Comparative efficacy and safety of tislelizumab versus anti-PD-1 treatments in second-line esophageal squamous cell carcinoma: Simulated treatment comparisons

BackgroundTislelizumab has demonstrated survival benefit over chemotherapy in previously treated advanced esophageal squamous cell carcinoma (ESCC) in an open-label phase 3 study (RATIONALE 302, N=512, NCT03430843). In the absence of head-to-head studies, anchored simulated treatment comparisons (STCs) estimated the relative effect of tislelizumab versus other anti-PD-1 treatments approved in the European Union and United Kingdom.MethodsIndividual patient data from RATIONALE 302 were adjusted to aggregate data in each comparator study using STC. Clinical expert input, statistical analyses and literature searches determined important effect modifiers. Depending on data availability, STCs for overall survival (OS) and progression-free survival (PFS) were adjusted for Eastern Cooperative Oncology Group performance status (ECOG-PS), disease status, PD-1 expression status, liver and lung metastasis; whereas STC for treatment-related adverse event (TRAE) grade ≥ 3 analysis was adjusted for age, ECOG-PS, PD-1 expression, liver metastasis, and previous therapies. Additional sensitivity analyses along with subgroup analyses (PD-1 category and baseline ECOG-PS) were considered. These analyses were also conducted using the latest DCO (Dec 28, 2022).ResultsComparator studies were similar to RATIONALE 302 with comparable control arms. After adjustment, no significant differences were estimated in PFS, OS, or TRAEs between tislelizumab and anti-PD-1 comparators (Table). Results from sensitivity, subgroup and latest DCO aligned with the base case. Table: 1417P Population-adjusted relative effects in the base case Tislelizumab (RATIONALE 302) versus comparator (study) OS PFS TRAE grade ≥3 HR (95% CI) HR (95% CI) OR (95% CI) Nivolumab (ATTRACTION-3) 0.88 (0.65, 1.19) 0.79 (0.59, 1.07) 1.30 (0.68, 2.48) Pembrolizumab (KEYNOTE-181) 0.94 (0.67, 1.32) 0.95 (0.63, 1.43) Not feasible* CI, Confidence Interval; HR, Hazard ratio; OR, Odds ratio. *TRAE data was not available for pembrolizumab. DCO=Dec 01, 2020 ConclusionsThe STCs showed comparable efficacy and safety between tislelizumab, pembrolizumab, and nivolumab.Clinical trial identificationNCT03430843.Editorial acknowledgementEditorial support, under the direction of the authors, was provided by Smitha Reddy, PhD, of Envision Pharma Inc.Legal entity responsible for the studyBeiGene, Ltd.FundingBeiGene, Ltd.DisclosureE.C. Smyth: Financial Interests, Personal, Invited Speaker: Amgen, Bristol Myers Squibb, Imedex, Merck, Novartis, Prova Education, Servier, TouchIME, Elsevier, Peervoice, Cor2Ed, Daiichi Sankyo, MSD, Suzhou Liangihui Network Technology Company Ltd. Financial Interests, Personal, Other, TSC: Amgen; Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, Bristol Myers Squibb, Bristol Myers Squibb, My Personal Therapeutics, Novartis, Roche, Servier, Zymeworks, Viracta, Boehringer Ingelheim, AbbVie, Natera; Financial Interests, Personal, Other, IDMC: BeiGene, Zymeworks; Financial Interests, Personal, Other, IDMC chair: Everest Clinical Research; Financial Interests, Personal, Other, IDMC Chair: Jazz Pharmaceuticals; Financial Interests, Personal, Officer: EORTC GI Clinical Trials Group; Financial Interests, Institutional, Local PI: Daiichi Sankyo, Merus, Basilea, MSD, Mirati; Financial Interests, Institutional, Coordinating PI: Roche, AstraZeneca, Amgen; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, AstraZeneca; Non-Financial Interests, Leadership Role, Trustee: UK & Ireland Oesophagogastric Group (UKIOG). J.A. Ajani: Financial Interests, Personal, Advisory Board: BMS, Gilead, Astellas, AZ, Jazz, KirinKyowa, Servier, BeiGene, Daiichi Sankyo; Financial Interests, Institutional, Coordinating PI, My institution receives funding: BMS; Financial Interests, Institutional, Coordinating PI: Merck, Jazz, Astellas, Delta Fly, Gilead, Roche. K. Wang: Financial Interests, Personal, Full or part-time Employment: BeiGene; Financial Interests, Personal, Stocks or ownership: BeiGene. J. Coaquira Castro: Financial Interests, Personal, Other, Travel: BeiGene; Financial Interests, Personal, Stocks or ownership: BeiGene, Jazz Pharmaceuticals. M. Figueiredo: Financial Interests, Personal, Speaker, Consultant, Advisor: Pfizer; Financial Interests, Personal, Invited Speaker: Pfizer. K. Soulanis, A. Tasoulas, G. Nikolaidis: Financial Interests, Personal, Full or part-time Employment: IQVIA. E. Priedane: Financial Interests, Personal, Full or part-time Employment: BeiGene. L. Zhan: Financial Interests, Personal, Full or part-time Employment: BeiGene; Financial Interests, Personal, Stocks or ownership: BeiGene; Financial Interests, Personal, Other, Travel: BeiGene. All other authors have declared no conflicts of interest.