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

• Published in: ESMO open Vol. 7; no. 1; p. 100314
• Main Authors: Javle, M.M., Oh, D.-Y., Ikeda, M., Yong, W.-P., Hsu, K., Lindmark, B., McIntyre, N., Firth, C.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2022; Elsevier
• Subjects: advanced; Antineoplastic Combined Chemotherapy Protocols - adverse effects; biliary tract cancer; Biliary Tract Neoplasms - drug therapy; Biliary Tract Neoplasms - pathology; capecitabine; Capecitabine - pharmacology; Capecitabine - therapeutic use; Double-Blind Method; Female; Humans; metastatic; Original Research; phase II randomized trial; Progression-Free Survival; second-line; TreeTopp; varlitinib; biliary tract cancer; TreeTopp; capecitabine; second-line; metastatic; advanced; phase II randomized trial; varlitinib
• ISSN: 2059-7029; 2059-7029
• DOI: 10.1016/j.esmoop.2021.100314

Patients with advanced biliary tract cancer who progress on first-line therapy have limited treatment options. The TreeTopp study assessed varlitinib, a reversible small molecule pan-human epidermal growth factor receptor inhibitor, plus capecitabine in previously treated advanced biliary tract cancer. This global, double-blind, randomized, placebo-controlled phase II study enrolled patients with confirmed unresectable or metastatic biliary tract cancer and disease progression after one prior line of gemcitabine-containing chemotherapy. Patients received oral varlitinib 300 mg or placebo twice daily (b.i.d.) for 21 days, plus oral capecitabine 1000 mg/m2 b.i.d. on days 1-14, in 21-day treatment cycles. Co-primary endpoints were objective response rate and progression-free survival (PFS) according to RECIST v1.1 by Independent Central Review. In total, 127 patients received varlitinib plus capecitabine (n = 64) or placebo plus capecitabine (n = 63). The objective response rate was 9.4% with varlitinib plus capecitabine versus 4.8% with capecitabine alone (odds ratio 2.28; P = 0.42). Median PFS was 2.83 versus 2.79 months [hazard ratio (HR), 0.90; 95% confidence interval (CI), 0.60-1.37; P = 0.63] and overall survival was 7.8 versus 7.5 months (HR, 1.11; 95% CI, 0.69-1.79; P = 0.66), respectively. In a subgroup analysis, the addition of varlitinib appeared to provide a PFS benefit in female patients (median, 4.1 versus 2.8 months; HR, 0.59; 95% CI, 0.28-1.23) and those with gallbladder cancer (median, 2.9 versus 1.6 months; HR, 0.55; 95% CI, 0.26-1.19). Grade ≥3 treatment-emergent adverse events were reported in 65.6% of patients receiving varlitinib plus capecitabine versus 58.7% of those receiving capecitabine alone. In patients with advanced biliary tract cancer, second-line treatment with varlitinib plus capecitabine was well tolerated but did not improve efficacy versus capecitabine alone. A PFS benefit was suggested in female patients and those with gallbladder cancer. •In advanced biliary tract cancer, second-line varlitinib plus capecitabine did not improve efficacy versus capecitabine alone.•Varlitinib was well tolerated in combination with capecitabine.•Subgroup analyses suggested varlitinib plus capecitabine may benefit female patients and those with gallbladder cancer.