Meeting
2022 ASCO Gastrointestinal Cancers Symposium
A phase 3 randomized, double-blind, placebo-controlled study of durvalumab in combination with gemcitabine plus cisplatin (GemCis) in patients (pts) with advanced biliary tract cancer (BTC): TOPAZ-1.
Authors
Do-Youn Oh
Division of Medical Oncology, Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea
Do-Youn Oh , Aiwu Ruth He , Shukui Qin , Li-Tzong Chen , Takuji Okusaka , Arndt Vogel , Jin Won Kim , Thatthan Suksombooncharoen , Myung Ah Lee , Masayuki Kitano , Howard A. Burris III , Mohamed Bouattour , Suebpong Tanasanvimon , Renata Zaucha , Antonio Avallone , Juan Cundom , Nana Rokutanda , Julia Xiong , Gordon Cohen , Juan W. Valle
Organizations
Division of Medical Oncology, Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea, Georgetown University, Washington, DC, Cancer Center of Nanjing, Jinling Hospital, Nanjing, China, National Institute of Cancer Research, Tainan, Taiwan, Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan, Hannover Medical School, Hannover, Germany, Seoul National University Bundang Hospital, Seongnam, South Korea, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand, Seoul St. Mary's Hospital, Catholic University, Seoul, South Korea, Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN, AP-HP Hôpital Beaujon, Paris, France, Department of Internal Medicine, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand, Medical University of Gdańsk, Gdańsk, Poland, Istituto Nazionale Tumori-IRCCS Fondazione G. Pascale, Naples, Italy, Instituto de Investigaciones Metabólicas, Buenos Aires, Argentina, AstraZeneca, Gaithersburg, MD, AstraZeneca, Boston, MA, University of Manchester and the Christie NHS Foundation Trust, Manchester, United Kingdom
Research Funding
Pharmaceutical/Biotech Company
Background: BTC is a rare, heterogenous cancer with poor prognosis. Reports on immunogenic features of BTC suggest checkpoint inhibition may result in antitumor immune responses, and limited clinical activity has been seen with single agents in advanced settings. Durvalumab (PD-L1 inhibitor) + GemCis showed promising antitumor activity in advanced BTC in a phase 2 study. TOPAZ-1 (NCT03875235) is the first global phase 3 study to evaluate first-line immunotherapy + GemCis in advanced BTC. Methods: In this double-blind study, pts previously untreated for unresectable locally advanced, recurrent, or metastatic BTC were randomized 1:1 to receive durvalumab (1500 mg every 3 weeks [Q3W]) or placebo + GemCis (Gem 1000 mg/m2 and Cis 25 mg/m2 on Days 1 and 8 Q3W) for up to 8 cycles, followed by durvalumab (1500 mg Q4W) or placebo until disease progression or unacceptable toxicity. Randomization was stratified by disease status (initially unresectable, recurrent) and primary tumor location (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer). The primary objective was to assess overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. Results: At data cutoff for this interim analysis (11 August 2021), 685 pts were randomized to durvalumab + GemCis (n=341) or placebo + GemCis (n=344; Table). The primary objective was met: durvalumab + GemCis significantly improved OS vs placebo + GemCis (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.66–0.97; p=0.021). PFS was also significantly improved with durvalumab vs placebo (HR, 0.75; 95% CI, 0.64–0.89; p=0.001). ORR was 26.7% with durvalumab and 18.7% with placebo. Grade 3/4 treatment-related adverse events (TRAEs) occurred in 62.7% of pts receiving durvalumab and 64.9% of pts receiving placebo. TRAEs led to discontinuation of any study medication in 8.9% of pts receiving durvalumab and 11.4% of pts receiving placebo. Conclusions: In pts with advanced BTC, durvalumab + GemCis significantly improved OS and PFS vs placebo + GemCis with manageable safety, indicating durvalumab + GemCis may be a new first-line standard of care regimen. Clinical trial information: NCT03875235.
| Durvalumab + GemCis (N=341) | Placebo + GemCis (N=344) | |
|---|---|---|
| Median age (range), y | 64 (20–84) | 64 (31–85) |
| Female, % | 50.4 | 48.8 |
| ECOG PS 0, % | 50.7 | 47.4 |
| Median follow-up, mo | 13.7 | 12.6 |
| Median OS (95% CI), mo | 12.8 (11.1–14.0) | 11.5 (10.1–12.5) |
| 18-month OS (95% CI), % | 35.1 (29.1–41.2) | 25.6 (19.9–31.7) |
| 24-month OS (95% CI), % | 24.9 (17.9–32.5) | 10.4 (4.7–18.8) |
| Median PFS (95% CI), mo | 7.2 (6.7–7.4) | 5.7 (5.6–6.7) |
| Grade 3/4 AEs, n (%)* | 256 (75.7) | 266 (77.8) |
| TRAEs leading to death, n (%)* | 2 (0.6) | 1 (0.3) |
*Safety data percentages are calculated from the safety population (n=338 for durvalumab + GemCis and n=342 for placebo + GemCis).
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Abstract Details
Session Type
Oral Abstract Session
Session Title
Oral Abstract Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Track
Pancreatic Cancer,Hepatobiliary Cancer,Neuroendocrine/Carcinoid,Small Bowel Cancer
Sub Track
Therapeutics
Clinical Trial Registration Number
NCT03875235
DOI
10.1200/JCO.2022.40.4_suppl.378
Abstract #
378
Abstract Disclosures
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