In a new study of patients with chronic kidney disease, the presence of kidney stones, compared with their absence, was significantly associated with a 2.3-fold increased risk of osteoporotic fracture

Kidney stones predict an increased risk of osteoporotic fracture in patients with chronic kidney disease (CKD), new data suggest.

“Despite previous reports that kidney stones were associated with higher risk of osteoporotic fracture, the association of kidney stones and osteoporotic fracture has not been established in patients with CKD … Our findings suggest that the presence of kidney stones should be considered as a clinical risk factor for osteoporotic fracture in patients with CKD,” investigators wrote in Scientific Reports.

A team led by Dong Ho Shin, MD, of Hallym University, Kandong Sacred Heart Hospital, Seoul, Korea, conducted a retrospective medical record-based study that included 2282 patients with stable stage 3–4 CKD who were treated from 2007 to 2017. Kidney stones developed in 113 patients. Investigators propensity score matched these patients with 113 patients without kidney stones.

During a mean follow-up period of 64.7 months, osteoporotic fractures occurred more frequently in patients with than without kidney stones (29.2% vs 14.2%). After adjusting for age, sex, body mass index, and other potential confounders, kidney stones were significantly associated with a 2.3-fold increased risk of osteoporotic fracture.

The authors acknowledged study limitations. Their study was retrospective, conducted at a single center, and based on a small number of CKD patients with kidney stones. In addition, they did not measure bone mineral density with dual-energy X-ray absorptiometry.

References

Han SG, Oh J, Jeon HJ, et al. Kidney stones and risk of osteoporotic fracture in chronic kidney disease. Sci Rep. 2019;9(1):1929. Published online ahead of print.

Older men with metastatic castration-resistant prostate cancer are often perceived as likely to play a passive role regarding care-related decisions.

A survey of Dutch multidisciplinary healthcare providers on the use of shared-decision making to facilitate treatment decisions in older men with metastatic castration-resistant prostate cancer (mCRPC) showed varying levels of agreement on the likely benefit of decision aids for these patients, as well as the need for clinician training to apply shared decision-making. The survey results were published in the Journal of Geriatric Oncology. 

Older men with metastatic castration-resistant prostate cancer are often perceived as likely to play a passive role regarding decisions related to their care. This study was designed to evaluate the attitudes of members of the multidisciplinary team (eg, oncologists, urologists, oncology nurses) on engaging these patients in the treatment decision process.

For the study, the authors drafted a 4-part survey adapted from similar studies focused on different diseases. Part 1 assessed demographic information on the healthcare provider; part 2 queried the healthcare providers on their opinions on involving older patients with mCRPC in treatment decisions, patients’ ability to evaluate the risks and benefits of particular treatments, and providers’ training in the application of shared decision-making; part 3 specifically addressed the opinions of healthcare providers on the use of decision aids with older patients with mCRPC; and part 4 asked healthcare providers to make specific treatment recommendations through presentation of 4 hypothetical cases  representative of this patient population. 

Of the 82 urologists, 31 oncologists, and 57 oncology nurses surveyed, 63% of urologists, 74% of oncologists and 65% of oncology nurses agreed that treatment decisions should ideally be made together with the patient. Interestingly, although more than 50% of oncologists and urologists expressed the opinion that physicians are inadequately trained in shared decision-making, only 20% of oncology nurses agreed that oncology nurses were not well trained in this area. With respect to use of a decision aid in this patient population, 45% of urologists, 32% of oncologists, and 56% of oncology nurses were in favor of its use. 

“Training healthcare providers on effective patient communication skills remains an imperative. Facilitating these conversations by making decision aid usage commonplace may better inform patients about treatments, associated risks, and expected prognosis, thus improving the decision-making process for both older patients and their healthcare providers,” wrote the authors.

Reference

de Angst IB, Kil PJM, Bangma CH, Takkenberg JJM.Should we involve patients more actively? Perspectives of the multidisciplinary team on shared-decision making for older patients with metastatic castration-resistant prostate cancer [published online January 10, 2019]. J Geriatr Oncol.doi: 10.1016/j.jgo.2018.12.003

Obese men treated with docetaxel for metastatic castration-resistant prostate cancer have longer cancer-specific and overall survival, a study found.

