“Patients who received hormonal regimens for the treatment of castration-resistant prostate cancer experienced a significant increase in incidence of and relative risk for cardiovascular toxicity, according to results of a meta-analysis.
“Roberto Iacovelli, MD, medical oncologist in the division of urogenital and head and neck tumors at European Institute of Oncology in Milan, and colleagues sought to define the incidence and RR of cardiovascular events in a population of patients treated with new hormonal therapies for metastatic castration-resistant prostate cancer.
“Incidence of all-grade toxicities (grades 1-4) and high-grade toxicities (grade 3-4) served as the primary outcome of the study.
“Iacovelli and colleagues identified six prospective phase 2 or phase 3 studies that included a total of 7,830 patients. Within each study, researchers considered treatment with a novel hormonal agent plus prednisone in the experimental arm (n = 4,520) and placebo plus prednisone (n = 3,310) as the control.”
“Fred Saad, MD, FRCS, professor, Department of Surgery, University of Montreal, discusses the use of radium-223 for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC).
“The approved indication for radium-223 is in patients with metastatic disease to the bone, but no visceral disease. Patients should also demonstrate symptoms, though they do not need to be in significant pain, Saad explains. If patients wait too long to seek treatment, they are less likely to receive all six cycles of treatment and the added survival benefit.
“Researchers have not witnessed negative effects associated with administering radium-223 into earlier lines of therapy, Saad says. Compared with other treatments, few adverse events occurred with radium-223 in the international early access program. The treatment is also said to be well-tolerated regardless of disease stage.”
“For more than a decade, oncologists using cytotoxic chemotherapy to treat patients with advanced metastatic castration-resistant prostate cancer (mCRPC) have relied on the sequential use of single agent taxanes such as docetaxel and cabazitaxel. For example, docetaxel is commonly used as the ‘first-line’ therapy, while cabazitaxel is used as the ‘second-line’ therapy. A role for combination therapy using two or more chemotherapy agents at the same time has not been well studied. This week, however, results of a clinical trial presented at the American Society of Clinical Oncology meeting by researchers at The University of Texas MD Anderson Cancer Center may change the perspective on a role for combination chemotherapy in advanced disease.
“The study compared the effectiveness of cabazitaxel alone versus cabazitaxel combined with carboplatin – a type of platinum chemotherapy—in patients with metastatic castrate-resistant prostate cancer (mCRPC). To date, 160 men have been randomized to treatment with either the single or dual chemotherapy drug regimen. Each patient received up to 10 cycles of chemotherapy.
“Innocrin Pharmaceuticals, Inc., a clinical-stage pharmaceutical company developing small-molecule CYP17 lyase-selective inhibitors for the treatment of hormonally-dependent breast and prostate cancers resistant to standard hormonal therapy, today announced the initiation of a new Phase 2 study: Once-daily Oral VT-464 in Patients With CRPC Progressing on Enzalutamide or Abiraterone (clinicaltrials.gov/ct2/show/NCT02445976). The trial is led by Howard Scher, MD, Chief of Genitourinary Oncology Service at Memorial Sloan Kettering, who is the recipient of a prestigious $1 million Challenge Award from the Prostate Cancer Foundation (PCF). Dr. Scher is a recognized leader of a ‘personalized medicine’ approach for CRPC, the goal being to deliver the right drug to patients at the right time.”
“The PREVAIL trial showed that enzalutamide (Xtandi) improved overall survival and progression-free survival vs placebo in asymptomatic/minimally symptomatic chemotherapy-naive patients with metastatic castration-resistant prostate cancer. In analyses reported in The Lancet Oncology, Loriot et al found that enzalutamide treatment was associated with improved patient-reported outcomes and an increased time to first skeletal-related event in the trial.
“In the double-blind trial, patients were randomly assigned to receive enzalutamide 160 mg/d (n = 872) or placebo (n = 845). Health-related quality of life was assessed at baseline and during treatment using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) and EuroQol-5 dimension (EQ-5D) questionnaires. Pain status was assessed at screening, baseline, week 13, and week 25 with the Brief Pain Inventory Short Form (BPI-SF).
“Significant between-treatment differences in change from baseline to week 61 for enzalutamide vs placebo were observed for most FACT-P endpoints and the EQ-5D visual analog scale. Median time to deterioration in FACT-P total score was 11.3 months vs 5.6 months (hazard ratio [HR] = 0.62, P < .0001). Clinically meaningful improvements were observed for the FACT-P total score in 40% vs 23%, for the EQ-5D utility index in 28% vs 16%, and for the EQ-5D visual analog scale in 27% vs 18% (P < .0001 for all comparisons)…
“The investigators concluded: ‘In addition to improving overall survival relative to placebo, enzalutamide significantly improves patient-related outcomes and delays occurrence of first skeletal-related event in chemotherapy-naive men with metastatic castration-resistant prostate cancer.’ ”
“In a randomized phase II trial (SWOG S0925) reported in the Journal of Clinical Oncology, Yu et al found that the addition of cixutumumab to androgen-deprivation therapy did not significantly increase the rate of undetectable prostate-specific antigen (PSA) in patients with newly diagnosed metastatic hormone-sensitive prostate cancer. Cixutumumab inhibits the insulin-like growth factor I receptor (IGF-IR).
