SoMore trial: Early metabolic response assessment of a sorafenib (SOR) and capecitabine (CAP) combination in chemorefractory metastatic colorectal cancer (mCRC).

Abstract

524 Background: The SOR-CAP combination has shown clinical activity in several phase I-II trials involving metastatic breast cancer and mCRC patients (pts). SoMore aims to substantiate the combination’s effects in mCRC refractory to all medications and the predictive value of early metabolic response (MR) on survival. Methods: SoMore (EUDRACT 2010-023695-91) has 2 coprimary objectives: 1) to demonstrate an overall survival (OS) rate at 6 months (mths) > 30%, and 2) to compare OS between pts with and without MR. CAP was given at 1700 mg/m²/day (D), 2 weeks out of 3. SOR was administered at 600mg/D for the first cycle, then at 800mg/D until progression or unacceptable toxicity. FDGPET-CT was performed at baseline and before the 2nd cycle. MR analysis was centralized and blinded for the investigators. Results: From February to October 2011, 92 eligible pts were prospectively recruited in 6 Belgian centers: M/F: 54%/46%; ECOG PS 0/1: 55%/45%; median age: 61. A median of 5 treatment cycles were given (0-28+). Grade 3-4 toxic reactions were reported in 61.2%, mainly fatigue (18%), hand-foot skin reaction (14%) and diarrhea (11%), but no toxic death. 6.9% of the pts stopped therapy due to toxicity. 6 mths OS was 71% (95% CI: 61%-79%), significantly >30% (p<0.001). 47% of the 79 pts evaluable for metabolic assessment showed homogeneous MR (HMR) of all metastatic lesions, 32% mixed MR and 21% homogeneous non-MR. Median overall OS and PFS of the intent-to-treat population and of pts with and without HMR are shown in the table below. Hazard ratio for HMR was 0.34 (95% CI, 0.21 to 0.56) p-value <0.001 for PFS and 0.59 (95% CI, 0.37 to 0.96) p-value 0.03 for OS. Conclusions: These data suggest robust efficacy for the SOR-CAP combination in heavily pretreated mCRC, associated with high but manageable toxicity. Early MR assessment, by detecting unresponsive lesions within the whole body tumoral load, is able to capture the pts’ likelihood of benefit, opening the path to personalized medicine. Clinical trial information: NCT01290926. [Table: see text]

Imaging in Colorectal Cancer: Progress and Challenges for the Clinicians

“…FDG-PET/CT has proven to be valuable for evaluating responses to chemotherapy and especially for targeted treatments [ 32 ]. For example, in a multicentre setting using standardised FDG-PET/CT procedures, early metabolic response was assessed following a combination of sorafenib and capecitabine in chemorefractory mCRC patients as part of the SoMore trial [ 33 , 34 ]. After one single treatment cycle (week 3), FDG-PET/CT could differentiate responsive from unresponsive lesions [ 33 ].…”

“…For example, in a multicentre setting using standardised FDG-PET/CT procedures, early metabolic response was assessed following a combination of sorafenib and capecitabine in chemorefractory mCRC patients as part of the SoMore trial [ 33 , 34 ]. After one single treatment cycle (week 3), FDG-PET/CT could differentiate responsive from unresponsive lesions [ 33 ]. Findings such as this may support treatment decisions in the future, although further investigation is required.…”

“…A recent comparison of criteria developed by the European Organization for Research and Treatment of Cancer (EORTC) and PET Response Criteria in Solid Tumours (PERCIST) found the latter to be less ambiguous due to clear definitions and therefore deemed easier to use [ 32 ]. One of the major issues is the presence of interlesional tumour response heterogeneity, which is observed on FDG-PET/CT scans of more than 50% of patients with metastatic disease and has a negative predictive and prognostic impact [ 31 , 33 ]. The existing response criteria (both anatomical and metabolic, including those from WHO, EORTC, RECIST and PERCIST) perform an averaging or summing of a selection of target lesions, so most relevant information about the presence of individual treatment resistant lesions is lost.…”

Regorafenib assessment in refractory advanced colorectal cancer: RegARd-C study protocol

“…The results of the metabolic assessment remains blinded for the clinical investigator, and will follow a predetermined 3-step methodology previously described. 13 15 …”

“…The most important finding related to this metabolic analysis was the identification of a prognostic value for early metabolic homogeneous response. 15 Indeed, among 79 patients who underwent baseline PET examination as well as day 14 examination, 37 patients (47%) were found responding homogeneously in all their lesions to treatment with combined sorafenib–capecitabine. These patients had prolonged survival after day 14 compared to all the other patients (HR=0.59, 95% CI 0.37 to 0.96, p=0.03).…”