ORLANDO, FL— The news was promising regarding several drugs for the treatment of prostate cancer at the recent ASCO Genitourinary Cancers Symposium held February 17-19, 2011 An extension-phase study of degeralix, approved by the FDA in 2008, confirmed the efficacy of this drug versus leuprolide. Other positive studies focused on drugs in various stages of development, including abiraterone, cabozantinib, and MDV3100.
Degarelix (Firmagon, Ferring)
An open-label extension study of a phase III pivotal study found that degarelix slowed prostate-specific antigen (PSA) progression significantly in patients with prostate cancer treated with leuprolide for 12 months and then switched to degarelix (Abstract 12). This benefit was consistent with the primary results of the phase 3 trial showing that degarelix was superior to leuoprolide in the rate of androgen suppression, PSA suppression, risk of PSA failure or death, and reduced levels of a biomarker associated with metastatic death. Data from the open-label extension study also showed that degarelix was associated with a significant increase in the interval before 25% of patients experienced PSA failure or death. Mean follow-up was 27.5 months.
Lead author Neil Shore MD, of the Carolina Research Center in Myrtle Beach, South Carolina, said that the data support the use of degarelix as first-line androgen deprivation therapy based on the durability of the significant progression-free survival benefit that emerged when degarelix was compared with leuprolide in the randomized phase 3 trial and was sustained in the open-label phase.
The data presented by Dr Shore focused on the group of patients treated with degarelix 80 mg, which is the approved dose. Progression of PSA was slowed in all men in the extension phase as well as a subgroup of men with PSA values >20 ng/mL (P = .003)
Abiraterone (Cougar Technology, a subsidiary of Johnson & Johnson)
Interim results of a randomized, controlled phase III trial showed that abiraterone acetate (AA) significantly prolonged overall survival (OS) in patients with metastatic castration resistant prostate cancer (CRPC) who progressed on docetaxel-based chemotherapy, and the survival benefit was consistent across all pre-specified subgroups (Abstract 4). Abiraterone should be considered as a new standard of care, said lead author Howard Scher, MD, chief of the genitourinary oncology service for urology and prostate cancers at Memorial Sloan-Kettering Cancer Center in New York City.
The study enrolled 1200 patients with metastatic CRPC who failed on 1 or 2 previous lines of chemotherapy (at least one with docetaxel). Patients were randomized to AA 1000 mg plus prednisone 5 mg twice daily versus placebo plus prednisone. The two arms were well balanced for demographic and disease characteristics.
AA achieved significantly superior OS versus placebo: a median of 14.8 months versus 10.9 months, representing a 35% relative risk reduction of mortality (P <.0001). The survival benefit was consistent across subgroups in a pre-planned analysis stratified for number of lines of prior chemotherapy, performance status, pain scores, and radiographic progression-free survival (PFS). Total and confirmed PSA response rates were also superior in the abiraterone-treated arm.
Adverse events of all grades and of grades 3 and 4 were similar between the two treatment arms and were manageable.
Session moderator, Oliver Sartor, MD, said, “This is a game-changer. To me this will change practice.” Dr Sartor is director of the prostate cancer program at Tulane University School of Medicine in New Orleans, LA.
Cabozantinib (XL 184, Exelixis)
Cabozantinib (XL 184) achieved dramatic resolution of bone metastases and associated pain, according to updated data from a phase II study. The data were from an open-label, 12-week treatment phase leading into a randomized trial (Abstract 127). The study was based on the first 100 patients enrolled in the trial; 26 dropped out before completing 12 weeks of therapy. At enrollment, about 50% had progressed on docetaxel, 78% had bone metastasis, 50% had significant pain, and 37% required narcotics for pain.
Resolution of bone metastasis was observed in 85% of 62 patients with available bone scans; 8 additional patients had stable disease after 12 weeks of cabozantinib. Of 43 evaluable patients with bone metastases and bone pain, 60% reported improvement in pain at 6 and 12 weeks of treatment with cabozantinib. Of 33 evaluable patients who required narcotics for bone pain, 21 (64%) reported improvement in pain at 6 or 12 weeks, and 13 (46%) decreased or discontinued usage of narcotics. Median progression-free survival had not yet been reached for patients treated with cabozantinib at the time of ASCO GU.
According to preliminary data, the drug appears to have an anti-tumor effect as well. Side effects included fatigue (71% all grades), diarrhea (46%), hand-foot syndrome (19%), decreased appetite (62%), and hypertension (26%).
Additional phase II and III studies are planned. Several experts who were not involved in this study were enthusiastic about what appears to be “remarkable” and “unprecedented” resolution in bone metastasis.
MDV -3100 (Medivation/Astellas Pharma Inc.)
MDV3100 achieved durable antitumor activity as reflected by median times to PSA progression and radiographic progression in men with advanced prostate cancer (Abstract 134, Higano et al). These updated results at 42 months of follow-up of a phase I-II study confirmed interim results of the trial showing antitumor activity with this agent in patients who developed resistance to bicalutamide or other standard anti-androgen treatments.
The phase I-II trial enrolled 140 men with progressive disease between July 2007 and December 2008. Of those, 18 remained on active treatment at the time of ASCO GU. Median time to PSA progression according to protocol-specified criteria had not yet been reached in 65 chemotherapy-naïve patients and was 316 days in 75 patients post-chemotherapy. Median time to radiographic progression was 392 days and 175 days, respectively. Circulating tumor cell counts were available for 128 patients; of these, 70 of 77 (91%) with favorable pre-treatment counts remained favorable post-treatment, and 15 of 51 patients (49%) converted from unfavorable to favorable post-treatment counts.
The drug is currently under evaluation in two randomized, placebo-controlled phase III trials: AFFIRM and PREVAIL. MDV3100 is the first triple-acting, oral androgen receptor antagonist being developed for the treatment of advanced prostate cancer and provides more complete suppression of the androgen receptor pathway than bicalutamide, the most commonly-used anti-androgen, according to the company’s news releases. Unlike abiraterone, no steroids are necessary with MDV3100.