The combination use of the PD-1 inhibitor camrelizumab and the VEGFR-2 TKI rivoceranib significantly delayed cancer recurrence and improved overall survival compared with Nexavar (sorafenib) treatment in patients with unresectable hepatocellular carcinoma (HCC), according to study results released at the 2023 ESMO Congress.5,6
About Liver Cancer
Each year in the United States, there are more than 25,000 individuals diagnosed with primary liver cancer and more than 18,000 deaths from the disease. Liver cancer is the fifth leading cause of cancer death among U.S. men, and the ninth leading cause of cancer death among U.S. women. Worldwide, more than 1 million individuals are diagnosed with liver cancer each year. Hepatocellular carcinoma accounts for 80-90% of all primary liver cancers.1-4
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults. It begins in the liver cells known as hepatocytes.
- Cholangiocarcinoma is cancer that develops in the cells that line the bile ducts within the liver.
- Hepatoblastoma is a rare type of liver cancer that develops in children.
- Angiosarcoma and Hemangiosarcoma are rare cancers that start in the blood vessels of the liver.
Treatment of early-stage liver cancer often consists of local liver directed therapies and/or liver transplant. The cornerstone treatment of more advanced disease however is systemic chemo-immunotherapy designed to eradicate cancer cells throughout the body. Historically advanced HCC was treated with single agent drugs like Nexavar, but these have more recently been replaced with immunotherapy drug combinations.
About Camrelizumab
Camrelizumab is a type of immune therapy called a “checkpoint inhibitor” – a monoclonal antibody directed against the cell surface programmed death-1 (PD-1, PCD-1) receptor. Camrelizumab binds to and blocks the binding of PD-1 expressed on immune cells and prevents their activation and downstream signaling pathways which restores immune function of cytotoxic T lymphocytes (CTLs) and the cell-mediated immune responses against cancer cells.
About Rivoceranib
Rivoceranib is an inhibitor of the vascular endothelial growth factor receptor 2 (VEGFR-2), a primary pathway that facilitates the process of blood vessel development which is necessary to bring nutrients to growing cancer cells called “tumor angiogenesis” VEGFR-2 inhibition is a clinically validated approach to limit cancer cell growth with documented effectiveness in several types of cancer impacting the gastrointestinal system.
In the current clinical trial patients with advanced HCC were treated with the combination of camrelizumab intravenously plus oral daily rivoceranib or oral nexavar and their outcomes directly compared.
The confirmed objective response rate 25.4% with camrelizumab plus rivoceranib compared with 5.9% for nexaver and the median duration of response was 14.8 months with camrelizumab plus rivoceranib and 9.2 months for nexavar. At 18 months from treatment initiation 61% of patients treated with the combination were alive compared to 45% of those treated with nexavar monotherapy.
The most frequently reported significant side effects with camrelizumab plus rivoceranib combination were hypertension, palmar-plantar erythrodysesthesia low blood platelet counts and mildly elevated abnormal liver enzymes.
During a discussion of the findings, R. Katie Kelley, MD, from the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco, described potential advantages with the use of an oral angiogenesis inhibitor, but also cautioned that careful patient selection was required, given the hepatotoxicity seen with the combination. Moreover, she noted challenges with extrapolating the data to a non-Asian population, particularly given the high rates of hepatitis B virus infection seen in the underlying etiology.
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References
- National Cancer Institute. Adult Primary Liver Cancer Treatment (PDQ®). Available here
- Ibrahim S, Chen CL, Wang SH et al. Liver resection for benign liver tumors: indications and outcome. American Journal of Surgery. 2007;193:5-9.
- American Cancer Society. Cancer Facts & Figures 2022. Available here
- National Cancer Institute. What You Need to Know About™ Liver Cancer. Available at: www.cancer.gov/cancertopics/wyntk/liver
- Qin S, Chan SL, Gu S, et al. Camrelizumab (C) plus rivoceranib (R) vs. sorafenib (S) as first-line therapy for unresectable hepatocellular carcinoma (uHCC): a randomized, phase III trial. Ann Oncol. 2022;33(suppl 7). doi:10.1016/j.annomnc.2022.08.032.
- Kang H, Ahn M-J, Muzaffar J, et al. A phase 2 study of the oral vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor, rivoceranib, for recurrent or metastatic (R/M) adenoid cystic carcinoma (ACC). J Clin Oncol. 2022;40 (suppl 16):abstr 6020. doi:10.1200/JCO.2022.40.16_suppl.6020.
