Outcomes by primary tumour location in patients with advanced biliary tract cancer treated with durvalumab or placebo plus gemcitabine and cisplatin in the phase 3 TOPAZ-1 study
He, A. Lee, C. Ikeda, M. Potemski, P. Morizane, C. Cundom, J. Tougeron, D. Dayyani, F. Rokutanda, N.
He, A.
Lee, C.
Ikeda, M.
Potemski, P.
Morizane, C.
Cundom, J.
Tougeron, D.
Dayyani, F.
Rokutanda, N.
Citations
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Abstract
Background: The double-blind, phase 3 TOPAZ-1 study (NCT03875235) evaluated the
efficacy and safety of durvalumab plus gemcitabine and cisplatin (GemCis) 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 plus GemCis significantly improved
overall survival (OS) versus placebo plus GemCis and represents a potential new first-
line treatment option. In BTC, primary tumour location (intrahepatic or extrahepatic
cholangiocarcinoma [IHCC/EHCC], or gallbladder cancer [GBC]) may impact risk fac-
tors, prognoses, and response to treatment.
Methods: The aim of this exploratory subgroup analysis of TOPAZ-1 was to assess
efficacy outcomes, OS, progression-free survival (PFS), objective response rate (ORR)
and duration of response (DoR) per RECIST v1.1, by primary tumour location in pa-
tients 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 discontinuation criteria were met. Randomisation was stratified by disease
status (initially unresectable vs recurrent) and primary tumour location (IHCC vs EHCC
vs GBC). 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: Patient numbers with IHCC, EHCC and GBC were balanced between treatment
arms; more patients had IHCC than EHCC or GBC (durvalumab: n¼190, n¼66, n¼85;
placebo: n¼193, n¼65, n¼86, respectively). HRs for OS favoured durvalumab: HR was
0.76 (95% CI, 0.58-0.98) for IHCC, 0.76 (95% CI, 0.49-1.19) for EHCC, and 0.94 (95% CI,
0.65-1.37) for GBC. To aid in understanding the higher HR in GBC, regional analysis was
performed: the OS HR for GBC in Asia was 0.82 (95% CI, 0.48-1.40) and in Europe plus
North America (non-Asian countries minus South America) was 0.78 (95% CI, 0.44-1.37).
PFS HR was 0.79 (95% CI, 0.64-0.99) for IHCC, 0.52 (95% CI, 0.35-0.78) for EHCC, and
0.90 (95% CI, 0.65-1.24) for GBC. ORR favoured durvalumab in IHCC (24.7% vs 15.5%;
OR, 1.79; 95% CI, 1.07-2.97), EHCC (28.8% vs 15.6%; OR, 2.18; 95% CI, 0.92-5.16) and
GBC (29.4% vs 27.9%; OR, 1.08; 95% CI, 0.55-2.09). Percentages of responders with a
DoR of at least 9 and 12 months were higher with durvalumab versus placebo for all
tumour locations (9-month: IHCC 28.3% vs 24.0%, EHCC 43.3% vs 23.3%, GBC 33.2% vs
27.5%; 12-month: IHCC 18.9% vs 12.0%, EHCC 43.3% vs 23.3%, GBC 27.6% vs 16.5%).
Conclusions: In TOPAZ-1, the addition of durvalumab to GemCis appeared to improve
efficacy outcomes (not formally tested for subgroup comparisons) for patients with
IHCC, EHCC and GBC. Though the magnitude of efficacy improvement varied slightly
between primary tumour locations, the benefit of durvalumab was observed
consistently. These findings support durvalumab plus GemCis as a treatment option
for BTC, irrespective of primary tumour location.
Description
Date
2022
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
He A, Valle J, Lee C, Ikeda M, Potemski P, Morizane C, et al. Outcomes by primary tumour location 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:S378-S. PubMed PMID: WOS:000823826500365.