Laurie Bouck

November 05, 2008

November 5, 2008 (San Francisco, California) — Certain tumor and plasma biomarkers can indicate whether sorafenib (Nexavar, Bayer HealthCare Pharmaceuticals in collaboration with Onyx Pharmaceuticals) will extend the time to progression of hepatocellular carcinoma (HCC), according to new research.

In an analysis of data from 602 advanced HCC patients from the phase 3 Study of Heart and Renal Protection (SHARP), researcher Joseph Llovet, MD, from the Barcelona Clinic Liver Cancer Group, Hospital Clinic Barcelona, in Spain, and the Division of Liver Diseases Recanati/Miller Transplantation Institute, Mount Sinai School of Medicine, in New York City, and colleagues looked at 7 biomarkers to see how sorafenib affected disease progression and survival. Dr. Llovet presented his findings here at The Liver Meeting 2008, the 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).

Sorafenib is an approved treatment for liver cancer and renal cancer. It is also being investigated as an adjuvant therapy for liver cancer, renal cancer, breast cancer, melanoma, and non-small-cell lung cancer

In Dr. Llovet's study, patients were randomized to receive either oral sorafenib 400 mg twice a day or placebo. Researchers used tumor biopsies to analyze the biomarker pERK, and analyzed 6 plasma biomarkers (BEGF, soluble (s) vascular endothelial growth-factor receptor [VEGFR]-2, s VEGFR-3, s-c-Kit, hepatocyte growth factor [HGF], and Ras p21) at baseline and 12 weeks. About half the patients were available at 12 weeks for plasma analysis.

Independently, VEGF and c-Kit were associated with survival. At 12 weeks, patients in the sorafenib cohort had decreased levels of most of the plasma biomarkers, including c-Kit (–33.9%; P < .0001), but increased VEGF levels (+195.7%; P = .010).

"VEGF plasma levels were independently associated with survival in HCC patients," Dr. Llovet and colleagues write in the study abstract, although "low HGF levels and high c-Kit levels were associated with longer survival in patients treated with sorafenib."

Fewer data were available for the tumor biomarker (n = 107), but patients with high pERK (based on area percent staining positive) had a longer time to progression than those with low pERK. Combined with lowered HGF levels, positive pERK increased time to progression in the sorafenib cohort.

Session moderator and AASLD president Arthur J. McCullough, MD, found the data "very impressive." He told Medscape Gastroenterology that "it's very early, but it's a concept more important than the individual data, that you will be able now to predict early on in treatment who will respond to therapy." Although it is too early to apply the data to clinical practice, he said, sorafenib combined with other treatments could add an unknown amount of time to a patient's life.

In other sessions on sorafenib, audience members questioned whether the price of sorafenib, which runs more than $5000 per month, is worth the 2 or 3 months of extended life for patients with terminal liver cancer.

Dr. Llovet has received research support from Bayer. Four of Dr. Llovet's coauthors are employed at Bayer; the fifth consults for Bayer. Dr. McCullough has received research support from Takeda.

The Liver Meeting 2008: 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD): Abstract 149. Presented November 3, 2008.

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