Outcomes by disease status in patients with advanced biliary tract cancer treated with durvalumab or placebo plus gemcitabine and cisplatin in the phase 3 TOPAZ-1 study
Okusaka, T. Kitano, M. Chen, M. Chen, J. Ostwal, V. McNamara, Mairead G Breder, V. Petrova, M. Buchschacher, G. Rokutanda, N.
Okusaka, T.
Kitano, M.
Chen, M.
Chen, J.
Ostwal, V.
McNamara, Mairead G
Breder, V.
Petrova, M.
Buchschacher, G.
Rokutanda, N.
Citations
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Abstract
Background: TOPAZ-1 (NCT03875235) was a randomised, double-blind, global, phase
3 study evaluating the efficacy and safety of durvalumab plus gemcitabine and
cisplatin (durvalumab) as first-line treatment for patients with advanced biliary tract
cancer (BTC; Oh D-Y, et al. J Clin Oncol 2022;40[suppl 4]. Abs 378). Durvalumab
significantly improved overall survival (OS) versus placebo plus gemcitabine and
cisplatin (placebo) and represents a potential new treatment option for patients with
advanced BTC. In BTC, disease status at baseline (initially unresectable vs recurrent
[>6 months after surgery with curative intent or >6 months after adjuvant therapy])
may impact response to treatment.
Methods: The aim of this exploratory subgroup analysis of TOPAZ-1 was to assess
efficacy outcomes by disease status at baseline in patients receiving durvalumab
versus placebo. Patients with BTC were randomised 1:1 to receive durvalumab (1500
mg) or placebo on Day 1 Q3W, plus gemcitabine (1000 mg/m2) and cisplatin (25 mg/
m2) on Day 1 and 8 Q3W, for up to 8 cycles, followed by durvalumab or placebo
monotherapy until disease progression, unacceptable toxicity or other discontinua-
tion criteria were met. Randomisation was stratified by disease status and primary
tumour location (intrahepatic cholangiocarcinoma vs extrahepatic chol-
angiocarcinoma vs gallbladder cancer). Subgroup analysis of OS, progression-free
survival (PFS), objective response rate (ORR) and duration of response (DoR) per
RECIST v1.1 by disease status at baseline (initially unresectable or recurrent) was
performed. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for
OS and PFS using a Cox proportional hazards model, and odds ratios (ORs) and 95%
CIs for ORR were calculated using the Cochran-Mantel Haenszel test.
Results: The study included more patients with initially unresectable than recurrent
disease (durvalumab, n¼274 [80.4%] vs n¼67 [19.6%]; placebo, n¼279 [81.1%] vs
n¼64 [18.6%]). HRs for OS favoured durvalumab for both initially unresectable (0.84;
95% CI, 0.69e1.03) and recurrent (0.56; 95% CI, 0.32e0.96) disease; HRs for PFS also
favoured durvalumab in both subgroups (0.79; 95% CI 0.66e0.95 and 0.63; 95% CI
0.42e0.94, respectively). ORs for ORR favoured durvalumab for both initially unre-
sectable (1.61; 95% CI, 1.06e2.45) and recurrent (1.52; 95% CI 0.73e3.18) disease.
Median DoR for durvalumab versus placebo was 6.0 versus 5.1 months for initially
unresectable, and 9.7 versus 7.9 months for recurrent disease. Percentage of re-
sponders with a DoR of at least 9 and 12 months was numerically higher with dur-
valumab versus placebo for both initially unresectable (9-month, 21.5% vs 20.3%; 12-
month, 16.7% vs 10.7%) and recurrent (9 months, 58.8% vs 38.1%; 12 months, 48.1%
vs 25.4%) disease.
Conclusions: In TOPAZ-1, addition of durvalumab to GemCis improved efficacy out-
comes both in patients with initially unresectable and patients with recurrent disease
at baseline, though the relative benefit versus placebo appears greater for recurrent
compared with initially unresectable disease. These findings support the use of dur-
valumab plus GemCis as a potential new treatment option for patients with advanced
BTC, irrespective of disease status.
Description
Date
2022
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Okusaka T, Kitano M, Chen M, Chen J, Ostwal V, McNamara M, et al. Outcomes by disease status in patients with advanced biliary tract cancer treated with durvalumab or placebo plus gemcitabine and cisplatin in the phase 3 TOPAZ-1 study. Annals of Oncology. 2022 Jun;33:S242-S. PubMed PMID: WOS:000823826500009.