102P - Potentially prognostic factors of overall survival in advanced biliary tract cancer in the randomised phase III TOPAZ-1 study

Background

In TOPAZ-1 (NCT03875235), durvalumab (D) + gemcitabine and cisplatin (GC) improved overall survival (OS) vs placebo (PBO) + GC in participants with advanced biliary tract cancer (aBTC; primary analysis: hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.66–0.97, p=0.021 [significance threshold p=0.03]) and after a further 6.5 months of follow-up (HR 0.76, 95% CI 0.64–0.91). This exploratory analysis assessed baseline clinical factors for potential prognostic (associated with OS) or predictive (of OS benefit with D + GC) value in TOPAZ-1.

Methods

Potentially prognostic factors were evaluated using Cox proportional hazards models with treatment and each factor. An exploratory adjusted HR for D + GC vs PBO + GC was estimated with a model adjusting for prognostic factors identified by stepwise selection. Unstratified Cox proportional hazards models and interaction tests were performed to assess potential predictive factors. Data cut-off was 25 February 2022.

Results

Potentially prognostic clinical factors are shown (Table). The HR for D + GC vs PBO + GC, adjusted for disease status, primary tumour location, sex, PD-L1, neutrophil to lymphocyte ratio (NLR), cancer antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), liver metastasis, liver involvement (locally advanced or metastatic site in liver/gallbladder), body weight, LDH, albumin and total bilirubin, was 0.70 (95% CI 0.59–0.84). OS HRs for D + GC vs PBO + GC were <1 across assessed clinical (Table) and laboratory factors; no predictive factors for D + GC were found. Table: 102P

IU, initially unresectable; LA, locally advanced; M, metastatic; R, recurrent

Conclusions

Benefit with D + GC was consistent across assessed factors and stable after adjusting for potentially prognostic factors, supporting D + GC as first-line treatment for aBTC.

Clinical trial identification

NCT03875235.

Editorial acknowledgement

Medical writing support, under the direction of the authors, was provided by Elaine Groat, PhD, of CMC Connect, a division of IPG Health Medical Communications, funded by AstraZeneca, in accordance with Good Publication Practice (GPP 2022) guidelines.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

A.R. He: Financial Interests, Personal, Research Grant: AstraZeneca, Genentech, Merck; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Eisai, BMS. M. Bouattour: Financial Interests, Personal, Advisory Board: MSD, BMS, Sirtex Medical, Ipsen, AbbVie, AstraZeneca, Servier, Taiho; Financial Interests, Personal, Invited Speaker: Roche; Non-Financial Interests, Principal Investigator: MSD, BMS, Sirtex Medical, AstraZeneca. V.G. Gupta: Financial Interests, Personal, Stocks/Shares: Zydus Life, RPG Life. L. Evesque: Financial Interests, Personal, Advisory Board: Servier, Amgen, MSD, Merck. D.B. Zhen: Financial Interests, Personal, Advisory Board: QED Therapeutics, Ipsen; Financial Interests, Other, Local PI and Coordinating PI: Merck; Financial Interests, Invited Speaker: TME Pharma, AstraZeneca, Bristol Meyers Squibb, Legend Biotech, Genentech, Cornerstone Pharmaceuticals, Eli Lilly, Seagen, NeoTx Therapeutics, Daiichi Sankyo; Non-Financial Interests, Leadership Role, Binaytara Foundation: Gastrointestinal Oncology Education Chair; Non-Financial Interests, Other, Panel Member of NCCN Neuroendocrine and Adrenal Tumor Guidelines: National Comprehensive Cancer Network. J.O. Park: Financial Interests, Personal, Advisory Board: MedPacto, BMS (Celgene), Servier, MediRama, Adicet Bio, AstraZeneca, Merck Sereno; Financial Interests, Personal, Other, Travel support for a poster presentation at ASCO GI 2023: Minneamrita Therapeutics LLC; Financial Interests, Personal, Research Grant, Clinical research grant: MedPacto, Servier, BMS (Celgene); Financial Interests, Personal, Research Grant: Eutilex, ABL Bio. A. Sookprasert: Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol, Easai, Merck, Roche, Jansen, Pfizer, Novartis. A. Salvatierra: Non-Financial Interests, Personal and Institutional, Principal Investigator: Fundacion Ars Medica. G.M. Vaccaro: Financial Interests, Personal, Speaker’s Bureau: Incyte; Financial Interests, Personal, Advisory Board: AstraZeneca, GSK; Financial Interests, Personal, Advisory Role: Servier. S.A. Ostoich: Non-Financial Interests, Personal, Principal Investigator: Hospital Provincial del Centenario. T. Satoh: Financial Interests, Personal, Invited Speaker, invited speaker and advisory: Ono Pharmaceutical, Daiichi-Sankyo; Financial Interests, Personal, Invited Speaker, Invited speaer and adovisory: Bristol-Myers; Financial Interests, Personal, Invited Speaker, Invited speaker and advisory: Elli-Lilly, Yakult-HOnsha; Financial Interests, Personal, Invited Speaker: Chugai Pharmazeutical, Merck-Biopharm, Takeda, Taiho; Financial Interests, Personal, Advisory Board: Takara-Bio; Financial Interests, Institutional, Invited Speaker: Merck-Biopharm; Financial Interests, Institutional, Invited Speaker, Research Grant and Endosed Department: Ono Pharmaceutical, Chugai Pharmaceutical, Yakult Honsha; Financial Interests, Institutional, Invited Speaker, Research Grant: Bristol-Myers, Elli-Lilly, Daiichi Sankyo, Parexell, Giliad, Taiho, Hutch-Med. M. Żotkiewicz: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. N. Rokutanda: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. H. Kim: Financial Interests, Personal, Full or part-time Employment: 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, MSD; Financial Interests, Institutional, Research Grant: AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, MSD, Handok. All other authors have declared no conflicts of interest.