Several key prostate cancer presentations were given June 3rd, during morning sessions of the 2012 American Society of Clinical Oncology (ASCO) Annual Meeting. Two general poster presentations that generated lively discussions and a definite buzz among attendees were those focused on oncotherapies from Dendreon Corporation and Tokai Pharmaceuticals.
Both presentations highlighted results from clinical trials of drugs used to treat castration resistant prostate cancer (CRPC). This type of prostate cancer has proven particularly difficult to treat; creating an urgent need for the development of oncotherapies that will improve overall survival rates in men with CRPC.
Dendreon, a biotechnology company whose initial product PROVENGE® (sipuleucel-T) received FDA approval in 2010, participated in the General Poster Session for Genitourinary Cancer. The presentation, entitled “Overall Survival (OS) Benefit with Sipuleucel-T by Baseline PSA; An Exploratory Analysis from the Phase 3 IMPACT Trial”, showed details of the study, identifying when treatment with PROVENGE® delivers the greatest benefit to patients with CRPC.
PROVENGE® – Best Used Between the Mountains
Dr. Nicholas Vogelzang, Chair of ASCO’s Cancer Communications Committee and investigator for both Tokai and Dendreon comments, “Just like any other subset analysis, the findings are suggestive at best; I asked a number of questions and was somewhat critical of the data.” The study showed that the lower the patient’s baseline PSA, the greater the benefit. In other words, the least symptomatic patients benefitted the most from treatment with PROVENGE®.
“This indicates a biologically plausible effect in lower symptomatic patients,” says Vogelzang. The more symptomatic a patient is, the less effective treatment with PROVENGE®. “A graded effect of any sort shows that there is indeed a real effect.” He went on to explain that this indicates that early use of PROVENGE® will yield the best results, using the drug in between what Vogelzang refers to as the three mountains of prostate cancer: hormone therapy, local therapy (surgery), and chemotherapy. He suggests using the drug after hormone therapy ceases to keep the disease in check, but before chemotherapy.
Dendreon Corporation and its lead drug, PROVENGE®, have a history of stiring up considerable controversy and debate over the efficacy of the drug and its future in the arsenal of prostate cancer oncotherapies.
Tokai Pharmaceuticals’ Evaluates Lead Candidate – Galeterone
Tokai Pharmaceuticals’ general poster presentation highlighted results from their Phase 1 trial of developmental drug, galeterone (TOK-001). The presentation, entitled “Phase I clinical trial of galeterone (TOK-001), a multifunctional anti-androgen and CYP17 inhibitor in castration resistant prostate cancer (CRPC)” evaluated safety and proof-of-concept of the company’s lead developmental oncotherapy. The drug interrupts the growth and survival of prostate cancer cells by targeting the primary driver of CRPC: androgen receptor signaling.
President and CEO of Tokai Pharmaceuticals, Martin D. Williams, commented on the company’s claim that the drug is the first of its kind. He explained that galeterone is different than other experimental CRPC therapies because it combines three distinct mechanisms of action, employing a multi-target approach in one oral drug.
In fact, galeterone does represent the only developmental cancer treatment to use such an approach. Other experimental CRPC oncotherapies target androgen receptor signaling through a single mechanism of action. According to Williams, galeterone blocks ligand synthesis, blocks ligand receptor binding, and degrades the receptor itself using a triple mechanism action, via its single oral compound.
Why does Galeterone’s multi-target action hold more promise for effective treatment of CRPC than single action experimental therapies? “Cancer cells develop a resistance to drug therapies through mutation and change. Galeterone’s triple mechanism action may prevent prostate cancer cells from developing resistance,” says Vogelzang. If the drug can prevent cancer cells from developing a resistance to therapy, galeterone holds the potential to significantly increase overall survival rates and life expectancy for men with CRPC.
The phase I clinical trial of galeterone (TOK-001) suggests the drug has great potential for effectively treating CRPC. Even so, Vogelzang had this to say, “The pharmacokinetics are not optimal, causing too much variability with who benefitted from treatment with the drug. It will be reformulated with improved pharmacokinetics before the Phase 2 clinical trial begins later this year.”
Cabozantinib Interim Data Positive in mCRPC
Additional buzz in the treatment of prostate cancer came earlier today (Tuesday June 5th) when Dr. Matthew R. Smith, Director of the Genitourinary Malignancies Program at the Massachusetts General Hospital Cancer Center presented cabozantinib interim data. Oral abstract #4513, “Cabozantinib (XL 184) in chemotherapy-pretreated metastatic castration resistant prostate cancer (mCRPC): Results from a phase II nonrandomized expansion cohort (NRE)”, highlighted the positive effects cabozantinib has on metastatic bone lesions and soft tissue disease. It also demonstrate a positive impact on bone related pain and narcotic use, as well as biomarkers of both bone formation and bone resorption.
Improvement in patient bone scans and bone pain management elicited considerable discussion among ASCO attendees, with progression free survival (PFS) also generating a positive buzz. Cabozantinib is poised to become an oncotherapeutic agent of the future; phase 3 data will be eagerly anticipated.
The PSA Controversy: An Inside Scoop on ASCO’s Stance
When asked what he thought about the US Public Health Service’s recently released statements that routine PSA testing does more harm than good. “ASCO has developed a soon-to-be-released policy regarding the controversy over routine PSA testing,” revealed Vogelzang.
He summarized the policy by stating that ASCO shares the US Public Health Services concerns about the risk of over-diagnosis and associated side effects; PSA testing still has a critical role to play in early diagnosis and overall survival of younger men; routine PSA testing in younger men increases life expectancy by 10 years or more; research into more accurate testing is urgently needed; PSA testing is almost, but not quite as good as mammography for early detection. Vogelzang comments, “In fact, mortality from prostate cancer has been dropping steadily for the past five years, most likely due to routine PSA testing.”
According to the American Cancer Society, physicians diagnose over 241,000 new cases of prostate cancer annually. Over 28,000 men die each year from prostate cancer. Additional research is urgently needed in the development of effective oncotherapies for treating prostate cancer, in general, and CRPC specifically.
