An Independent Review of Camrelizumab-Rivoceranib Combination Therapy for the Treatment of Hepatocellular Carcinoma and Rivoceranib for Gastric Cancer

Posted by Michael A. S. Guth on September 8th, 2024

https://biomedres.us/pdfs/BJSTR.MS.ID.009118.pdf 

https://www.researchgate.net/publication/383861594_An_Independent_Review_of_Camrelizumab-Rivoceranib_Combination_Therapy_for_the_Treatment_of_Hepatocellular_Carcinoma_and_Rivoceranib_for_Gastric_Cancer/

Abstract: The CARES-310 clinical trial compared the safety and efficacy of camrelizumab, an anti-PD-1 antibody, combined with rivoceranib, a vascular endothelial growth factor receptor 2 (VEGFR2)-targeted tyrosine kinase inhibitor (TKI), versus the obsolete standard of care sorafenib as first-line (1L) treatment for unresectable hepatocellular carcinoma (uHCC). In this independent analysis of the CARES-310 trial, potential bias in the choice of comparator and the clinical significance of the results are reexamined. Although rivoceranib (also known as “apatinib”) is approved in China to treat patients with advanced gastric cancer, the clinical trial conducted in the USA for patients with gastric cancer seems to indicate missed endpoints and weak evidence to justify FDA approval. Due to a nondisclosure agreement, the principal investigators are unable to comment on these results. However, from a table of functional benefits and harms, readers might well conclude that palliative hospice care is non-inferior to rivoceranib for patients with Stage 4 gastric cancer.

RCCEP can cause red-nevus-like, pearl-like, mulberry-like, patch-like, and even tumor-like skin lesions in patients with HCC

https://biomedres.us/pdfs/BJSTR.MS.ID.009118.pdf

Conclusion

The CARES-310 clinical trials produced a new longest median OS of 23.8 months for patients with uHCC treated with C-R.  However, the CARES-310 clinical trial may have been overweighted with an Asian population with preexposure to antiviral therapy and better preservation of liver function at time of HCC diagnosis. Conversely, the CARES-310 trial was underweighted with Western patients who have NAFLD, diabetes, obesity, and other co-morbidities and confounding factors.  Oncologists already have 1L patient treatment experience for uHCC with Roche’s FDA-approved anti-PD-L1/VEGF combination Tecentriq and Avastin and with AstraZeneca’s CTLA-4 checkpoint inhibitor Imjudo combined with its PD-L1 antagonist Imfinzi for treatment of uHCC. It would be useful to compare the C-R proposed therapy with these drug combinations and determine if C-R maintains an 8.6-month median OS advantage over the new comparator(s).

When rivoceranib plus hospice care was compared to hospice care alone in a clinical trial of patients with advanced gastric cancer or gastroesophageal adenocarcinoma, the results data were mixed. For some measures of functional benefits and harms, the patients with hospice care alone had higher percentages for certain functional benefits and lower percentages for some harms and adverse events.  The rivoceranib-treated group failed to consistently outperform hospice care alone using these measures.  Based on those benefits and harms, hospice care alone was not inferior to rivoceranib + hospice care, which calls into question the underlying clinical value, if any, of rivoceranib to the American patient population with advanced gastric cancer.  The fact that rivoceranib, known as apatinib, is approved in China for treatment of advanced gastric raises anew questions about fundamental differences in patient populations between China and the USA or Europe for medical conditions such as uHCC and advanced gastric cancer.

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Acknowledgments

Christopher Coleman, Pharm.D., provided useful comments.

Conflict of Interests

None.

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