SAN FRANCISCO—Obesity is associated with improved cancer-specific and overall survival among men with metastatic castration-resistant prostate cancer (mCRPC) treated with docetaxel, investigators reported at the 2019 Genitourinary Cancers Symposium.

Alberto Martini, MD, of Icahn School of Medicine at Mount Sinai in New York, and collaborators identified 1577 patients with mCRPC from the control arms of 3 randomized trials (ASCENT2, MAINSAL, and VENICE). Study patients had a median age of 69 years and a median BMI of 28 kg/m². Of these patients, 655 died during follow-up. The median follow-up for survivors was 12 months.

Obesity, defined as a body mass index (BMI) greater than 30 kg/m², was associated with a significant 35% decreased risk of CSM and 29% decreased risk of death from any cause compared with patients who had a BMI of 25-30 kg/m² (reference), in adjusted analyses. Each 1 kg/m² increment in BMI was associated with a significant 6% decreased risk of cancer-specific mortality and 4% decreased risk of death from any cause. The patients found no interaction between BMI categories and docetaxel dose.

The investigators adjusted analyses for age, PSA level, number of metastases, prior treatment, and ECOG (Eastern Cooperative Oncology Group) performance status.

In a previous study published in 2018 in BJU International, investigators found that obesity was associated with a significant 21% decreased risk of all-cause mortality among men with non-metastatic CRPC compared with normal weight.

Reference

Martini A, Waingankar N, Brown NM et al. Obesity and metastatic castration resistant prostate cancer: Results from the control arms of ASCENT2, MAINSAL and VENICE trials. Data presented at the 2019 Genitourinary Cancers Symposium held in San Francisco, February 14-16. Abstract 287.

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Copyright © 2018 Haymarket Media, Inc. All Rights Reserved
This material may not be published, broadcast, rewritten or redistributed in any form without prior authorization.
Your use of this website constitutes acceptance of Haymarket Media’s Privacy Policy and Terms & Conditions.

By targeting prostate-specific membrane antigen, a molecule radiolabeled with lutetium-177 is expected to deliver high doses of beta radiation to distant metastases.

SAN FRANCISCO — Treatment with a novel targeted radiation therapy improves survival of men with metastatic castration-resistant prostate cancer (mCRPC), according to the findings of a study presented at the 2019 Genitourinary Cancers Symposium.¹

The therapy consists of a small molecule that has a high affinity for prostate-specific membrane antigen (PSMA) that is radiolabeled with lutetium-177. The therapy, called lutetium-177 PSMA-617 (LuPSMA), purportedly delivers high doses of beta radiation to cancer metastases.

In a phase 2 trial that included 50 men with mCRPC who progressed despite treatment with standard therapies, the median overall survival times was 13.3 months (95% confidence interval [CI], 10.5–18.0), which is longer than the average 9-month survival time for men with this stage of disease, according to investigators. Survival time was significantly longer among patients who had a PSA decrease of 50% or more compared with those who had a smaller PSA decrease (18.0 vs 8.7 months). Median PSA progression-free survival was 6.9 months (95% CI, 6.0–8.7).

A 50% or greater decline in PSA was achieved in 32 of 50 patients (64%; 95% CI, 50%–77%), including 22 patients (44%; 95% CI, 30%–59%) who experienced a PSA decline of 80% or more. The most common toxicities attributed to treatment were transient G1-2 dry mouth in 68% of patients, G1-2 nausea in 48%, and G1-2 fatigue in 36%. G3-4 toxicities attributed to the treatment were infrequent, with thrombocytopenia in 10% of patients, and anemia in 10%.

“In this trial, we treated men who would have otherwise been directed to palliative care,” lead investigator Michael Hofman, MBBS, of the Peter MacCallum Cancer Centre in Melbourne, Australia, said in a statement prepared by the conference organizers.²

The study participants received prior docetaxel (84%), cabazitaxel (48%), and abiraterone acetate and/or enzalutamide (90%). The median PSA doubling time was 2.6 months.

