78P - Updated overall survival (OS) from the phase III TOPAZ-1 study of durvalumab (D) or placebo (PBO) plus gemcitabine and cisplatin (+ GC) in patients (pts) with advanced biliary tract cancer (BTC)

Background

Advanced BTC is a rare, heterogenous cancer with poor prognosis. At the preplanned interim analysis (data cutoff 11 August 2021) of TOPAZ-1 (NCT03875235), D + GC significantly improved OS versus PBO + GC in pts with advanced BTC (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.66–0.97; p=0.021). We report an updated OS and safety analysis for TOPAZ-1.

Methods

Pts previously untreated for unresectable locally advanced, recurrent or metastatic BTC were randomised 1:1 to receive D (1500 mg every 3 weeks [Q3W]) or PBO + G (1000 mg/m²) and C (25 mg/m²) on days 1 and 8 Q3W, for up to 8 cycles, followed by D (1500 mg Q4W) or PBO monotherapy until disease progression or unacceptable toxicity. The primary objective was to assess OS. This OS and safety analysis was conducted after 6 months (mo) of additional follow-up with 76.9% overall OS event maturity.

Results

At data cutoff (25 February 2022), 685 pts were randomised to D + GC (n=341) or PBO + GC (n=344); median (95% CI) follow-up time was 23.4 (20.6–25.2) mo and 22.4 (21.4–23.8) mo, respectively. Median (95% CI) OS was 12.9 (11.6–14.1) mo with D + GC and 11.3 (10.1–12.5) mo with PBO + GC (HR, 0.76; 95% CI, 0.64–0.91). OS HRs (95% CI) favoured D + GC in all prespecified subgroups, including disease status (initially unresectable, 0.79 [0.65–0.95]; recurrent, 0.76 [0.49–1.20]), primary tumour location (intrahepatic cholangiocarcinoma, 0.78 [0.62–0.99]; extrahepatic cholangiocarcinoma, 0.61 [0.41–0.91]; gallbladder cancer, 0.90 [0.64–1.25]) and PD-L1 (tumour area positivity [TAP] ≥1%, 0.75 [0.60–0.93]; TAP <1%, 0.79 [0.58–1.09]). OS rates (D + GC vs PBO + GC) at 12 mo, 18 mo and 24 mo were 54.3% vs 47.1%, 34.8% vs 24.1% and 23.6% vs 11.5%, respectively. Grade 3/4 treatment-related adverse events (TRAEs) occurred in 60.9% of pts receiving D and 63.5% of pts receiving PBO; TRAEs leading to discontinuation of any study medication occurred in 8.9% and 11.4% of pts, respectively.

Conclusions

D + GC continues to demonstrate clinically meaningful benefit vs PBO, which is consistent among subgroups, and manageable safety with longer follow-up, further supporting D + GC as a new first-line standard of care regimen for pts with advanced BTC.

Clinical trial identification

NCT03875235.

