279MO - Three-year survival, safety and extended long-term survivor (eLTS) analysis from the phase III TOPAZ-1 study of durvalumab (D) plus chemotherapy in biliary tract cancer (BTC)

Background

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

Methods

Participants (pts) with advanced BTC received D or PBO+GC every three weeks (Q3W), followed by D or PBO 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 (pts in the full analysis set [FAS] who survived ≥30 mo after randomisation).

Results

Overall, 685 pts were randomised to D+GC (n=341) or PBO+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 PBO+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 PBO+GC. In pts who achieved disease control, the 36-mo OS rate was 17.0% for D+GC vs 7.6% for PBO+GC. In the FAS, 88/685 (12.8%) pts were eLTS, with more eLTS in D+GC (58/341 [17.0%]) than in PBO+GC (30/344 [8.7%]; Table). All clinically relevant subgroups were represented in eLTS (Table). A higher proportion of eLTS achieved an objective response than in the FAS. Approximately 1 in 3 (32/91) pts who responded to D were eLTS. A higher proportion of eLTS in PBO+GC received subsequent therapy, including immunotherapy, than in D+GC. SAEs were comparable between arms for eLTS (D+GC: 32.8%; PBO+GC: 36.7%), and less frequent than in the FAS (D+GC: 48.8%; PBO+GC: 44.4%). Table: 279MO

∗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 that was further improved in pts who achieved disease control. All clinically relevant subgroups were represented in eLTS, further supporting standard of care status for D+GC in diverse pts with advanced BTC.

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; Financial Interests, Institutional, Research Grant: AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, MSD, Handok. A.R. He: Financial Interests, Personal, Research Grant: AstraZeneca, Genentech, Merck; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Eisai, BMS. 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, Invited Speaker: 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, Janssen, MSD, Pierre Fabre, Roche, Servier, Tyra, Tahio; Financial Interests, Personal, Invited Speaker: BMS, Eisai, Ipsen, Lilly, MSD, Roche, AstraZeneca, Roche, MSD, BeiGene, Jiangsu Hengrui Medicines. J.W. Kim: Financial Interests, Personal, Research Grant: inno.N, Jeil Pharm; Financial Interests, Personal, Other, Consulting fees: AstraZeneca, BeiGene, Beyond Bio, Bristol Myers Squibb/Celgene, Eisai, GC Cell, MSD, ONO, Sanofi-Aventis, Servier, and TCUBEit. T. Suksombooncharoen: Financial Interests, Personal, Other, Consulting fees: AstraZeneca, Novartis, Roche/Genentech; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Baxter, Bayer, Bristol Myers Squibb, Janssen, Lilly, MSD, Novartis, Pfizer, Takeda Pharmaceutical. M. Kitano: Financial Interests, Personal, Research Grant: AbbVie Takeda Pharmaceutical; Financial Interests, Personal, Other, Honoraria: EA Pharma. H.A. Burris: Financial Interests, Institutional, Other, Consulting: AstraZeneca, GRAIL, Incyte, Roche, Vincerx Pharma; Financial Interests, Personal, Stocks/Shares: HCA Healthcare; Financial Interests, Institutional, Invited Speaker: AbbVie, Agios, Arch Oncology, ARMO Biosciences, Array BioPharma, Arvinas, AstraZeneca, Bayer, BeiGene, BioAtla, BioMed Valley Discoveries, BioTheryX, Boehringer Ingelheim, Bristol Myers Squibb, CALGB, CicloMed, Coordination Pharmaceuticals, CytomX, eFFECTOR Therapeutics, Lilly, EMD Serono, Roche/Genentech, Gilead Sciences, GSK, Gossamer Bio, Harpoon Therapeutics, Hengrui Therapeutics, Incyte, Janssen, 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, 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, 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, Invited Speaker: MSD, Roche, Amgen, AstraZeneca. R.E. Zaucha: Financial Interests, Personal, Invited Speaker: BMS, Novartis, Ipsen, MSD, AstraZeneca, janssen; Non-Financial Interests, 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, AstraZeneca. 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, Invited Speaker: Incyte, Ipsen, and Mylan; Financial Interests, Personal, Advisory Board: Agios, AstraZeneca, Autem, Baxter, Hutchinson Medipharma, Image Equipment Ltd., NuCana BioMed, QED, Sirtex, Servier, and Zymeworks. All other authors have declared no conflicts of interest.