93P - Outcomes by disease status in patients with advanced biliary tract cancer treated with durvalumab or placebo plus gemcitabine and cisplatin in the phase III TOPAZ-1 study

Background

TOPAZ-1 (NCT03875235) is a randomised, double-blind, global, Phase 3 study of first-line durvalumab (D) + gemcitabine and cisplatin (GemCis) in patients (pts) with advanced biliary tract cancer (BTC). D + GemCis improved overall survival vs placebo (PBO) + GemCis, and is a potential new treatment option for advanced BTC (Oh et al. NEJM Evid 2022; https://doi.org/10.1056/EVIDoa2200015). In BTC, disease status at baseline may impact response to treatment.

Methods

This exploratory subgroup analysis of TOPAZ-1 assessed efficacy outcomes by disease status at baseline (initially unresectable or recurrent) in pts receiving D + GemCis vs PBO + GemCis. Pts were randomised 1:1 to D (1500 mg) or PBO on Day 1 Q3W, + Gem (1000 mg/m²) and Cis (25 mg/m²) on Day 1 and 8 Q3W, for ≤8 cycles, followed by D or PBO monotherapy until disease progression, unacceptable toxicity or discontinuation. Randomisation was stratified by disease status and primary tumour location (intrahepatic cholangiocarcinoma vs extrahepatic cholangiocarcinoma vs gallbladder cancer).

Results

More pts had initially unresectable vs recurrent disease (Table). Efficacy outcomes by disease status at baseline are summarised (Table). Table: 93P

Efficacy outcomes by disease status at baseline (RECIST v1.1)

^∗Calculated using a Cox proportional hazards model. ^†Calculated using the Cochran-Mantel Haenszel test. CI, confidence interval; DoR, duration of response; HR, hazard ratio; OR, odds ratio; RECIST, Response Evaluation Criteria In Solid Tumours.

Conclusions

D + GemCis improved efficacy outcomes both in pts with either initially unresectable or recurrent disease at baseline, though the relative benefit vs PBO appears greater for recurrent compared with initially unresectable disease. These findings support the use of durvalumab plus GemCis as a potential new treatment option for pts with advanced BTC, irrespective of disease status.

Clinical trial identification

NCT03875235.

Editorial acknowledgement

Medical writing support, under the direction of the authors, was provided by Elaine Groat, PhD, of CMC Connect, McCann Health Medical Communications, with funding from AstraZeneca, in accordance with Good Publication Practice (GPP3) guidelines.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

T. Okusaka: Financial Interests, Personal, Advisory Board: Daiichi-sankyo, Eisai, Nihon Servier, AstraZeneca, Incyte, Ono Pharmaceutical, FUJIFILM Toyama Chemical, Chugai Pharma; Financial Interests, Personal, Invited Speaker: AstraZeneca, Eisai, Ono Pharmaceutical, Yakut Honsha, Chugai Pharma, Eli Lilly, Nihon Servier, Incyte, Johnson & Johnson, Bristol Myers Squibb, AstraZeneca; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Chugai Pharma, Eisai, Novartis, Bristol Myers Squibb, MSD, Dainippon Sumitomo Pharma, Incyte. M. Kitano: Financial Interests, Personal, Research Grant: AbbVie and Takeda Pharmaceutical; Financial Interests, Personal, Other, Honoraria: EA Pharma. J. Chen: Financial Interests, Personal, Other, Grant/ research support: Astellas, AstraZeneca, Bristol Myers Squibb, Janssen, Lilly, Merck KGaA, MSD Oncology, Oncologie, ONO, Roche, Senhwa Biosciences, Syncore, and TTY Biopharm; Financial Interests, Personal, Other, Consulting fees: ONO. V.S. Ostwal: Financial Interests, Institutional, Other, CRC support and IP support to my institute: AstraZeneca. M.G. McNamara: Financial Interests, Personal, Other, Grant/ research support: Ipsen, NuCana, and Servier; Financial Interests, Personal, Other, Consulting fees: Incyte; Financial Interests, Personal, Other, Honoraria: Advanced Accelerator Applications. V. Breder: Financial Interests, Personal, Other, Consulting fees: Bayer, Bristol Myers Squibb Russia, Eisai, MSD, Novartis, Pfizer, Roche Russia, and Takeda; Financial Interests, Personal, Other, Travel expenses: Bayer, Bristol Myers Squibb Russia, MSD, and Roche Russia. M. Petrova: Financial Interests, Personal, Invited Speaker: Astra Zeneka, EwoPharm, Takeda; Financial Interests, Personal, Advisory Board: Servie, Roche; Non-Financial Interests, Personal, Principal Investigator: Astra Zeneka, Sanofi. G. Buchschacher: Financial Interests, Institutional, Other, funding, provision of study materials, medical writing: AstraZeneca. N. Rokutanda: Financial Interests, Personal, Full or part-time Employment: AstraZenea; Financial Interests, Personal, Stocks/Shares: AstraZenea. J. Xiong: Financial Interests, Personal, Other, Former employee: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. G. Cohen: Financial Interests, Personal, Full or part-time Employment, I am a full time employee of AstraZeneca. Position is Global Clinical Lead in Immuno-oncology: AstraZeneca; Financial Interests, Personal, Stocks/Shares, Own stock in the company as an employee.: AstraZeneca. D. Oh: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, Genentech/Roche, Merck Serono, Bayer, Taiho, ASLAN, Halozyme, Zymeworks, BMS/Celgene, BeiGene, Basilea, Turning Point, Yuhan, Arcus Biosciences, IQVIA; Financial Interests, Institutional, Research Grant: AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, MSD, Handok. All other authors have declared no conflicts of interest.