The investigators previously reported favorable activity and toxicity with LuPSMA in a study of 30 patients with mCRPC.

“The results of this 50-patient study provide further confidence to our previously published 30-patient study, demonstrating high response rates and low toxicity in men with metastatic castration-resistant prostate cancer who have progressed after conventional therapies,” Dr Hofman said in a presscast held in advance of the conference, which is sponsored by the American Society of Clinical Oncology (ASCO), Society of Urologic Oncology (SUO), and the American Society for Radiation Oncology (ASTRO).

“As a clinician, I will tell you that this is a very intriguing agent,” commented Robert Dreicer, MD, MS, an expert spokesperson from the American Society of Clinical Oncology (ASCO), who moderated the presscast.

Two randomized controlled trials of LuPSMA are under way: the ANZUP/Prostate Cancer Foundation of Australia TheraP trial (177Lu-PSMA-617 vs cabazitaxel) (ClinicalTrials.gov Identifier: NCT03392428) and the Endocyte VISION trial (177Lu-PSMA-617 vs best standard of care) (ClinicalTrials.org Identifier: NCT03511664).

Read more of Cancer Therapy Advisor‘s coverage of the 2019 Genitourinary Cancers Symposium by visiting the conference page.

References

1. Hofman M, Violet JA, Hicks RJ, et al. Results of a 50 patient single-centre phase II prospective trial of lutetium-177 PSMA-617 theranostics in metastatic castrate-resistant prostate cancer. Data presented at: the 2019 Genitourinary Cancers Symposium; San Francisco, CA; February 14-16, 2019. Abstract 228.
2. American Society of Clinical Oncology (ASCO). Phase II trial shows novel, radiolabeled PSMA-targeted treatment provides high response rates in men with metastatic prostate cancer [press release]. Published February 11, 2019. Accessed February 11, 2019.

After an additional 1 year of follow-up, apalutamide plus ADT continued to show a significant decrease in the risk of progression to metastasis or death.

An updated analysis of patients in the SPARTAN trial showed that apalutamide continues to demonstrate benefit for patients with high-risk nonmetastatic castration-resistant prostate cancer (nmCRPC), according to findings presented at the 2019 Genitourinary Cancers Symposium.

SPARTAN is a phase 3 multicenter, randomized, double-blind trial that enrolled 1207 patients with nmCRPC who had a prostate-specific antigen (PSA) doubling time of 10 months or less. Investigators randomly assigned 806 patients to receive apalutamide plus androgen deprivation therapy (ADT) and 401 to receive placebo plus ADT. The primary analysis, which was conducted 1 year ago, showed that apalutamide decreased the risk of distant metastases or death (metastasis-free survival [MFS]) by 72% compared with placebo.

The updated analysis, conducted by Eric J Small, MD, of the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, and collaborators, looked at second progression-free survival (PFS2) — defined as the time from randomization, through the development of metastases,  until disease progression on subsequent anticancer therapy or death — and safety after 1 year of additional follow-up. The median treatment duration with apalutamide and placebo was 25.7 months and 11.5 months, respectively. (In the original analysis, the median treatment duration was 19.2 and 11.2 months, respectively.)

Compared with the placebo group, the apalutamide group had a significant 50% decreased risk of PFS2 (hazard ratio [HR] 0.5; 95% CI, 0.39-0.63; P <.0001). The median time to PFS2 was not reached in the apalutamide arm and was 39.3 months among placebo recipients.

“These data suggest that earlier treatment, prior to the development of overt metastases, is likely to provide an advantage over delaying therapy until metastases develop,” Dr Small said in an interview with Cancer Therapy Advisor.

In addition, at a median follow-up of 32 months, 51.3% of patients in the apalutamide group, 8% of the 75 patients who crossed over from the placebo to the apalutamide group, and 99.7% of remaining placebo recipients had discontinued study treatment.

