Adding aflibercept to docetaxel and prednisone did not boost survival times and nearly doubled the rate of grade 3-4 adverse events, compared with docetaxel and prednisone alone in men with metastatic castration-resistant prostate cancer.
The results of the phase III VENICE trial are yet another negative outcome for a regimen that adds a targeted agent to the standard first-line chemotherapy for metastatic castration-resistant prostate cancer (mCRPC), said lead author Dr. Ian Tannock, professor at the University of Toronto and a medical oncologist at UHN Princess Margaret Cancer Center, Toronto.
Aflibercept is a potent anti-angiogenic agent that binds to VEGF-A, VEGF-B, and placental growth factor (PfGF), he said at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.
Although 866 articles in PubMed have linked VEGF to prostate cancer, targeting VEGF in clinical trials has failed so far, commented Dr. William Oh, who was not involved in the study. Dr. Oh is chief of hematology and medical oncology at Tisch Cancer Institute and Icahn School of Medicine at Mount Sinai, New York.
In the VENICE (Aflibercept in Combination With Docetaxel in Metastatic Androgen Independent Prostate Cancer) study, researchers randomized 1,224 patients with mCRPC treated with docetaxel (75 mg/m2 IV every 3 weeks) and oral prednisone (5 mg, given twice a day) to receive placebo or aflibercept (6 mg/kg every 3 weeks). The aflibercept had a median of seven cycles of therapy and the placebo group had a median of eight cycles.
The patients’ median age was 68 years, and their baseline characteristics were similar in each arm of the study. Most of the patients had a European Cooperative Oncology Group (ECOG) performance status of 0 or 1 and had received three or more hormonal therapies.
The primary end point was overall survival. Secondary end points included PSA response, time to occurrence of skeletal-related events, and progression free survival. By the median follow-up time of 3 years, 873 patients had died.
Overall survival was nearly identical between the two arms: 22.1 months in aflibercept arm vs. 21.2 months in placebo (hazard ratio = 0.94; P = .38).
The secondary end points were either nearly equal between the two arms or favored the placebo arm: PSA response was 68.6% in aflibercept arm vs. 63.5% for placebo (P = 0.075); time to skeletal-related event was 15.3 months for aflibercept vs. 15.0 for placebo (HR = 0.94, P = .31); and progression-free survival was 6.9 months (aflibercept) vs. 6.2 (placebo).
Grade 3-4 adverse events occurred in 77% of the aflibercept group and 48% of the placebo group; adverse events led to discontinuation of therapy for 44% of the aflibercept group and 21% of the placebo group. Fatal adverse events occurred in 5.6% of patients in the aflibercept arm and in 3.3% in the placebo arm.
Adverse events included hypertension, stomatitis, appetite disorders, diarrhea, dehydration, epistaxis, dysphonia, cough, headache, and infections.
Dr. Tannock has received research funding from Sanofi, which funded the study along with Regeneron Pharmaceuticals. Dr. Oh has been a consultant or advisor for Amgen, Astellas Pharma, Bayer, Bellicum Pharmaceuticals, Dendreon, Janssen Biotech, Medivation, and Pfizer. He has received research funding from Millennium.
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