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Randomized, phase 3 study of tislelizumab versus sorafenib as first-line treatment for unresectable hepatocellular carcinoma (HCC): RATIONALE-301 age ≥65 years subgroup
HCC is one of the most commonly diagnosed cancers globally, with an increasing number of patients affected in the ≥65 years age group. In the phase 3, open-label RATIONALE-301 trial (NCT03412773), tislelizumab, a PD-1 inhibitor, showed non-inferior overall survival (OS) vs sorafenib (hazard ratio 0.85, 95% confidence interval [CI]: 0.71, 1.02) and a favorable safety profile in first-line treatment of patients with unresectable HCC. Here, we present results from the subgroup of patients aged ≥65 years in RATIONALE-301.
Systemic therapy-naïve adults with histologically confirmed HCC (Barcelona Clinic Liver Cancer [BCLC] Stage C or Stage B that was not amenable to/progressed after loco-regional therapy, Child-Pugh A), with ≥1 measurable lesion (RECIST v1.1) and an ECOG PS ≤1 were randomized (1:1) to tislelizumab (200 mg intravenously every 3 weeks) or sorafenib (400 mg orally twice daily) until disease progression, intolerable toxicity, or withdrawal. The primary endpoint was OS; secondary endpoints included objective response rate (ORR) and progression-free survival (PFS) by blinded independent review committee, and safety.
In total, 255 of the 674 randomized patients were in the ≥65 years subgroup (tislelizumab: n=134, sorafenib: n=121), with median (m) age of 71.0 years (range 65-86). At data cutoff (July 11, 2022), median survival follow-up was 38.9 months in the tislelizumab arm vs 39.9 months in the sorafenib arm. The majority of patients in the ≥65 years subgroup were enrolled in Europe/USA and Japan (66.3% vs 36.9%), had less advanced disease (BCLC Stage B: 33.3% vs 22.3%; Stage C: 66.7% vs 77.7%; extrahepatic spread: 51.4% vs 61.9%; distant metastases: 49.0% vs 58.5%), more satisfactory performance status (ECOG PS 0: 61.2% vs 54.0%), and fewer viral infections (uninfected: 41.6 % vs 24.0%) vs the overall population, respectively. Patients in the ≥65 years subgroup had a numerically longer mOS (18.2 months [95% CI: 11.6, 24.2] vs 14.2 months [95% CI: 10.5, 19.2]) in the tislelizumab vs sorafenib arm, respectively; mOS in the ≥65 years subgroup was longer than in the overall population (15.9 months [95% CI: 13.2, 19.7] vs 14.1 months [95% CI: 12.6, 17.4]) in the tislelizumab arm only. Patients in the ≥65 years subgroup had a higher confirmed ORR (18.7% vs 4.1%; odds ratio 5.4 [95% CI: 2.0, 14.7]) and shorter mPFS (3.1 months [95% CI: 2.1, 4.2] vs 3.9 months [95% CI: 2.3, 5.4]) in the tislelizumab vs sorafenib arm, respectively. Similar to the overall population, tislelizumab-treated patients in the ≥65 years subgroup experienced lower incidences of ≥grade 3 treatment-emergent adverse events (46.6% vs 62.5%) and ≥grade 3 treatment-related adverse events (20.3% vs 52.5%) vs sorafenib-treated patients.
In the subgroup of patients aged ≥65 years in the RATIONALE-301 trial, tislelizumab demonstrated numerically longer mOS and a higher ORR vs sorafenib; the longer mOS observed with tislelizumab in this subgroup vs the overall population could be attributed to regional imbalances and more favorable baseline characteristics observed in the subgroup. Tislelizumab showed a favorable safety profile vs sorafenib in the ≥65 years subgroup, consistent with the overall population.
NCT03412773.
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.
BeiGene, Ltd.
This study was sponsored by BeiGene, Ltd.
A. Vogel: Honoraria (self): AstraZeneca, Amgen, BeiGene, Böhringer Mannheim, BMS, BTG, Daichi-Sankyo, EISAI, GSK, Imaging Equipment Ltd (AAA), Incyte, Ipsen, Jiangsu Hengrui Medicines MSD, PierreFabre, Roche, Servier, Sirtex, Tahio, Terumo; Advisory / Consultancy: AstraZeneca, Amgen, BeiGene, Böhringer Mannheim, BMS, BTG, Daichi-Sankyo, EISAI, Incyte, Ipsen, MSD, PierreFabre, Roche, Servier, Sirtex, Tahio, Terumo. M. Kudo: Honoraria (self): Eli Lilly, Bayer, Eisai, Chugai, Takeda, AstraZeneca; Advisory / Consultancy: Chugai, Roche, AstraZeneca, Eisai; Research grant / Funding (institution): Taiho, Otsuka, EA Pharma, AbbVie, Eisai, Chugai, GE Healthcare. Y. Chen: Full / Part-time employment: Beigene. F. Boisserie: Shareholder / Stockholder / Stock options: BeiGene; Full / Part-time employment: BeiGene USA, Inc. R. Abdrashitov: Shareholder / Stockholder / Stock options: BeiGene USA Inc; Full / Part-time employment: BeiGene USA Inc. R. Finn: Advisory / Consultancy: AstraZeneca, Eisai, CStone, Merck BMS, Bayer, Exelixis, Roche/ Genentech, Pfizer, Eli Lilly, AstraZeneca (Data Safety or Advisory Board); Speaker Bureau / Expert testimony: Genentech; Research grant / Funding (institution): Bayer, Pfizer, Eisai, Roche, Merck, Genentech, BMS, Eli Lilly. All other authors have declared no conflicts of interest.
