analyzed for RET rearranged cases. Results: RET fusions were more frequent in older patients (median age of 66 versus 60 years, P=0.052), with ECOG PS 1-2 (90% versus 50%, P=0.02), right-sided (55% versus 32%, P=0.013), previously unresected primary tumors (58% versus 21%, P < 0.001), RAS and BRAF wild-type (100% versus 40%, P < 0.001) and MSI-high (48% versus 7%, P < 0.001). Notably, 11 (26%) out of 43 patients with right-sided, RAS and BRAF wild-type tumors harbored a RET rearrangement. At a median follow-up of 45.8 months, patients with RET fusion-positive tumors showed a significantly worse OS when compared with RET-negative ones (median OS 14.0 versus 38.0 months, HR: 4.59; 95% CI, 3.64-32.66; P < 0.001). In the multivariable model, RET rearrangements were still associated with shorter OS (HR: 2.97; 95% CI, 1.25-7.07; P=0.014), while primary tumor location, RAS and BRAF mutations and MSI status were not. Conclusions: Though very rare, RET rearrangements define a new subtype of mCRC that shows poor prognosis with conventional treatments and is therefore worth of a specific management. © The Author(s) 2018. |
| Keywords: | colorectal cancer; targeted therapy; gene fusions; ret; prognosis; msi-high |
| Journal Title: | Annals of Oncology |
| Volume: | 29 |
| Issue: | 6 |
| ISSN: | 0923-7534 |
| Publisher: | Oxford University Press |
| Date Published: | 2018-06-01 |
| Start Page: | 1394 |
| End Page: | 1401 |
| Language: | English |
| DOI: | 10.1093/annonc/mdy090 |
| PROVIDER: | scopus |
| PUBMED: | 29538669 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 4 September 2018 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work