135P - Three-year survival, safety and extended long-term survivor (eLTS) analysis from the phase III TOPAZ-1 study of durvalumab (D) plus chemotherapy in advanced biliary tract cancer (aBTC)

Background

At primary analysis, the TOPAZ-1 study (NCT03875235), D + gemcitabine + cisplatin (GC) significantly improved overall survival (OS), vs placebo (P)+GC, with manageable safety, in aBTC. We report an updated 3-year OS, eLTS and safety analysis.

Methods

Participants (pts) received D+GC or P+GC every 3 weeks (Q3W), followed by D or P monotherapy Q4W. OS and serious adverse events (SAEs) were assessed ∼36 mo after the last pt was randomised (DCO: 23 Oct 2023). Characteristics and outcomes were assessed in eLTS (full analysis set [FAS] pts who survived ≥30 mo after randomisation).

Results

Overall, 685 pts were randomised to D+GC (n=341) or P+GC (n=344). After median (95% CI) follow-up of 41.3 (39.3–44.1) mo, median OS (mOS; 95% CI) was 12.9 (11.6–14.1) mo for D+GC and 11.3 (10.1–12.5) mo for P+GC (HR, 0.74; 95% CI, 0.63–0.87). The 36-mo OS rate was 14.6% for D+GC vs 6.9% for P+GC. In pts who achieved disease control, the 36-mo OS rate was 17.0% for D+GC vs 7.6% for P+GC. In the FAS, 88/685 (12.8%) pts were eLTS, with more eLTS in D+GC (58/341 [17.0%]) than in P+GC (30/344 [8.7%]; Table). All clinically relevant subgroups were present in eLTS (Table). A higher proportion of eLTS achieved an objective response than in the FAS. Around 1 in 3 (32/91) pts who responded to D were eLTS. A higher proportion of eLTS in P+GC received subsequent therapy, including immunotherapy, than in D+GC. SAEs were comparable between arms for eLTS (D+GC: 32.8%; P+GC: 36.7%), and less frequent than in the FAS (D+GC: 48.8%; P+GC: 44.4%). Table: 135P

*Complete or partial response by RECIST v1.1.RECIST, Response Evaluation Criteria in Solid Tumors.

Conclusions

After 3-years of follow-up, D+GC continued to demonstrate clinically meaningful long-term survival benefit; further improved in pts who achieved disease control. All clinically relevant subgroups were present in eLTS, further supporting standard of care status for D+GC in pts with aBTC. Previously presented at ESMO GI 2024, FPN: 279MO, Do-Youn Oh et al. Reused with permission.

Clinical trial identification

NCT03875235.

Editorial acknowledgement

Medical writing support, under the direction of the authors, was provided by Andrea Hough, PhD, CMC Connect, a division of IPG Health Medical Communications, and was funded by AstraZeneca.

