86P - Outcomes by primary tumour location 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 double-blind, Phase 3 study of durvalumab (D) + gemcitabine and cisplatin (GemCis) in patients (pts) with advanced biliary tract cancer (BTC). D + GemCis improved overall survival (OS) vs placebo (PBO) + GemCis, and is a potential new treatment option (Oh et al. NEJM Evid 2022; https://doi.org/10.1056/EVIDoa2200015). In BTC, primary tumour location may impact risk factors, prognoses and treatment response.

Methods

This exploratory subgroup analysis of TOPAZ-1 assessed efficacy outcomes by primary tumour location (intrahepatic [IHCC], extrahepatic [EHCC] cholangiocarcinoma or gall bladder cancer [GBC]). Pts were randomised 1:1 to receive 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 (initially unresectable vs recurrent) and primary tumour location (IHCC vs EHCC vs GBC).

Results

Patient numbers with IHCC, EHCC and GBC were balanced between treatment arms; more pts had IHCC than EHCC or GBC (Table). Efficacy outcomes by primary tumour location are summarised (Table). To aid in understanding the higher hazard ratio (HR) in GBC, regional analysis was performed: OS HR for GBC in Asia was 0.82 (95% confidence interval [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) Table: 86P

Efficacy outcomes by primary tumour location (RECIST v1.1)

^∗Calculated using a Cox proportional hazards model.^†Calculated using the Cochran-Mantel Haenszel test.

Conclusions

D + GemCis appeared to improve efficacy outcomes (not formally tested for subgroup comparisons) for pts with IHCC, EHCC and GBC. Findings support D + GemCis as a potential new treatment option for advanced BTC, irrespective of primary tumour location.

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

A.R. He: Financial Interests, Personal, Other, Advisory Board meeting on management of biliary cancer and HCC: AstraZeneca. J.W. Valle: Financial Interests, Personal, Advisory Board: Astra-Zeneca, Agios, QED, NuCana BioMed, Servier, Image Equipment Ltd. (AAA), Hutchinson Medipharma, Zymeworks, Sirtex, Baxter, Autem, Hutchinson Medipharma; Financial Interests, Personal, Invited Speaker: Ipsen, Mylan, Incyte; Financial Interests, Institutional, Research Grant, Grant funding for ABC-12 study: AstraZeneca; Financial Interests, Institutional, Research Grant, University of Manchester: RedX. M. Ikeda: Financial Interests, Personal, Advisory Board: AstraZeneca, Chugai, Eli Lilly Japan, Eisai, NIHON Servier, Novartis, Ono, Takeda, GlaxoSmithKline; Financial Interests, Personal, Invited Speaker: AstraZeneca, Bayer, Bristol Myers Squibb, Chugai, Eli Lilly Japan, Eisai, NIHON Servier, Novartis, Taiho, Yakult, Teijin Pharma, AbbVie, Abbott Japan, Fujifilm Toyama Chemical, Incyte Biosciences Japan, ASLAN, Chugai, NIHON SERVIER, Takeda; Financial Interests, Institutional, Invited Speaker: Bayer, Bristol Myers Squibb, Eisai, AstraZeneca, Eli Lilly Japan, Chugai Pharmaceutical, Merck Serono, MSD, Ono, Yakult, Novartis, Takeda, J-Pharma, Pfizer, Chiome Bioscience, NIHON Servier, Delta-Fly Pharma, Syneos Health, Merus.N.V. P. Potemski: Financial Interests, Personal, Other, Principal investigator Invited speaker Advisory Board: AstraZeneca; Financial Interests, Personal, Other, Principal investigator Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Ipsen, Merck; Financial Interests, Personal, Other, Invited speaker Advisory Board: BMS; Financial Interests, Personal, Advisory Board: MSD. C. Morizane: Financial Interests, Personal, Advisory Board: Yakult, MSD, Servier, Boehringer Ingelheim, AstraZeneca, Taiho Pharmaceutical, Merck biopharma; Financial Interests, Personal, Invited Speaker: Novartis, Teijin Pharma; Financial Interests, Institutional, Invited Speaker: Yakult Honsha, Ono Pharmaceutical, Taiho Pharmaceutical, Eisai, MSD K.K., J-Pharma, AstraZeneca, Merck Biopharma; Financial Interests, Institutional, Funding: Daiichi Sankyo RD Novare, Hitachi. J.E. Cundom: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: Boheringer Ingelheim, Astra Zeneca, Takeda, Roche. D. Tougeron: Financial Interests, Personal, Advisory Board: AstraZeneca, Sanofi, Amgen, MSD, Roche, Servier, Servier, Pierre Fabre. F. Dayyani: Financial Interests, Personal, Other, Consulting fees: AstraZeneca, Natera, Exelixis, Genentech; Financial Interests, Personal, Speaker’s Bureau: Deciphera, Eisai, Exelixis, Ipsen, Servier, Natera, Sirtex; Financial Interests, Personal, Other, Contracted research: AstraZeneca, BMS, Taiho, Exelixis, Merck, Trishula, Natera, Ipsen. N. Rokutanda: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. 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.