91P - 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)

Background

In TOPAZ-1 (NCT03875235), D + GC significantly improved overall survival (OS) vs PBO + GC for patients (pts) with advanced BTC (Oh et al. NEJM Evid 2022; https://doi.org/10.1056/EVIDoa2200015). D (immune checkpoint inhibitor) may cause imAEs; imAEs have been associated with improved OS (Zhou et al. BMC Med 2020;18:87).

Methods

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.

Results

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: 91P

^aDays (range; in pts with an imAE)

Conclusions

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 study is warranted.

Clinical trial identification

NCT03875235.

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

AstraZeneca.

Funding

AstraZeneca.

Disclosure

L. Antonuzzo: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Amgen, MSD, BMS; Financial Interests, Institutional, Other, research founding: Novartis. H. Takahashi: Financial Interests, Personal, Other, grant, research support, or honoraria: AstraZeneca, Daiichi Sankyo, Taiho Pharmaceutical, and Yakult. J.O. Park: Financial Interests, Personal, Advisory Board: MedPacto, BMS (Celgene), Servier, MediRama; Financial Interests, Personal, Research Grant, Clinical research grant: MedPacto, Servier, BMS (Celgene). A. Sookprasert: Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol, Eisai, Merck, Roche, Jansen, Pfizer, Norvatis. S. Yang: Financial Interests, Personal, Speaker’s Bureau: AbbVie, Bristol Myers Squibb, Gilead Sciences, Ipsen, Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: AbbVie, Ipsen, Roche. J.E. Cundom: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: Boheringer Ingelheim, AstraZeneca, Takeda, Roche. M. Petrova: Financial Interests, Personal, Invited Speaker: AstraZeneka, EwoPharm, Takeda; Financial Interests, Personal, Advisory Board: Servie, Roche; Non-Financial Interests, Personal, Principal Investigator: AstraZeneka, 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, J. Xiong, K. Heider, 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.