“In the study, 210 patients from SWOG institutions were randomly assigned between February 2011 and December 2012 within 30 days of starting androgen deprivation to receive bicalutamide daily with a luteinizing hormone-releasing hormone agonist alone (n = 105) or with cixutumumab at 10 mg/kg given intravenously over 1 hour every 2 weeks for seven 28-day cycles. The primary endpoint was rate of undetectable PSA (≤ 0.2 ng/mL) at 28 weeks.
“The cixutumumab and control groups were generally balanced for baseline characteristics, including age (median, 65 and 66 years), PSA level (median, 31 and 37 ng/mL), Gleason score (≥7 in 60% and 78%), race (89% and 84% white), metastasis site (lymph node only in 14% and 9%, bone only in 53% and 60%, both in 18% and 16%, visceral in 14% and 15%), and early-induction androgen deprivation (56% and 62%).”
“Topline results announced today from the phase III Swedish trial 10TASQ10 demonstrated that tasquinimod failed to extend overall survival (OS) in men with metastatic castrate-resistant prostate cancer (mCRPC; HR=1.09; CI 95%, 0.94-1.28). The findings prompted the manufacturers, Active Biotech and Ipsen, to discontinue all studies in prostate cancer involving the agent, according to a joint statement.
“Previously, OncLive reported on the results of a phase II trial that showed a prolonged progression-free survival (PFS) and OS with tasquinimod in certain men with mCRPC.1 Men in that trial were followed for a median of 37 months. At the time, researchers suggested the agent may provide a survival advantage in this setting, particularly among men with skeletal metastases.
“ ‘The outcome of the 10TASQ10 study is a major disappointment based on the promising phase II results,’ Tomas Leanderson, president and chief executive officer of Active Biotech said in a statement. ‘However, the data at hand are unambiguous and cannot motivate further development of tasquinimod in this patient population.’
“Although the antiangiogenic agent did not improve OS, it did reduce the risk of radiographic cancer progression or death compared to placebo (HR = 0.69; 95% CI, 0.60-0.80). Full results will be presented at an upcoming scientific conference.”
“In an analysis reported in the Journal of Clinical Oncology, Scher et al found that circulating tumor cell count and LDH level served as an individual-level surrogate for survival among patients with metastatic castration-resistant prostate cancer receiving abiraterone acetate (Zytiga) plus prednisone vs prednisone in the phase III COU-AA-301 trial.
“The double-blind COU-AA-301 trial included 1,195 patients previously treated with paclitaxel. The current analysis includes 711 patients (484 in the abiraterone-prednisone group, 227 in the prednisone group) with available 12-week biomarker data. Biomarker analysis was a secondary objective of the trial.
“The combination of circulating tumor cell count and LDH level at 12 weeks was shown to satisfy the four Prentice criteria for individual-level surrogacy (ie, treatment must have a significant effect on the clinical endpoint and a significant effect on the biomarker, the biomarker must have a significant impact on the endpoint, and the full effect of treatment on the endpoint must be captured by the biomarker)…
“The investigators concluded: ‘A biomarker panel containing [circulating tumor cell] number and LDH level was shown to be a surrogate for survival at the individual-patient level in this trial of abiraterone acetate plus prednisone versus prednisone alone for patients with metastatic [castration-resistant prostate cancer]. Additional trials are ongoing to validate the findings.’ ”
“Patients with castration-resistant prostate cancer treated with enzalutamide demonstrated significantly longer PFS than those treated with bicalutamide, according to topline results of the phase 2 STRIVE trial released by Astellas.
“The trial included 396 patients with castration-resistant prostate cancer. About two-thirds of the patients (n = 257; 64.8%) had metastatic disease. The other 139 patients had nonmetastatic disease that progressed after surgical castration or treatment with a luteinizing hormone-releasing hormone analogue therapy.
“Researchers randomly assigned patients to 160 mg once-daily enzalutamide (Xtandi; Astellas, Medivation) — an androgen receptor antagonist — or 50 mg once-daily bicalutamide, an oral non-steroidal antiandrogen. PFS served as the primary endpoint.
“Patients assigned enzalutamide demonstrated a significant improvement in median PFS (19.4 months vs. 5.7 months; HR = 0.24; 95% CI, 0.18-0.32), according to a press release issued by Astellas. Median time on treatment also was longer in the enzalutamide group (14.7 months vs. 8.4 months).”