Varlitinib plus capecitabine in second-line advanced biliary tract cancer: a randomized, phase II study (TreeTopp)
1Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA.
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.
Insights
Second-line varlitinib plus capecitabine did not improve outcomes for advanced biliary tract cancer patients. However, a progression-free survival benefit was observed in female patients and those with gallbladder cancer.
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.
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