Data from two trials presented at the European Society for Medical Oncology (ESMO) 2012 Congress show that two new agents, ODM-201 and tasquinimod, are active in prostate cancer.
One trial was a first-in-man escalating-dose phase I/II trial with the agent ODM-201, a new-generation androgen receptor antagonist, in patients with progressive metastatic castration-resistant prostate cancer (mCRPC). At 12 weeks of treatment, the agent showed significant reductions (of greater than 50%) in prostate-specific antigen (PSA) levels in 87% (13 of 15) of patients—including all 6 patients who had previously been treated with docetaxel(Drug information on docetaxel). All patients in the trial had a partial response or stable disease at 12 weeks. The oral drug, taken twice daily, was well tolerated. Based on these results, the phase II portion of the study in mCRPC started in June. The trial plans to enroll over 100 patients.
“Preliminary antitumor activity of nearly 90% of patients with more than 50% decline in PSA is clearly impressive and very promising,” Christophe Massard, MD, of the Institut Gustave-Roussy in Villejuif, France, and presenter of the data, told Cancer Network.
Based on preclinical animal models, ODM-201, unlike other anti-androgens, does not enter the brain. Massard noted that the drug may be promising for both metastatic and non-metastatic prostate cancer patients—pending results of further clinical trials. A large phase I/II trial that aims to recruit 130 patients is ongoing in the United States and Europe to confirm these preliminary results.
“Prostate cancer is clearly a heterogeneous disease,” said Massard. “The challenge of the future will be to understand the molecular mechanism of sensitivity or resistance to androgen receptor targeting therapies or other drugs.”
Biomarkers Correlate With Response Rate in Tasquinimod Study
An analysis of angiogenesis and immune biomarkers from participants of a randomized, phase II trial with tasquinimod has shown the agent active in chemotherapy-naive asymptomatic patients with mCRPC. The results were presented at the ESMO 2012 Congress by Michael Carducci, MD, of the Johns Hopkins Medical Institute in Baltimore. “The biomarker data is consistent with our hypothesis, but remains preliminary and exploratory,” Carducci told Cancer Network.
Tasquinimod has both an immunomodulatory and anti-angiogenic activity, but the exact mechanism of action is unknown.
Biomarkers such as PSA, lactate dehydrogenase (LDH), bone alkaline phosphatase (BAP), VEGF-A, VEGF-C, and others were analyzed in serum or plasma from patients both before and during therapy. The biomarker analysis, according to the study authors, supports an effect of tasquinimod on angiogenesis and immunomodulation. Changes in levels of three markers—transforming growth factor-beta (TGF-ß), thrombospondin-1 (TSP-1), or VEGF-C are potential markers for patient treatment benefit. PSA levels did not correlate to the fluctuations of the other biomarkers.
Overall survival data from the 206-patient phase II trial presented in June at the annual meeting of the American Society of Clinical Oncology (ASCO) showed a median overall survival of 33.4 months in the experimental arm compared to 30.4 months in the placebo arm (P = .49). A stronger trend toward a survival benefit was seen in those patients who had bone metastases—median overall survival of 34.2 months in the tasquinimod arm and 27.1 months in the placebo arm (P = .19). The 6-month progression-free proportions were 69% for the tasquinimod arm compared to 37% in the placebo arm (P < .0001). The median progression-free survival was 7.6 compared to 3.3 months for the tasquinimod and placebo groups, respectively (P = .0042).
A controlled phase III study is ongoing in asymptomatic or mildly symptomatic patients with mCRPC. The trial aims to accrue 1,200 patients, randomized 2:1, to either tasquinimod or placebo. Currently, approximately 1,000 patients have been accrued. Carducci said that if the results are positive and the drug “continues with the safety profile that we have seen over the phase II and current phase III study, men seeking to avoid chemotherapy will move to this agent, most likely after use of other approved agents such as sipuleucel-T, abiraterone, or enzalutamide.” According to Carducci, the exploratory biomarker data will be used to generate new hypotheses to be evaluated in the current ongoing phase III study to guide which patients will likely benefit best from tasquinimod.