Editorial acknowledgement

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

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

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. A.R. He: Financial Interests, Personal, Research Grant: Genentech and Merck; Financial Interests, Personal, Other, Consultant Fee: AstraZeneca, Bristol Myers Squibb, and Genentech/Roche; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb and Eisai. L. Chen: Financial Interests, Personal, Invited Speaker: PharmaEngine (TW), Ono, BMS, Eli Lilly, Ipsen, Novartis, TTY (TW), C-Stone (TW); Financial Interests, Personal, Other, Medical Monitoring for clinical trial.: Taivex (TW); Financial Interests, Personal, Other, DSMC member for clinical trials.: OBI (TW); Financial Interests, Personal, Advisory Board: MSD, Astra Zeneca, SynCore (TW); Financial Interests, Personal, Full or part-time Employment, Co-affiliated, Distinguished Investigator and Senior Physician Staff: National Institute of Cancer Research, National Health Research Institutes, Taiwan; Financial Interests, Personal, Full or part-time Employment, Professor of Internal Medicine: Kaohsiung Medical Univrsity Hopsital, Kaohsiung Medical University, Kaohsiung, Taiwan; Financial Interests, Personal, Invited Speaker, Independent Director: ScinoPharm Taiwan, Ltd.; Financial Interests, Personal, Invited Speaker, Alpha-enolase specific antibodies: HuniLife Biotechnology, Inc., Taiwan; Financial Interests, Personal, Invited Speaker, TOPAZ-1, phase III trial: AstraZeneca; Financial Interests, Personal, Invited Speaker, ATTRACTIONs trials, ATT-2 (3L), ATT-4 (1L), ATT-5 (Adjuvant) and ATT-6 (1L).: Ono; Financial Interests, Personal, Invited Speaker, SynCore CT4006, phase 3 trial: Syncore BioPharma, Taiwan; Financial Interests, Institutional, Invited Speaker, Research funding and study medication for TCOG IIT.: Celgene; Financial Interests, Institutional, Invited Speaker, Industry-sponsored, phase 2 bridging trial in TCOG.: TTY, Taiwan; Non-Financial Interests, Personal, Principal Investigator, Investigator-initiated trials: Taiwan Cooperative Oncology Group, National Institute of Cancer Research, Taiwan; Non-Financial Interests, Personal, Invited Speaker, Managing Director: Taiwan Oncology Society, taiwan; Non-Financial Interests, Personal, Leadership Role, President (2021.09 ∼): Taiwan NeuroEndocrine Tumor Society (TNETS); Non-Financial Interests, Personal, Invited Speaker: Taiwan Pancreas Society, Taiwan; Non-Financial Interests, Institutional, Product Samples, Medication support for TCOG trial.: Syncore BioPharma, Taiwan; Non-Financial Interests, Institutional, Product Samples, Medication for TCOG trials.: TTY; Non-Financial Interests, Institutional, Product Samples, Targeted Cancer Panel NGS testing.: ACTgenomics (TW). 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. A. Vogel: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, Boston Scientific, Boehringer Mannheim, Eisai, Incyte, Ipsen, MSD, Pierre Fabre, Roche, Servier, Sirtex; Financial Interests, Personal, Invited Speaker: BMS, Eisai, Incyte, Ipsen, Imaging Equipment Ltd. (AAA), MSD, Roche, MSD, Beigene, Jiangsu Hengrui Medicines. J.W. Kim: Financial Interests, Personal, Research Grant: Inno.N and Jeil Pharm; Financial Interests, Personal, Other, Consultant Fee: AstraZeneca, BeiGene, Beyond Bio, Bristol Myers Squibb/Celgene, Eisai, GC Cell, MSD, ONO, Sanofi-Aventis, Servier, and TCUBEit. T. Suksombooncharoen: Financial Interests, Personal, Invited Speaker: Astrazeneca, Novartis, Bayer, Bristol Myers Squibb, baxter, MUNDIPHARMA (THAILAND), Roche, Eli Lilly, Takeda, MSD, Amgen, Janssen; Financial Interests, Personal, Advisory Board: Roche, Novartis; Non-Financial Interests, Personal, Principal Investigator: Astrazenaca, Novartis, Roche, MSD. M. Kitano: Financial Interests, Personal, Research Grant: AbbVie and Takeda Pharmaceutical; Financial Interests, Personal, Other, Honoraria: EA Pharma. H.A. Burris: Financial Interests, Personal, Research Grant: AbbVie, Agios, Arch, ARMO Biosciences, Array BioPharma, Arvinas, AstraZeneca, Bayer, BIND Therapeutics, BioAtla, BioMed Valley, BioTheryx, Boehringer Ingelheim, Bristol Myers Squibb, CALGB, CicloMed, Coordination Pharmaceuticals, CytomX, eFFECTOR Therapeu; Financial Interests, Personal, Other, Consultant Fee: AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, FORMA Therapeutics, GRAIL, Incyte, Novartis, Pfizer, and Vincerx. M. Bouattour: Financial Interests, Personal, Other, Consultant Fee: AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, Ipsen, MSD, Roche, and Sirtex Medical. S. Tanasanvimon: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, MSD, Novartis, and Roche. R.E. Zaucha: Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bristol Myers Squibb, Eisai, Ipsen, and Roche. A. Avallone: Financial Interests, Personal, Research Grant: Amgen, Bayer, and Bristol Myers Squibb; Financial Interests, Personal, Other, Consultant Fee: Amgen, Eisai, and MSD; Financial Interests, Personal, Other, Honoraria: Amgen, AstraZeneca, MSD, and Servier. J.E. Cundom: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: Boheringer Ingelheim, Astra Zeneca, Takeda, Roche. N. Rokutanda: Financial Interests, Personal, Full or part-time Employment: AstraZenea; Financial Interests, Personal, Stocks/Shares: AstraZenea. M. Watras: Financial Interests, Personal, Full or part-time Employment, I am a full time employee of AstraZeneca Poland.: 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. J.W. Valle: Financial Interests, Personal, Advisory Board: AstraZeneca, 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. All other authors have declared no conflicts of interest.