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

M M Javle; D-Y Oh; M Ikeda; W-P Yong; K Hsu; B Lindmark; N McIntyre; C Firth

doi:10.1016/j.esmoop.2021.100314

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

ESMO Open. 2022 Feb;7(1):100314. doi: 10.1016/j.esmoop.2021.100314. Epub 2021 Dec 15.

Authors

M M Javle¹, D-Y Oh², M Ikeda³, W-P Yong⁴, K Hsu⁵, B Lindmark⁵, N McIntyre⁵, C Firth⁵

Affiliations

¹ Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA. Electronic address: mjavle@mdanderson.org.
² Division of Medical Oncology, Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, South Korea.
³ Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
⁴ Department of Haematology-Oncology, National University Cancer Institute, Cancer Science Institute, Singapore, Singapore.
⁵ ASLAN Pharmaceuticals, Singapore, Singapore.

Abstract

Background: 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.

Patients and methods: 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.

Results: 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.

Conclusions: 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.

Keywords: TreeTopp; advanced; biliary tract cancer; capecitabine; metastatic; phase II randomized trial; second-line; varlitinib.

Publication types

Clinical Trial, Phase II
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Combined Chemotherapy Protocols* / adverse effects
Biliary Tract Neoplasms* / drug therapy
Biliary Tract Neoplasms* / pathology
Capecitabine / pharmacology
Capecitabine / therapeutic use
Double-Blind Method
Female
Humans
Progression-Free Survival

Substances

Capecitabine