Rates of discontinuation due to progressive disease and adverse events (AEs) were 27.3% and 12.7%, respectively, in apalutamide-treated patients and 73.4% and 8.4%, respectively, in the placebo arm. Dr Small’s team found no substantial change in the incidence of treatment-emergent AEs in the apalutamide group at the 1-year update, despite a longer exposure time to apalutamide.

With respect to drug-related treatment-emergent AEs, the investigators reported no grade 4 or 5 events. Grade 3 treatment-emergent AEs included rash (5.2%), falls (2.4%), and fractures (3.1%).

Read more of Cancer Therapy Advisor‘s coverage of the 2019 Genitourinary Cancers Symposium by visiting the conference page.

Reference

1. Small EJ, Saad F, Chowdhury S, et al. Updated analysis of progression-free survival with first subsequent therapy (PFS2) and safety in the SPARTAN study of apalutamide (APA) in patients (pts) with high-risk nonmetastatic castration-resistant prostate cancer (nmCRPC). Data presented at: 2019 Genitourinary Cancers Symposium; San Francisco, CA; February 14-16, 2019. Abstract 144.

The Decipher genomic classifier predicted metastases and prostate cancer-specific mortality following radical prostatectomy with greater precision in African-American men.

SAN FRANCISCO — Decipher, a genomic test for prostate cancer (PCa), may predict poor disease-specific outcomes more accurately in African-American men (AAM) than in European-American men (EAM), new study findings presented at the 2019 Genitourinary Cancers Symposium suggest.

Using Decipher, a team led by Stephen J. Freedland, MD, who is affiliated with Cedars-Sinai Medical Center in Los Angeles and has a joint appointment at the Durham VA Health Care System in Durham, North Carolina, calculated genomic classifier (GC) scores for 554 men with PCa (306 AAM and 239 EAM) who underwent radical prostatectomy (RP) at the VA medical center from 1989 to 2016. 

The study population was a clinically high-risk cohort, with patients having either stage T3a disease, positive surgical margins, seminal vesicle invasion, or who had received post-RP radiation. Dr Freedland and his colleagues compared GC score and Cancer of the Prostate Risk Assessment score (CAPRA-S) with respect to their ability to predict metastasis and PCa-specific mortality (PCSM).

With a median follow-up of 9 years, metastases developed in 40 patients and 18 died from PCa. Among the African-American patients, 154 (50%) were deemed low risk by Decipher and 218 (71%) were determined to be low/intermediate risk by CAPRA-S measures.

On multivariable analysis, GC score (hazard ratio [HR] 1.30; 95% confidence interval [CI], 1.01–1.69; P =.044) and CAPRA-S (HR 1.27; 95% CI, 1.01–1.58; P =.037) significantly predicted metastasis in the EAM patients. Among AAM patients, GC score (HR 1.70; 95% CI, 1.31–2.20; P <.001), but not CAPRA-S, significantly predicted metastasis. 

In both EAM (HR 1.54; 95% CI, 1.01–2.53; P =.044) and AAM (HR 1.65; 95% CI, 1.19–2.42; P =.002), GC score, but not CAPRA-S, significantly predicted PCSM. GC score had greater accuracy for predicting these outcomes in AAM. GC score predicted metastasis and PCSM 8 years after RP with 84% and 82% accuracy, respectively, in the AAM patients compared with 70% and 73% in the EAM patients, respectively.

“These data add to the growing data that Decipher is a robust measure of clinical outcomes across many cohorts and many disease settings,” Dr Freedland said. “To that we can now add that Decipher predicts outcomes regardless of race, which is important given black men are at the highest risk of aggressive prostate cancer in the world. The fact that Decipher appeared to work even better in black men is intriguing and deserves further study and may underlie some genomics differences by race that we are continuing to evaluate.”

Disclosure: The study was funded by GenomeDx Biosciences, the maker of Decipher.

Read more of Cancer Therapy Advisor‘s coverage of the 2019 Genitourinary Cancers Symposium by visiting the conference page.

