55P - Subsequent anticancer therapy (SAT) analysis from 3-year follow-up of the phase III TOPAZ-1 study of durvalumab plus gemcitabine and cisplatin in biliary tract cancer (BTC)

Background

In TOPAZ-1 (NCT03875235), durvalumab plus gemcitabine and cisplatin (D+GC) demonstrated statistically significant and clinically meaningful overall survival (OS) benefit vs placebo (P)+GC in participants (pts) with advanced BTC (OS hazard ratio [HR; 95% confidence interval (CI)], 0.80 [0.66–0.97]), with benefits persisting at 3-year (3-yr) follow-up (0.74 [0.63–0.87]). Here, we report an analysis of SAT use at the 3-yr follow-up.

Methods

Pts with recurrent or previously untreated unresectable, locally advanced or metastatic BTC received D (1500 mg) or P plus G (1000 mg/m²) and C (25 mg/m²), every 3 weeks for up to 8 cycles, followed by D or P monotherapy every 4 weeks. SAT use and OS are reported ∼36 months (mo) after the last pt was randomised (data cut-off: 23 October 2023).

Results

Of 685 pts randomised, 54.8% (187/341) of pts in D+GC and 54.9% (189/344) of pts in P+GC received SAT (Table). Immunotherapy as SAT was numerically higher in P+GC than D+GC at 3 yrs (Table). OS HRs favoured D+GC vs P+GC in pts with SAT use (OS HR [95% CI], 0.80 [0.65–1.00]) and without SAT use (0.73 [0.58–0.93]). Median OS was longer in pts with SAT use vs without SAT use, regardless of treatment (Table). OS rates at 24 and 36 mo were higher in D+GC vs P+GC, regardless of SAT use (Table). In the full analysis set (FAS), OS benefit with D+GC was consistent after censoring pts at initiation of immunotherapy or targeted therapy (Table). D+GC did not appear to negatively impact the efficacy of targeted SAT, though data are limited. Median (95% CI) time to first SAT was longer in D+GC (10.81 [9.86–12.20] mo) than P+GC (9.72 [8.90–10.30] mo; HR, 0.75; 95% CI, 0.60–0.92). Table: 55P

*FGFR, IDH1, HER2, VEGF, DDR and other. ^†1 pt had unknown SAT.

Conclusions

After 3 yrs’ follow-up, OS was improved with D+GC vs P+GC, regardless of SAT use. Despite higher use of immunotherapy as SAT in P+GC vs D+GC at 3 yrs, the OS HR for D+GC vs P+GC was consistent with the primary analysis. These results further support D+GC as standard of care for 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, funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

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; Financial Interests, Personal, Steering Committee Member: Roche, MSD, BeiGene, Jiangsu Hengrui Medicines. 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, 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, Other, Consultant: AstraZeneca, MSD, National Institute of Cancer Research, Ono Pharma, SynCore (TW), Taivex (TW) and Taiwan Cooperative Oncology Group; Financial Interests, Personal, Full or part-time Employment: Kaohsiung Medical University Hospital and National Institute of Cancer Research; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb, C-Stone (TW), Eli Lilly, Ipsen, Novartis, Ono Pharma, Pharma Engine (TW) and TTY (TW). 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. T. Suksombooncharoen: Financial Interests, Personal, Other, Speaker fees: Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Baxter, Eli Lilly, Mundipharma (Thailand), Janssen, MSD, Novartis, Roche, and Takeda; Financial Interests, Personal, Other, Advisory fees: Novartis and Roche. 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, 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, 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, Principal Investigator: BMS, AstraZeneca, Ipsen, Roche, Janssen. A. Avallone: Financial Interests, Institutional, Research Grant: Amgen, Bayer, Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: MSD, Amgen, Eisai, AstraZeneca. J.E. Cundom: Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, Takeda, AstraZeneca, Roche; Financial Interests, Personal, Advisory Board: MSD. 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: 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.