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345 Background: A high clinical unmet need remains in treating advanced or metastatic biliary tract cancers (BTC) after failure of gemcitabine and platinum-based chemotherapy, with no standard of care. Regorafenib is potent oral multi-kinase inhibitor of kinases involved in tumor angiogenesis, oncogenesis and tumor microenvironment. It has demonstrated efficacy and acceptable safety in some GI tumors that have progressed on standard therapies. Methods: REACHIN (NCT02162914) is a multicenter double-blinded placebo-controlled randomized phase II study to evaluate the safety and efficacy of regorafenib (REG) in patients with locally advanced (non resectable) and metastatic histologically proven BTC, progressing after gemcitabine-platinum. 66 patients were randomized (1:1) to receive BSC plus REG160 mg od, 3 weeks on/ one week off (cycle = 4 weeks) or BSC + placebo (P) until progression or unacceptable toxicity. Sample size calculation was based on the logrank test, assuming a one-sided significance of 10%, 80% power, and an improvement in median PFS of 50% (6 to 12 weeks in the REG group). Primary endpoint is PFS. Secondary endpoints are response rate and OS. Results: Between May 2014 and February 2018, 68 (33 REG, 35 P) patients have been included (2 patients died before starting treatment and were replaced). Of 66 patients treated (26 F/ 40 M), tumors were intra-hepatic and hilar (n = 48), extra-hepatic (n = 10) and gallbladder (n = 8). One patient remains on REG treatment. Median PFS for REG is 3.0 months (95% CI: 2.3-4.9) and 1.5 months (95% CI : 1.2-2.0) for P with a HR of 0.48 (95% CI : 0.29-0.80), p = 0.004. Rates of PR+SD are 23/33 (70%) for REG and 11/33 (33%) for P (p = 0,002). Median treatment duration is 10,9 weeks for REG vs 6,3 weeks for P (p = 0,004). Dose reductions were applied in 14/33 patients in REG and in 5/33 patients in P. There is no unexpected/new safety signal. Median OS is 5.3 months for REG and 5.1 months for P (p = 0.21). Conclusions: Regorafenib significantly increases median PFS and tumor control in patients with previously treated metastatic/ unresectable biliary tract cancer. Clinical trial information: NCT02162914.

Background Tumoral heterogeneity is a major determinant of resistance in solid tumors. FDG-PET/CT can identify early during chemotherapy non-responsive lesions within the whole body tumor load. This prospective multicentric proof-of-concept study explores intra-individual metabolic response (mR) heterogeneity as a treatment efficacy biomarker in chemorefractory metastatic colorectal cancer (mCRC). Methods Standardized FDG-PET/CT was performed at baseline and after the first cycle of combined sorafenib (600mg/day for 21 days, then 800mg/day) and capecitabine (1700 mg/m2/day administered D1-14 every 21 days). MR assessment was categorized according to the proportion of metabolically non-responding (non-mR) lesions (stable FDG uptake with SUV-max decrease, SCOPUS: ar.j, info:eu-repo/semantics/published

Background: Surgery is a curative treatment for patients with locally advanced colon cancer, but recurrences are frequent for those with stage III disease. FOLFOX adjuvant chemotherapy has been shown to improve recurrence-free survival and overall survival by more than 20% and is nowadays considered a standard of care. However, the vast majority of patients will not benefit from receiving cytotoxic drugs because they have either already been cured by surgery or because their tumor cells are resistant to the chemotherapy, for which predictive factors are still not available.Identifying which patients are unlikely to respond to adjuvant chemotherapy from among those who are eligible for such treatment would be a major step towards treatment personalization. It would spare such patients from unnecessary toxicities and would improve the allocation of societal healthcare resources.Methods/design: PePiTA is a prospective, multicenter, non-randomised trial built on the hypothesis that preoperative chemosensitivity testing using FDG-PET/CT before and after one course of FOLFOX can identify the patients who are unlikely to benefit from 6 months of adjuvant FOLFOX treatment for stage III colon cancer.The study's primary objective is to examine the ability of PET/CT-assessed tumor FDG uptake after one course of preoperative chemotherapy to predict the outcome of adjuvant therapy, as measured by 3-year disease-free survival.Secondary objectives are to examine the predictive value of changes in PET/CT-assessed tumor FDG uptake on overall survival, to define the best cut-off value of FDG uptake for predicting treatment outcome, and to analyse the cost-effectiveness of such preoperative chemo-sensitivity testing.At study planning, exploratory translational research objectives were 1) to assess the predictive value of circulating tumor cells for disease-free survival, 2) to examine the predictive value of single nucleotide polymorphisms for disease-free survival with respect to genes related either to toxicity or to drug targets, 3) to assess genomic rearrangements associated with response or resistance to FOLFOX treatment, 4) to identify an immunologic signature associated with metabolic tumor response to FOLFOX therapy and, finally, 5) to create a bank of frozen tumor samples for future studies.Discussion: PePiTA is the first study to use the primitive tumor chemosensitivity assessed by metabolic imaging as a guidance for adjuvant therapy in colon cancer. It could pave the way for tailoring the treatment and avoiding useless toxicities for the patients and inadequate expenses for the society. It could also give an interesting insight into tumoral heterogeneity, resistance to chemotherapy, genetic predisposants to oxaliplatin toxicity and immune response to cancer.EudraCT number: 2009-011445-13. Trial registration: ClinicalTrials.gov number, NCT00994864. © 2013 Hendlisz et al. licensee BioMed Central Ltd., SCOPUS: ar.j, info:eu-repo/semantics/published