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: 1) Ignyta's phase 1/1b study on RXDX-105 (
NCT01877811); 2) cohorts screened at two Italian and one South Korean Institutions; 3) 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 vs. 60 years, p = 0.052), with ECOG PS 1-2 (90% vs. 50%, p = 0.02), right-sided (55% vs. 32%,
P=0.013), previously unresected primary tumors (58% vs. 21%,
P<0.001),
RAS and
BRAF wild-type (100% vs. 40%, p < 0.001) and MSI-high (48% vs. 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 vs. 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.
from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2oXz9YO
