Exelixis, Inc. (NASDAQ:EXEL) today reported positive preliminary data from the cohort of hepatocellular carcinoma (HCC) patients participating in the ongoing phase 2 randomized discontinuation trial (RDT) of cabozantinib. Allan Lee Cohn, M.D., Medical Director of Research at the Rocky Mountain Cancer Centers, will present the data today at 11:45 a.m. PST as part of the 2012 Gastrointestinal Cancers Symposium (Abstract #261). The meeting is taking place in San Francisco, California.
The week 12 disease control rate (PR and SD at week 12) was 68%. Evidence of objective tumor regression was observed in 78% of patients, including those with or without prior sorafenib therapy. The best radiologic response per RECIST in the lead-in stage of the study for 36 patients with at least one post-baseline measurement was confirmed partial response (cPR) in 2 patients and stable disease (SD) in 32 patients. One additional patient had a partial response that was confirmed after the patient completed the lead-in stage and proceeded to the randomized component of the trial. Median progression-free survival (PFS) was 4.2 months, and was similar for sorafenib-pretreated and sorafenib-naïve patients.
The results include data from 41 patients with advanced hepatocellular carcinoma (HCC) with measurable disease at baseline and documented progressive disease per RECIST criteria. Eligible patients had Child-Pugh Score A. Seventy-one percent of patients had one prior line of systemic therapy: 24% had received prior chemotherapy and 56% prior tyrosine kinase inhibitor (TKI) therapy, including 51% previously treated with sorafenib. Extrahepatic spread of disease was present in 70% of subjects, median AFP level was 368 and thrombocytopenia was present in 34%. Patients in the open label 12 week lead-in stage of the trial received a starting dose of 100 mg of oral cabozantinib daily.
A >50% reduction in the tumor marker alpha-fetoprotein (AFP) serum level was observed in 10 (38%) of 26 patients with AFP levels of ≥ 20 ng/mL at baseline and at least one post baseline measurement.
"We are very encouraged by the disease control rates observed in this population of patients with hepatocellular carcinoma," said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. "Importantly, the similar PFS data in patients with and without prior sorafenib therapy is noteworthy, given the widespread use of this treatment as first-line therapy for HCC. These data warrant further study and we hope to investigate cabozantinib further in HCC as part of our recently announced Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute's Cancer Therapy and Evaluation Program."
The tolerability of cabozantinib in patients with HCC was similar to that of other TKIs. The most frequently reported ≥ grade 3 adverse events (AEs), regardless of causality in the 41 patients in the HCC cohort were: diarrhea (17%), palmar-plantar erythrodyesthesia (15%), thrombocytopenia (10%), asthenia (7%), aspartate aminotransferase elevation (5%), and fatigue, nausea, vomiting, hypertension, and weight decrease (2% each).There were no grade 5 events related to cabozantinib.
"These compelling results highlight cabozantinib's potential clinical utility in HCC," said Dr. Cohn. "In particular, the anti-tumor activity in patients with and without prior sorafenib therapy suggests that we may see additional benefit for pretreated and treatment-naïve patients through simultaneous inhibition of MET and VEGF signaling, rather than VEGF alone. Further study of cabozantinib in patients with HCC is clearly warranted."
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