TY - JOUR
T1 - Varlitinib plus capecitabine in second-line advanced biliary tract cancer
T2 - a randomized, phase II study (TreeTopp)
AU - Javle, M. M.
AU - Oh, D. Y.
AU - Ikeda, M.
AU - Yong, W. P.
AU - Hsu, K.
AU - Lindmark, B.
AU - McIntyre, N.
AU - Firth, C.
N1 - Funding Information:
The authors wish to thank all patients, investigators, and coordinators who participated in the study. Medical writing support was provided by Dr Sharon Gladwin, PhD from Rude Health Consulting, and was funded by ASLAN Pharmaceuticals.
Funding Information:
The authors wish to thank all patients, investigators, and coordinators who participated in the study. Medical writing support was provided by Dr Sharon Gladwin, PhD from Rude Health Consulting, and was funded by ASLAN Pharmaceuticals. This trial was funded by ASLAN Pharmaceuticals Pte. Ltd. MMJ has served as a consultant/steering committee member for Taiho, QED, AstraZeneca, Meclun, TransThera, Bristol Myers Squibb (BMS), EMD Serono, Incyte, Nucana, and PCI, and has received research funding from EMD Serono, Merck, QED, Novartis, AstraZeneca, Basilea, Eli Lilly, ASLAN, Incyte, and Agios, and honoraria/speaker bureau fees from QED, Agios, and Incyte. D-YO has served as a consultant/advisory board member for AstraZeneca, Novartis, Genentech/Roche, Merck Serono, Bayer, Taiho, ASLAN, Halozyme, Zymeworks, BMS/Celgene, BeiGene, Basilea, and Turning Point, and has received research grants from AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, Merck Sharp & Dohme (MSD), and Handok. MI has served as an advisory board member for Eisai, Eli Lilly Japan, ASLAN, GlaxoSmithKline, Nihon Servier, Chugai, BMS, Novartis, Bayer, and Takeda, has received honoraria from Eisai, MSD, Eli Lilly Japan, Yakult, Teijin Pharma, Astellas, EA Pharma, Sumitomo Dainippon, Otsuka, Yakult, Nihon Servier, Taiho, Chugai, BMS, Novartis, Bayer, and Takeda, and has received research funding from Eisai, Merck Serono, MSD, Eli Lilly Japan, Yakult, Ono, ASLAN, J-Pharma, AstraZeneca, EA Pharma, Pfizer, Merus N.V. Nihon Servier, Delta-Fly Pharma, Chiome Bioscience, Chugai, BMS, Novartis, Bayer, and Takeda. W-PY has served as an advisory board member for ASLAN. NM is a consultant for ASLAN. BL is a former employee (at the time of the study) and current shareholder of ASLAN. CF and KH are employees and shareholders of ASLAN.
Funding Information:
This trial was funded by ASLAN Pharmaceuticals Pte. Ltd .
Publisher Copyright:
© 2021
PY - 2022/2
Y1 - 2022/2
N2 - 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.
AB - 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.
KW - TreeTopp
KW - advanced
KW - biliary tract cancer
KW - capecitabine
KW - metastatic
KW - phase II randomized trial
KW - second-line
KW - varlitinib
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U2 - 10.1016/j.esmoop.2021.100314
DO - 10.1016/j.esmoop.2021.100314
M3 - Article
C2 - 34922298
AN - SCOPUS:85121232787
SN - 2059-7029
VL - 7
JO - ESMO Open
JF - ESMO Open
IS - 1
M1 - 100314
ER -