Tislelizumab (TIS) versus sorafenib (SOR) in first-line (1L) treatment of unresectable hepatocellular carcinoma (HCC): The RATIONALE-301 European/North American (EU/NA) subgroup.

Arndt Vogel Hannover Medical School, Hannover, Germany info_outline Arndt Vogel, Tim Meyer, Eric Assenat, Mariona Calvo Campos, Songzi Li, Yaxi Chen, Frederic Boisserie, Ramil Abdrashitov, Donatella Marino, Richard S. Finn

Authors Arndt Vogel Hannover Medical School, Hannover, Germany info_outline Arndt Vogel, Tim Meyer, Eric Assenat, Mariona Calvo Campos, Songzi Li, Yaxi Chen, Frederic Boisserie, Ramil Abdrashitov, Donatella Marino, Richard S. Finn Organizations Hannover Medical School, Hannover, Germany, Royal Free Hospital NHS Trust, London, United Kingdom, Montpellier University Hospital, Montpellier, France, Institut Català d'Oncologia, Hospital Duran i Reynals and IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain, BeiGene (Ridgefield Park) Co., Ltd., Ridgefield Park, NJ, BeiGene (Beijing) Co., Ltd., Beijing, China, BeiGene Co., Ltd., Fulton, MD, Ordine Mauriziano Hospital, Turin, Italy, University of California Los Angeles, Los Angeles, CA Abstract Disclosures Research Funding Pharmaceutical/Biotech Company BeiGene, Ltd., This study was sponsored by BeiGene, Ltd. Medical writing support, under the direction of the authors, was provided by Adeline Lum Nde, PhD, of Ashfield MedComms, an Inizio company, and was funded by BeiGene, Ltd Background: HCC is one of the most commonly diagnosed cancers globally. Most cases occur in Asia, although a number of patients (pts) are affected in Europe and North America. In the phase 3, open-label RATIONALE-301 trial (NCT03412773), TIS, a PD-1 inhibitor, showed non-inferior overall survival (OS) versus SOR (hazard ratio 0.85, 95% CI: 0.71, 1.02), and a favorable safety profile, in 1L treatment of pts with unresectable HCC. Here, efficacy and safety of TIS versus SOR in the RATIONALE-301 EU/NA subgroup were compared with the overall population (OP). Methods: Systemic therapy-naïve adults with histologically confirmed HCC were randomized (1:1) to receive TIS (200 mg IV Q3W) or SOR (400 mg orally BID) until disease progression, intolerable toxicity, or withdrawal. The primary endpoint was OS; secondary endpoints included objective response rate (ORR), progression-free survival (PFS), and duration of response (DoR) by blinded independent review committee per RECIST v1.1, and safety. Results: In the EU/NA subgroup (172/674 pts randomized), at data cutoff (July 11, 2022), median (m) OS follow-up was 37.9 months (mo) (TIS) vs 38.5 mo (SOR). At baseline, fewer pts in the EU/NA subgroup had Barcelona Clinic Liver Cancer (BCLC) Stage C disease (70% vs 78%) and extrahepatic spread (51% vs 62%), and more had a non-viral etiology (60% vs 24%) or underlying HCV infection (28% vs 13%) than in the OP, respectively. Distribution of other baseline characteristics was generally similar between the EU/NA subgroup and the OP. Efficacy data in the EU/NA subgroup were consistent with the OP. Numerically longer mOS and mDoR, higher ORR, and similar mPFS were observed with TIS versus SOR in the EU/NA subgroup. In the EU/NA safety population, incidence of ≥grade 3 treatment-emergent adverse events (TEAEs; 46% vs 66%), ≥grade 3 treatment-related TEAEs (TRAEs; 17% vs 50%), and TRAEs leading to discontinuation (9% vs 15%) was lower with TIS versus SOR, respectively, similar to the OP. Conclusions: In the RATIONALE-301 EU/NA subgroup, mOS of TIS was non-inferior versus SOR, consistent with the findings from the OP. Numerically longer mOS and mDoR, and a higher ORR was seen with TIS versus SOR in the EU/NA subgroup, which had a higher rate of pts with non-viral etiology and a slightly lower number of pts with advanced-stage disease (BCLC Stage C) compared with the OP. Clinical trial information: NCT03412773. EU/NA subgroup OP TIS (n=89) SOR (n=83) TIS (n=342) SOR (n=332) mOS, mo (95% CI) 18.3 (11.0, 26.6) 13.7 (8.5, 19.0) 15.9 (13.2, 19.7) 14.1 (12.6, 17.4) ORR, % (95% CI) 19.1 (11.5, 28.8) 2.4 (0.3, 8.4) 14.3 (10.8, 18.5) 5.4 (3.2, 8.4) mDoR, mo (95% CI) 36.1 (10.1, NE) 9.1 (5.5, NE) 36.1 (16.8, NE) 11.0 (6.2, 14.7) mPFS, mo (95% CI) 3.7 (2.2, 4.3) 3.9 (2.2, 6.1) 2.1 (2.1, 3.5) 3.6 (2.2, 4.1) Intent-to-treat analysis set; data cutoff: July 11, 2022. CI, confidence interval; NE, not evaluable.

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