“Detection of circulating tumor cells (CTCs) positive for the nuclear-specific AR-V7 protein was an independent predictor of shortened progression-free survival (PFS) and overall survival (OS) when treating metastatic castration-resistant prostate cancer (mCRPC) with abiraterone or enzalutamide, according to results of the PROPHECY study (abstract 5004). The findings were presented at the 2018 Annual Meeting of the American Society of Clinical Oncology (ASCO), held June 1–5 in Chicago.
“’Men with AR-V7–positive CTCs have a very low probability of benefit from abiraterone or enzalutamide, ranging from 0% to 11%,’ said Andrew J. Armstrong, MD, of Duke Cancer Institute. ‘However, a lack of AR-V7 detection does not guarantee response or benefit’ where these therapies are concerned, he added.”
“Black men with metastatic castration-resistant prostate cancer (CRPC) who received hormonal therapy with the adrenal inhibitor abiraterone had greater and longer-lasting responses compared with white men, according to the results of a late-breaking study (abstract LBA5009) presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, held in Chicago June 1–5.
“The prospective study found that black men were more likely to have a decline in prostate-specific antigen (PSA) and had a longer median time to PSA worsening than white men. The findings were presented by Daniel George, MD, professor of medicine and surgery at Duke University.”
“Updated results from the phase II LuPSMA study published in The Lancet Oncology showed radionuclide treatment with Lutetium-177 [177Lu]-PSMA-617 nearly doubled median PSA progression-free survival (PFS) in men with progressive metastatic castrate-resistant prostate cancer (mCRPC) compared with previous results with another radiopharmaceutical, radium-223 (Ra-223; Xofigo).
“In LuPSMA, the median PSA PFS was 7.6 months (95% CI, 6.3-9.0) and 27 (90%) of 30 men experienced PSA progression. The median overall survival (OS) was 13.5 months (95% CI, 10.4-22.7) and 22 (73%) men had died by the November 2017 data cutoff.”
“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.”