Main Session
Sep 30
SS 36 - GI 3: Liver - Checking in on Inhibitors, inSPECTing Liver Function, and Making Progress Oligo-ly

306 - Toripalimab Combined with Radiotherapy vs. Sorafenib in Advanced Hepatocellular Carcinoma with First Branch (Vp3) or Main Trunk (Vp4) Portal Vein Thrombosis: A Prospective, Open-Label, Randomized Trial

12:45pm - 12:55pm PT
Room 22/23

Presenter(s)

Bo Chen, MD - National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, Beijing

B. Chen1, Y. Zhai1, Y. Zhang2, F. Wu3, L. Wang3, Z. Li2, F. Ye2, S. Wang1, Y. Zong4, Z. Yang4, Z. Li4, J. Lin2, W. Sun2, D. Yan2, Y. Song5, W. Zhang5, Y. Sun5, X. Bi2, and H. Zhao2; 1State Key Laboratory of Molecular Oncology and Department of Radiation Oncology, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, 2National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, 3Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, 4Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, 5Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

Purpose/Objective(s): Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) in the first branches (Vp3), or in the main trunk (Vp4), is associated with a particularly poor prognosis and can be fatal. Effective therapeutic options are limited. This randomized, open-label study investigated first-line toripalimab plus radiotherapy versus sorafenib in patients with HCC with PVTT of Vp3-4.

Materials/Methods: This randomized, open-label Phase 3 study was conducted at one specialist cancer hospital in China. Adults (18–80 years) with HCC and Vp3 or 4 PVTT were randomized (2:1) to either toripalimab (240 mg by IV every 3 weeks) combined with radiotherapy (40-60 Gy in 10 fractions), or sorafenib 400 mg orally twice daily. The primary endpoint was time to progression (time from enrolment to disease progression), per RECIST v1.1, evaluated in all patients assigned to treatment. The trial was terminated when the protocol-defined stopping rule was met at the first interim analysis, reported here.

Results: From March 10, 2021 to March 27, 2024, 68 patients were screened and 36 (males: n=33; females: n=3) randomized to toripalimab plus radiotherapy (n=25) or sorafenib (n=11). At this interim analysis, (data cut-off: December 27, 2024), the median TTP was significantly longer in the toripalimab plus radiotherapy group (median follow-up: 17.9 months) versus sorafenib (median follow-up: 10.9 months): 5.6 versus 0.9 months, HR 0.155 (95% CI (0.068-0.352); P<0.001. Prolong median overall survival time was observed in for toripalimab plus radiotherapy versus sorafenib (not reached versus 10.9 months; HR 0.120 (95% CI 0.032–0.447); P<0.001). The independent review committee (IRC)-assessed best response assessed by RECIST v1.1, showed a significantly higher ORR (44.0% vs. 9.1%, P=0.041) and disease control rate (DCR) (72.0% vs. 27.3%, P=0.012) for patients in the toripalimab plus radiotherapy group versus the sorafenib group. A similar result was observed using mRECIST, but the difference in ORR between the two groups did not reach significance (52% vs. 18.2%; P=0.058). The DCR for PVTT was significantly higher in the toripalimab plus radiotherapy group compared to the sorafenib group by RECIST v1.1 and mRECIST (100% vs. 54.5% P<0.001, 100% vs. 63.6%, P=0.001).AEs were experienced by 88% (n=22) and 64% (n=7), and Grade =3 AEs by 24.0% (n=6) and 36.4% (n=4), of patients in the toripalimab plus radiotherapy and sorafenib groups, respectively. There were no treatment-related deaths.After the discussion of the independent data monitoring committee meeting, the trial was terminated.

Conclusion: Toripalimab plus radiotherapy resulted in a clinically meaningful improvement in time to progression compared with sorafenib in patients with HCC and Vp3/4 PVTT and represents a promising treatment for this patient population, who have a very poor prognosis and limited evidence-based treatment options. The study was registered at ClinicalTrials.gov (NCT04709380).