Authors
A. DEMOLS (1), I. BORBATH (2), M. VAN DEN EYNDE (2), G. HOUBIERS (3), M. PEETERS (4), R. MARÉCHAL (5), T. DELAUNOIT (6), J. GOEMINNE (7), S. LAURENT (8), S. HOLBRECHTS (9), M. PAESMANS (10), J. VAN LAETHEM (1) / [1] Hopital Erasme, ULB, , Belgium, Gastroenterology, [2] Clin universitaires St-Luc, UCL, Brussels, Belgium, Gastroenterology, [3] CHC, Liège, Belgium, Gastroenterology, [4] UZA, Universitair Ziekenhuis Antwerpen, Edegem, Belgium, Oncology, [5] CHU Tivoli, La Louvière, Belgium, Gastroenterology, [6] Hôpital de Jolimont, Haine-Saint-Paul, Belgium, Gastroenterology, [7] Clinique Sainte-Elisabeth, Namur, Belgium, Oncology, [8] UZGent, Gent, Belgium, Gastroenterology, [9] CHU Ambroise Paré MONS, Mons, Belgium, Oncology, [10] Institut Jules Bordet, Brussels, Belgium, Data center
Introduction
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.
Aim
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. Primary endpoint is PFS. Secondary endpoints are response rate and OS.
Methods
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).
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.
