Abstract
CAP7.1 is a novel topoisomerase II inhibitor, converted to active etoposide via carboxylesterase 2 (CES2), with signals of efficacy in treatment-refractory solid tumours. In a Phase II trial, 27 patients with advanced biliary tract cancers (BTC) were randomised 1:1 to CAP7.1 plus best supportive care (BSC), or BSC alone, with crossover to CAP7.1 upon disease progression. The primary objective was disease control rate (DCR) following 28-day cycles of CAP7.1 (200/150 mg/m2; iv), or BSC until progression. Secondary objectives included progression-free survival (PFS), time-to-treatment failure (TTF), overall survival (OS) and safety. Fourteen patients received CAP7.1 and 13 BSC. DCR favoured CAP7.1 vs. BSC (50% vs. 20%; treatment difference: 30%, 95%CI -18.44, 69.22, full analysis set [FAS]), with disease progression in 40% vs. 70%, respectively. Significantly longer median PFS was achieved for CAP7.1 vs. BSC: 66 vs. 39 days, respectively (hazard ratio [HR] 0.31; 95%CI 0.11, 0.86; p = 0.009; FAS). Similar trends were observed for TTF and OS. CES2-positive patients had longer median PFS (158 vs. 56 days) and OS (228 vs. 82 days) vs. CES2-negative patients. Adverse events were predictable, dose-dependent and consistent with those previously observed with etoposide. These efficacy and safety findings in second-line BTC warrant further clinical investigation of CAP7.1.
Highlights
Biliary tract cancers (BTC) including intrahepatic, perihilar and distal cholangiocarcinoma (CCA) as well as gallbladder cancer (GBC) are rare diseases [1]
The safety analysis set (SAS) contained 23 patients: 13 receiving CAP7.1 and 10 initially randomised to best supportive care (BSC) who crossed over following disease progression
Three patients who were randomised to BSC who crossed over following disease progression
Summary
Biliary tract cancers (BTC) including intrahepatic, perihilar and distal cholangiocarcinoma (CCA) as well as gallbladder cancer (GBC) are rare diseases [1]. Global burden of disease estimates suggest that of the 8.9 million deaths caused by neoplasms in 2016, 161,600 were due to BTC [2]. The incidence and mortality of BTC are increasing, making it one of the fastest rising cancers worldwide [3,4,5,6]. Prognosis for BTC is poor; where surgery is a potential curative option, 5-year survival is 33.3%, but it is only 4.1% for unresectable tumours [7,8]. Most patients present with unresectable disease and, standard of care focuses on relieving symptoms [1,9]. Chemotherapy treatment depends on performance status, and with few regimens available, there is no clear survival advantage of one regimen over another [1,9]
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