CALGB 80802 (Alliance): Impact of Sorafenib with and without Doxorubicin on Hepatitis C Infection in Patients with Advanced Hepatocellular Carcinoma.

Autor:	Abou-Alfa GK; Memorial Sloan Kettering Cancer Center, New York, New York.; Weill Medical College of Cornell University, New York, New York., Geyer SM; Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, Minnesota., Nixon AB; Duke Cancer Institute, Duke University Health System, Durham, North Carolina., Innocenti F; University of North Carolina, Chapel Hill, North Carolina., Shi Q; Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, Minnesota., Kumthekar P; Alliance for Clinical Trials in Oncology Protocol Office, Chicago, Illinois., Jacobson S; Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, Minnesota., El Dika I; Memorial Sloan Kettering Cancer Center, New York, New York.; Weill Medical College of Cornell University, New York, New York., Yaqubie A; Memorial Sloan Kettering Cancer Center, New York, New York., Lopez J; Memorial Sloan Kettering Cancer Center, New York, New York., Huang B; Memorial Sloan Kettering Cancer Center, New York, New York., Tang YW; Memorial Sloan Kettering Cancer Center, New York, New York., Wen Y; University of Chicago, Chicago, Illinois., Schwartz LH; Columbia University Medical Center, New York, New York.; New York-Presbyterian Hospital, New York, New York., El-Khoueiry AB; USC Norris Comprehensive Cancer Center, Los Angeles, California., Knox JJ; Princess Margaret Cancer Centre, Toronto, Ontario, Canada., Rajdev L; Lenox Hill Hospital, New York, New York., Bertagnolli MM; Brigham and Women's Hospital, Boston, Massachusetts., Meyerhardt JA; Dana-Farber/Partners Cancer Care, Boston, Massachusetts., O'Reilly EM; Memorial Sloan Kettering Cancer Center, New York, New York.; Weill Medical College of Cornell University, New York, New York., Venook AP; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California.
Jazyk:	angličtina
Zdroj:	Cancer research communications [Cancer Res Commun] 2024 Mar 07; Vol. 4 (3), pp. 682-690.
DOI:	10.1158/2767-9764.CRC-22-0516
Abstrakt:	Sorafenib blocks nonstructural protein 5A (NS5A)-recruited c-Raf-mediated hepatitis C virus (HCV) replication and gene expression. Release of Raf-1-Ask-1 dimer and inhibition of Raf-1 via sorafenib putatively differ in the presence or absence of doxorubicin. Cancer and Leukemia Group B (CALGB) 80802 (Alliance) randomized phase III trial of doxorubicin plus sorafenib versus sorafenib in patients with advanced hepatocellular carcinoma (HCC), showed no improvement in median overall survival (OS). Whether HCV viral load impacts therapy and whether any correlation between HCV titers and outcome based on HCV was studied. In patients with HCV, HCV titer levels were evaluated at baseline and at multiple postbaseline timepoints until disease progression or treatment discontinuation. HCV titer levels were evaluated in relation to OS and progression-free survival (PFS). Among 53 patients with baseline HCV data, 12 patients had undetectable HCV (HCV-UN). Postbaseline HCV titer levels did not significantly differ between treatment arms. One patient in each arm went from detectable to HCV-UN with greater than 2 log-fold titer levels reduction. Aside from these 2 HCV-UN patients, HCV titers remained stable on treatment. Patients who had HCV-UN at baseline were 3.5 times more likely to progress and/or die from HCC compared with HCV detectable (HR = 3.51; 95% confidence interval: 1.58-7.78; P = 0.002). HCV titer levels remained unchanged, negating any sorafenib impact onto HCV titer levels. Although an overall negative phase III study, patients treated with doxorubicin plus sorafenib and sorafenib only, on CALGB 80802 had worse PFS if HCV-UN. Higher levels of HCV titers at baseline were associated with significantly improved PFS. Significance: Sorafenib therapy for HCC may impact HCV replication and viral gene expression. In HCV-positive patients accrued to CLAGB 80802 phase III study evaluating the addition of doxorubicin to sorafenib, HCV titer levels were evaluated at baseline and different timepoints. Sorafenib did not impact HCV titer levels. Despite an improved PFS in patients with detectable higher level HCV titers at baseline, no difference in OS was noted. (© 2024 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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