Varlitinib plus capecitabine in second-line advanced biliary tract cancer: a randomized, phase II study (TreeTopp)

Area of Science:

• Oncology
• Medical Research

Background:

• Advanced biliary tract cancer (BTC) presents limited treatment options after first-line therapy failure.
• Varlitinib, a pan-human epidermal growth factor receptor inhibitor, was investigated in previously treated advanced BTC patients.

Purpose of the Study:

• To evaluate the efficacy and safety of varlitinib combined with capecitabine as a second-line treatment for advanced biliary tract cancer.
• To assess objective response rate and progression-free survival (PFS) in this patient population.

Main Methods:

• A global, double-blind, randomized, placebo-controlled phase II study (TreeTopp) enrolled 127 patients with advanced BTC progressing after gemcitabine-based chemotherapy.
• Patients received oral varlitinib or placebo twice daily, plus oral capecitabine, in 21-day cycles.
• Co-primary endpoints included objective response rate and PFS by Independent Central Review using RECIST v1.1 criteria.

Main Results:

• The objective response rate was 9.4% for varlitinib plus capecitabine versus 4.8% for placebo plus capecitabine (P=0.42).
• Median PFS was 2.83 months versus 2.79 months (HR 0.90; P=0.63), and median overall survival was 7.8 versus 7.5 months (HR 1.11; P=0.66).
• Subgroup analyses suggested a PFS benefit for female patients and those with gallbladder cancer. Grade ≥3 adverse events occurred in 65.6% vs 58.7% of patients.

Conclusions:

• Second-line varlitinib plus capecitabine was well-tolerated but did not significantly improve efficacy compared to capecitabine alone in advanced BTC.
• A potential PFS benefit was suggested in specific subgroups: female patients and those with gallbladder cancer.