Capecitabine plus oxaliplatin versus gemcitabine plus oxaliplatin as first-line therapy for advanced biliary tract cancers: a multicenter, open-label, randomized, phase III, noninferiority trial

Abstract

Background: Capecitabine plus oxaliplatin (XELOX) has shown modest activity and tolerable toxicity in a phase II trial for biliary tract cancers (BTCs). Meanwhile, gemcitabine plus oxaliplatin (GEMOX) has been the reference arm in recent phase II and III trials for BTCs. We aimed to investigate the efficacy of XELOX versus GEMOX as first-line therapy for advanced BCTs. Patients and methods:In this open-label, randomized, phase III, noninferiority trial, we randomly selected patients with metastatic BCTs to receive GEMOX (gemcitabine 1000 mg/m 2 on days 1 and 8, and oxaliplatin 100 mg/m 2 on day 1) or XELOX (capecitabine 1000 mg/m 2 , twice daily, on days 1-14 and oxaliplatin 130 mg/m 2 on day 1) as first-line treatment, given every 3 weeks, totaling eight cycles. The primary end point was to prove the noninferiority of XELOX to GEMOX in terms of 6-month progression-free survival (PFS) rate.Results: In total, 114 patients randomly received GEMOX and 108 randomly received XELOX. The median PFS was 5.3 months for the GEMOX group and 5.8 months for the XELOX group. The 6-month PFS rate was 44.5% for the GEMOX group and 46.7% for the XELOX group. The 95% confidence interval of the 6-month PFS rate difference between both groups was À12% to 16%, meeting the criteria for noninferiority of XELOX to GEMOX. There was no difference in objective response (P¼0.171) and median overall survival (P¼0.131) between both groups. The most common grade three to four adverse events were neutropenia and thrombocytopenia. No patient died of treatment-related causes. The XELOX group had significantly lower frequencies of hospital visits than the GEMOX group (P<0.001). Conclusion:XELOX showed significant noninferiority to GEMOX in terms of 6-month PFS rate. Thus, XELOX could be an alternative first-line treatment of BCTs.Trial Registration: This study was registered in ClinicalTrials.gov (number NCT01470443).

Camrelizumab plus gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary tract cancer: a single-arm, open-label, phase II trial

“…6 In practice, 6-8 cycles of GEMOX regimen are more frequently selected in the treatment of patients with BTC with an acceptable safety profile. 7 However, the OS is far from satisfactory and the 5-year survival rate is less than 10%. 3 Hence, there remains an unmet need to develop more effective treatment options for patients with unresectable BTC.…”

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“…The median PFS for GEMOX and XELOX was 5.3 months and 5.8 months, respectively, translating to a five-month PFS rate of 44.5% with GEMOX and 46.7% with XELOX. OS was not significantly different in the two arms, with a median OS of 10.4 and 10.6 months for GEMOX and XELOX, respectively [34] . These two studies established the clinical efficacy of GEMOX in the frontline treatment of patients with advanced biliary tract cancer, and the drug has become widely used in the treatment of patients with advanced CCA.…”

“…Recently, the GEMOX regimen was evaluated in a phase III setting, where it was compared to a combination of capecitabine (1000 mg/m 2 BID on Days 1-14) and oxaliplatin (130 mg/m 2 on Day 1) (XELOX). In that non-inferiority trial, with 222 patients with advanced biliary cancer, GEMOX and XELOX were given every three weeks for eight cycles [34] . The median PFS for GEMOX and XELOX was 5.3 months and 5.8 months, respectively, translating to a five-month PFS rate of 44.5% with GEMOX and 46.7% with XELOX.…”

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“…36 Furthermore, CAPOX was non-inferior to GEMOX in terms of 6month progression-free survival (PFS) rate in a recent phase III trial, with a better toxicity profile and less frequent hospital visits. 37 Therefore, CAPOX was recommended as the first-line treatment of choice for ECOG PS 0 to 1 patients with metastatic or unresectable BTC. For patients with liver-limited unresectable disease, we discussed, in a multidisciplinary setting, the chance for locoregional therapy (eg, yttrium-90 radioembolization), when feasible.…”