Radiological imaging markers predicting clinical outcome in patients with metastatic colorectal carcinoma treated with regorafenib: post hoc analysis of the CORRECT phase III trial (RadioCORRECT study)

Abstract

ObjectiveTo identify imaging markers predicting clinical outcomes to regorafenib in metastatic colorectal carcinoma (mCRC).MethodsThe RadioCORRECT study is a post hoc analysis of a cohort of patients with mCRC treated within the phase III placebo-controlled CORRECT trial of regorafenib. Baseline and week 8 contrast-enhanced CT were used to assess response by RECIST 1.1, changes in the sum of target lesion diameters (ΔSTL), lung metastases cavitation and liver metastases density. Primary and secondary objectives were to develop ex novo univariable and multivariable models to predict overall survival (OS) and progression-free survival (PFS), respectively.Results202 patients were enrolled, 134 (66.3%) treated with regorafenib and 68 (33.7%) with placebo. In the univariate analysis, PFS predictors were lung metastases cavitation at baseline (HR 0.50, 95% CI 0.27 to 0.92, p=0.03) and at week 8 (HR 0.58, 95% CI 0.36 to 0.93, p=0.02). Baseline cavitation (HR 0.23, 95% CI 0.08 to 0.66, p=0.007), RECIST 1.1 (HR 0.23, 95% CI 0.14 to 0.4, p <0.0001) and ΔSTL (HR 1.16, 95% CI 1.06 to 1.27, p=0.002) predicted OS. We found an increase of 9% of diameter as the best threshold for discriminating OS (HR 2.64, 95% CI 1.61 to 4.34, p <0.001). In the multivariate analysis, baseline and week 8 cavitation remained significant PFS predictors. Baseline cavitation, RECIST 1.1 and ΔSTL remained predictors of OS in exploratory multivariable models. Assessment of liver metastases density did not predict clinical outcome.ConclusionsRECIST 1.1 and ΔSTL predict favourable outcome to regorafenib. In contrast to liver metastases density that failed to be a predictor, lung metastases cavitation represents a novel radiological marker of favourable outcome that deserves consideration.

Treatment decisions in metastatic colorectal cancer – Beyond first and second line combination therapies

“…Recently, a retrospective analysis of patients having undergone treatment with regorafenib showed that the radiologic occurrence of cavitation to lung metastasis is associated with favorable outcome [26].…”

Evolving role of regorafenib for the treatment of advanced cancers

“…As aforementioned, TTP in RESORCE did not differ between RECIST v1.1 and mRECIST, highlighting the need to develop better tools to capture treatment benefit. However, recent studies suggest that imaging techniques may predict response to regorafenib, and this represents an area of active research [107,[115][116][117]. Some studies have shown that small changes in tumor density and size or early cavitation of lung metastases could predict response to regorafenib [115][116][117].…”

“…However, recent studies suggest that imaging techniques may predict response to regorafenib, and this represents an area of active research [107,[115][116][117]. Some studies have shown that small changes in tumor density and size or early cavitation of lung metastases could predict response to regorafenib [115][116][117]. A post hoc analysis of CORRECT (RadioCORRECT) showed that cavitation in pulmonary metastases, seen with contrast-enhanced computed tomography, was associated with absence of progression at Week 8 in regorafenib-treated patients with mCRC [117].…”

Third- or Later-line Therapy for Metastatic Colorectal Cancer: Reviewing Best Practice

“…Changes such as density reduction in lung metastases, lung metastases cavitation, and longer time from first diagnosis to metastatic disease have been associated with favorable responses to regorafenib in clinical studies. 37,80,81 Such events may encourage clinicians and patients to persist with therapy, using dose adjustments to manage toxicities when necessary. 14,19,23,[82][83][84][85][86][87] However, more evidence is required to determine whether such clinical responses could be used as robust markers that inform clinical decisions.…”