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, MSD, LG Chem, Astellas, AbbVie, J-Pharma, Mirati Therapeutics, Eutilex, Moderna, Idience, Alligator Bioscience AB; Financial Interests, Institutional, Research Grant: AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, MSD, Handok. A.R. He: Financial Interests, Personal, Invited Speaker, Speaker's Bureau: Eisai; Financial Interests, Personal, Invited Speaker, Speaker's bureau: AstraZeneca; Financial Interests, Institutional, Research Grant: AstraZeneca. L. Chen: Financial Interests, Personal, Invited Speaker: PharmaEngine (TW), ONO, BMS, Ipsen, Novartis, TTY (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, AstraZeneca; Financial Interests, Personal, Advisory Board, Scientific Advisory Committee: ScinoPharm Taiwan, Onward; 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 University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Financial Interests, Personal, Member of Board of Directors, Independent Director: ScinoPharm Taiwan, Ltd.; Financial Interests, Personal, Advisory Board, Alpha-enolase specific antibodies: HuniLife Biotechnology, Inc., Taiwan; Financial Interests, Personal, Steering Committee Member, TOPAZ-1, phase III trial: AstraZeneca; Financial Interests, Personal, Steering Committee Member, ATTRACTIONs trials, ATT-2 (3L), ATT-4 (1L), ATT-5 (Adjuvant) and ATT-6 (1L): ONO; Financial Interests, Personal, Trial Chair, SynCore CT4006, phase III trial: Syncore BioPharma, Taiwan; Financial Interests, Institutional, Trial Chair, Industry-sponsored, phase II bridging trial in TCOG: TTY, Taiwan; Financial Interests, Institutional, Steering Committee Member, C3651003 (Cancer cachexia), Operations steering Committee, country lead: Pfizer; Non-Financial Interests, Personal, Principal Investigator, Investigator-initiated trials: Taiwan Cooperative Oncology Group, National Institute of Cancer Research, Taiwan; Non-Financial Interests, Personal, Leadership Role, President (2021.09 ∼): Taiwan NeuroEndocrine Tumor Society (TNETS); Non-Financial Interests, Personal, Member of Board of Directors: Taiwan Pancreas Society, 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); Non-Financial Interests, Personal, Other, International Staring Committee Member (ISCM), Academic Planning Committee, JSMO: Japanese Society of Medical Oncology (JSMO); Non-Financial Interests, Personal, Leadership Role, Council Member: Asian Oncology Society (AOS). T. Okusaka: Financial Interests, Personal, Advisory Board: Eisai, Nihon Servier, AstraZeneca, FUJIFILM Toyama Chemical; Financial Interests, Personal, Invited Speaker: AstraZeneca, Eisai, Chugai Pharma, Nihon Servier, Incyte, Novartis, Daiichi Sankyo, Taiho, Yakult, Myriad Genetics, Kyowa Kirin, Ono; Financial Interests, Institutional, Local PI: AstraZeneca, Eisai, Bristol Myers Squibb, Incyte, Syneos Health, Chiome Bioscience, Sysmex. A. Vogel: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Boehringer Mannheim, Eisai, Incyte, Ipsen, MSD, Roche, Servier, Tyra, Taiho, AbbVie; Financial Interests, Personal, Invited Speaker: BMS, Eisai, Ipsen, MSD, Roche, AstraZeneca; Financial Interests, Personal, Steering Committee Member: Roche, MSD, Beigene, Boehringer-Ingelheim. 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: AstraZeneca, Novartis, Roche, MSD. M. Kitano: Financial Interests, Personal, Invited Speaker, Fee for lecture: AstraZeneca; Financial Interests, Institutional, Funding, Funding for Clinical Trial: AstraZeneca. H.A. Burris: Financial Interests, Institutional, Other, Consulting: AstraZeneca, GRAIL, Incyte, Roche, Vincerx Pharma; Financial Interests, Personal, Stocks/Shares: HCA Healthcare; Financial Interests, Institutional, Local PI: AbbVie, Agios, Arch Oncology, ARMO Biosciences, Array BioPharma, Arvinas, AstraZeneca, Bayer, BeiGene, BioAtla, Boehringer Ingelheim, Bristol Myers Squibb, CALGB, Coordination Pharmaceuticals, CytomX, Lilly, EMD Serono, Roche/Genentech, Gossamer Bio, Harpoon Therapeutics, Hengrui Therapeutics, Incyte, Jounce Therapeutics, Kymab, MacroGenics, MedImmune, Merck, Millennium/Takeda, Moderna, NGM Biopharmaceuticals, Novartis, Pfizer, Revolution Medicines, Ryvu Therapeutics, Foundation Medicine, Seagen, Tesaro, TG Therapeutics, Verastem, Vertex Pharmaceuticals, XBiotech, Zymeworks; Financial Interests, Institutional, Funding: Celgene; Non-Financial Interests, Personal, Other, Consulting: Bristol Myers Squibb, Novartis. 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, Personal, Principal Investigator: MSD, BMS, Sirtex Medical, AstraZeneca. S. Tanasanvimon: Financial Interests, Personal, Invited Speaker: Ipsen, Roche, BMS, Eisai, Amgen, MSD, Merck, Pfizer, Novartis; Financial Interests, Personal and Institutional, Local PI: MSD, Roche, Amgen, AstraZeneca. R.E. Zaucha: Financial Interests, Personal, Invited Speaker: BMS, Novartis, MSD; Financial Interests, Personal, Writing Engagement: Ipsen, AstraZeneca, Janssen; Non-Financial Interests, Personal, Principal Investigator: BMS, AstraZeneca, Ipsen, Roche, Janssen. A. Avallone: Financial Interests, Institutional, Research Grant: Amgen, Bayer, Bristol-Myers; Financial Interests, Personal, Advisory Board: MSD, Amgen, Eisai, Astra-Zeneca. J.E. Cundom: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: Boehringer-Ingelheim, AstraZeneca, Takeda, Roche. A. Kuzko: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. J. Wang, I. Xynos: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: 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. All other authors have declared no conflicts of interest.