“The use of bipolar androgen therapy (BAT), involving rapid cycling between high and low serum concentrations, was safe and resulted in responses and resensitization to enzalutamide in men with metastatic castration-resistant prostate cancer (CRPC) who progressed after initial enzalutamide therapy, according to a new study.
“ ‘Clinically, metastatic CRPC that has progressed after enzalutamide treatment is minimally responsive to further therapy that inhibits androgen receptor signaling,’ wrote study authors led by Benjamin A. Teply, MD, of Johns Hopkins School of Medicine in Baltimore. ‘Theoretically, rapidly varying the androgen concentrations between the extremes of supraphysiological and near-castrate, a strategy termed BAT, provides insufficient time for CRPC cells to adaptively regulate androgen receptor concentrations,’ and thus may promote cancer cell death and prevent resistance.”
“Although modern immunotherapy has yet to have a breakthrough in prostate cancer to the degree it has had in lung cancer or urothelial carcinoma, combinations with anti–PD-1/PD-L1 agents are beginning to show promise for these patients in clinical trials.
“Currently ongoing is a phase II trial of durvalumab (Imfinzi) in combination with the PARP inhibitor olaparib (Lynparza) in patients with metastatic castration-resistant prostate cancer (mCRPC; NCT02484404). Investigators note that previous data have suggested that 25% to 30% of sporadic mCRPC has DNA-repair pathway defects. Results thus far have demonstrated that the synergy of durvalumab and olaparib proves that the combination may be a viable option for patients with mCRPC who are heavily pretreated. The trial is still accruing.”
“According to results of a phase I/II study, men with metastatic castration-resistant prostate cancer (mCRPC) who received a second course of radium-223 (Xofigo) experienced minimal hematologic toxicity and low radiographic bone progression rates.
“In the study, 29 of 44 patients (66%) received the full course of 6 injections. Median time to total alkaline phosphatase was not reached. Median time to PSA progression was 2.2 months.”
“Therapy options are limited for men with advanced-stage, metastatic castration-resistant prostate cancer (mCRPC), but a new treatment protocol offers hope. In the featured article of The Journal of Nuclear Medicine‘s October issue, German researchers report on their recent clinical experience, which establishes a dosing regimen for actinium-225 (225Ac)-labeled targeted alpha therapy of patients with prostate specific membrane antigen (PSMA)-positive tumors. The protocol balances treatment response with toxicity concerns to provide the most effective therapy with the least side effects.”
“Prostate cancer researchers are continuing to explore strategies to optimally integrate bone-targeted agents into patient care.
“For example, an ongoing trial is assessing the combination of a radiopharmaceutical, radium-223 dichloride (Xofigo), with an androgen receptor-directed therapy, either abiraterone acetate (Zytiga) or enzalutamide (Xtandi). The open-label, phase IIa study is accruing patients with metastatic castration-resistant prostate cancer (mCRPC). The primary endpoint of the trial, which hopes to enroll 68 patients, is patient bone scan response rate (NCT02034552).”
“In the phase III CA184-095trial reported in the Journal of Clinical Oncology, Tomasz M. Beer, MD, FACP, of the Knight Cancer Institute, Oregon Health and Science University, and colleagues found that ipilimumab (Yervoy) did not increase overall survival vs placebo in men with asymptomatic or minimally symptomatic chemotherapy-naive metastatic castration-resistant prostate cancer without visceral metastases. Ipilimumab was associated with prolonged progression-free survival and a higher prostate-specific antigen (PSA) response rate.”
“Metformin use in combination with docetaxel chemotherapy does not significantly improve survival in patients with diabetes and metastatic castration-resistant prostate cancer, according to a study published in the April issue of The Journal of Urology.
“Michelle J. Mayer, from Sunnybrook Health Sciences Centre in Toronto, and colleagues used data from several Ontario administrative health care databases to identify men (older than 65 years) diagnosed with metastatic castration-resistant prostate cancer and treated with docetaxel. Patients were stratified into groups based on diabetes status and use of antidiabetic medications to assess the effect of metformin use with docetaxel on survival.”
“There has been a lot of buzz recently about the use of ‘liquid biopsies’ and how these blood tests that show cancer may be able to replace the need for tissue biopsies.
“The latest study shows that such a test could be useful in metastatic prostate cancer, where the biopsy sample would need to be taken from bone, which is painful, risky, and expensive, says an expert.
“This study used the Guardant360 test and found that cell-free, circulating tumor DNA (ctDNA) was detected in most patients (94%) with metastatic castration-resistant prostate cancer (mCRPC).”
“As oncologists await future treatment advances in metastatic castration-resistant prostate cancer (mCRPC), the key is to unleash the full potential of available therapies, Robert Dreicer, MD, asserted during the 2016 CFS Chemotherapy Foundation Symposium.
“One agent that oncologist are focused on optimizing, Dreicer said, is radium-223 (Xofigo). Optimal use of this treatment remains mostly unknown, with current efforts focusing on exploring the agent’s potential in combination regimens.
“For instance, a phase III trial is randomizing patients with bone predominant mCRPC to radium-223 plus abiraterone acetate (Zytiga) or abiraterone alone (NCT02043678). Additionally, a randomized phase IIa study is evaluating the efficacy and safety of radium-223 in combination with abiraterone or enzalutamide (Xtandi) in patients with mCRPC to investigate bone-scan response, radiological progression-free survival, overall survival, and skeletal events (NCT02034552).”