Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster session 13

57P - Immune-mediated adverse event (imAE) incidence, timing and association with efficacy in the phase III TOPAZ-1 study of durvalumab (D) or placebo (PBO) plus gemcitabine and cisplatin (+ GC) in advanced biliary tract cancer (BTC)


10 Sep 2022


Poster session 13



Tumour Site

Hepatobiliary Cancers


Lorenzo Antonuzzo


Annals of Oncology (2022) 33 (suppl_7): S19-S26. 10.1016/annonc/annonc1036


L. Antonuzzo1, H. Takahashi2, J.O. Park3, A. Sookprasert4, R. Gillmore5, S. Yang6, J.E. Cundom7, M. Petrova8, G.M. Vaccaro9, M. Holmblad10, J. Xiong11, K. Heider12, N. Rokutanda10, D. Oh13

Author affiliations

  • 1 Clinical Oncology Unit, Careggi University Hospital, and Department of Experimental and Clinical Medicine, University of Florence, 50139 - Florence/IT
  • 2 Department Of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka/JP
  • 3 Division Of Hematology-oncology, Department Of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul/KR
  • 4 Medical Oncology Unit, Department Of Medicine, Faculty Of Medicine, Khon Kaen University, Khon Kaen/TH
  • 5 Department Of Medical Oncology, Royal Free Hospital, London/GB
  • 6 Division Of Gastroenterology, Department Of Internal Medicine, Taichung Veterans General Hospital, Taichung/TW
  • 7 Department Of Medical Oncology, Instituto de Investigaciones Metabólicas, Buenos Aires/AR
  • 8 Department Of Medical Oncology, MHAT Nadezhda, Sofia/BG
  • 9 Medical Oncology And Hematology-oncology, Providence Cancer Institute, Portland/US
  • 10 Clinical Research, AstraZeneca, Gaithersburg/US
  • 11 Clinical Research, AstraZeneca, Waltham/US
  • 12 Clinical Research, AstraZeneca, Cambridge/GB
  • 13 Division Of Medical Oncology, Department Of Internal Medicine, Seoul National University Hospital, and Cancer Research Institute, Seoul National University College of Medicine, Seoul/KR

Abstract 57P


In TOPAZ-1 (NCT03875235), D + GC significantly improved overall survival (OS) vs PBO + GC for patients (pts) with advanced BTC (Oh et al. J Clin Oncol 2022;40(suppl. 4): Abs 378). D (immune checkpoint inhibitor) may cause imAEs; imAEs have been associated with improved OS (Zhou et al. BMC Med 2020;18:87).


Safety was assessed in pts who received ≥1 dose of study treatment: 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. imAE (AEs of special/possible interest, linked to drug exposure, likely immune-mediated mechanism, no clear alternate aetiology) incidences were calculated by programmatic adjudication. OS hazard ratio (HR) and median OS (mOS) were calculated using the Kaplan-Meier method. Confidence interval (CI) for mOS was derived based on Brookmeyer-Crowley method.


imAEs occurred in more pts in D + GC vs PBO + GC (Table; 1 pt may have >1 imAE). Incidence of Grade 3/4 or serious imAEs was low; median time to onset (mTTO) varied. The most common imAEs (>1% of pts in either arm) were hypothyroid events, dermatitis/rash, hepatic events and adrenal insufficiency (Table). imAEs in D + GC required concomitant treatment more frequently than PBO + GC (Table). imAEs were generally manageable and consistent with the known safety profile. In D + GC, mOS was numerically greater in pts with an imAE of any grade (17.3 months; 95% CI, 12.4–non-calculable]) vs those without (12.6 months; 95% CI, 10.5–13.6; OS HR 0.62; 95% CI, 0.38–0.97). Table: 57P

D + GC (N=338) PBO + GC (N=342)
Any imAE, n (%) 43 (12.7) 16 (4.7)
Grade 3 or 4 8 (2.4) 5 (1.5)
Serious 6 (1.8) 5 (1.5)
With outcome of death 0 1 (0.4)
Leading to treatment discontinuation 3 (0.9) 4 (1.2)
mTTOa 108.0 (1–511) 86.5 (4–533)
Hypothyroid events, n (%) 20 (5.9) 5 (1.5)
mTTOa 111.0 (1–394) 98.0 (43–292)
Dermatitis/rash, n (%) 12 (3.6) 1 (0.3)
mTTOa 71.5 (1–344) 134.0 (134–134)
Hepatic events, n (%) 4 (1.2) 2 (0.6)
mTTOa 90.0 (7–221) 268.5 (4–533)
Adrenal insufficiency, n (%) 4 (1.2) 1 (0.3)
mTTOa 206.0 (86–511) 143.0 (143–143)
Concomitant treatment (%)
Systemic corticosteroids 8.0 3.5
High dose steroids 3.8 2.9
Endocrine therapy 6.5 1.5
Other immunosuppressant 0.3 0.3

aDays (range; in pts with an imAE)


Most imAEs were Grade 1/2 and manageable; imAEs did not increase discontinuation. imAEs occurred at any time during/after treatment; mTTO varied depending on type. Although pt numbers are low, imAEs may be associated with greater OS benefit; further investigation is warranted.

Clinical trial identification


Editorial acknowledgement

Medical writing support, under the direction of the authors, was provided by Elaine Groat, 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





L. Antonuzzo: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Amgen, MSD, BMS; Financial Interests, Institutional, Other, research founding: Novartis. H. Takahashi: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical, Mylan, Yakult, Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, AstraZeneca; Financial Interests, Institutional, Funding: Taiho Pharmaceutical. J.O. Park: Other, Personal, Advisory Board: Roche, AstraZeneca, Bayer; Other, Personal and Institutional, Other, Clinical study: BMS, Ono, Roche, AstraZeneca, MSD, Exelisix; Other, Personal, Other, Co-author: BMS; Other, Personal, Other, Writing engagement: Bayer, Ipsen, Roche, Guerbet. A. Sookprasert: Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol, Eisai, Merck, Roche, Janssen, Pfizer, Novartis. S. Yang: Financial Interests, Personal, Other, Speaker’s Bureau & Advisory Board: AbbVie, Ipsen; Financial Interests, Personal, Speaker’s Bureau: Bristol-Myers Squibb, Gilead Sciences, Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Roche. J.E. Cundom: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, AstraZeneca, Takeda, Roche. M. Petrova: Financial Interests, Personal, Invited Speaker: AstraZeneca, EwoPharm, Takeda; Financial Interests, Personal, Advisory Board: Servier, Roche; Non-Financial Interests, Principal Investigator: AstraZeneca, Sanofi. G.M. Vaccaro: Financial Interests, Personal, Invited Speaker: Incyte; Financial Interests, Personal, Advisory Board: Helsinn Therapeutics, Array Biopharma, Taiho Oncology, Merck Sharp & Dohme Corporation, Exelixis; Financial Interests, Personal, Other, Food and beverage: Eisai. M. Holmblad: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. J. Xiong: Financial Interests, Personal, Stocks/Shares: AstraZeneca. K. Heider: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. N. Rokutanda: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: 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; Financial Interests, Institutional, Research Grant: AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, MSD, Handok. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.