Reference

1. Freedland SJ, du Plessis M, Zhang I, et al. A genomic classifier shows improved prediction of oncologic outcomes in African-American men treated with radical prostatectomy. Presented at: the 2019 Genitourinary Cancers Symposium; San Francisco, CA; February 14-16, 2019. Abstract 8.

The study is the first to show that treatment with abiraterone acetate/enzalutamide is associated with better survival in African American patients with mCRPC compared with Caucasians.

SAN FRANCISCO — Abiraterone acetate or enzalutamide treatment for metastatic castration-resistant prostate cancer (mCRPC) in chemotherapy-naive patients is associated with better overall survival (OS) in African American men compared with white men, investigators reported at the 2019 Genitourinary Cancers Symposium.

The study provides the first evidence that African American men with mCRPC have better OS than white men treated with either abiraterone acetate or enzalutamide, according to a team led by Megan Ann McNamara, MD, of Duke University School of Medicine in Durham, North Carolina.

In a retrospective study of 2123 white men and 787 black men with mCRPC, Dr McNamara and her colleagues found that the median OS time was 30 months for African Americans compared with 26 months for whites. African Americans had a significant, 17.4% decreased risk of death compared with whites, after adjusting for age and comorbidities (hazard ratio [HR]=0.826; 95% CI [0.732-0.933]; P =.0020).

“When controlling for access to care through a single-payer system, in this case the VA health system, in chemotherapy-naive metastatic castration-resistant prostate cancer patients, African Americans may have better overall survival than Caucasians when treated with abiraterone acetate or enzalutamide,” Dr McNamara said.

The findings reinforce what is already the standard of care, she said. “It’s important that we have real-world studies that show that the standard-of-care treatments really work,” Dr McNamara said. “I don’t think they necessarily change what we’re doing, but they reinforce what we are already doing.”

The mean ages of the white and African American men were 74 and 71 years, respectively. The median follow-up time was 561 days and 570 days for whites and African Americans, respectively.

African American men were more likely than white men to have type 2 diabetes (38.1% vs 29.3%; P <.0001), hypertension (77.1% vs 67.1%; P <.0001), and liver damage or abnormality (8.8% vs 5.2%; P =.0003)

Read more of Cancer Therapy Advisor‘s coverage of the 2019 Genitourinary Cancers Symposium by visiting the conference page.

Reference

1. McNamara MA, George DJ, Ramaswamy K, et al. Overall survival by race in chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate or enzalutamide. Data presented at: the 2019 Genitourinary Cancers Symposium; San Francisco, California; February 14-16, 2019. Abstract 212.

Median metastasis-free survival was longer with darolutamide than with placebo: 40.4 vs 18.4 months.

Darolutamide, a new androgen-receptor antagonist, prolongs survival without metastases in men with nonmetastatic castration-resistant prostate cancer (CRPC) and a PSA doubling time of 10 months or less. Karim Fizazi, MD, of the Universite Paris-Sud in France, and colleagues reported the new findings in the New England Journal of Medicine.

In the phase 3 ARAMIS (Androgen Receptor Antagonizing Agent for Metastasis-free Survival) trial, investigators randomly assigned 1509 CRPC patients without metastases from 36 countries 2:1 to darolutamide (600 mg twice daily with food) or placebo. Meanwhile, patients continued taking androgen deprivation therapy (luteinizing hormone-releasing hormone agonist or antagonist).

Darolutamide recipients had longer median metastasis-free survival by 22 months compared with placebo recipients: 40.4 vs 18.4 months. Risk for metastasis or death significantly declined by 59% in the intervention group, including for patients with lower-risk PCa. Patients taking darolutamide also experienced significant delays to pain progression, cytotoxic chemotherapy, and symptomatic skeletal events by 35%, 57%, and 57%, respectively. With respect to secondary endpoints, overall survival improved by 29%, whereas progression-free survival, and times to PSA progression, invasive procedure, or antineoplastic therapy significantly improved by 62%, 87%, 61%, and 67%, respectively.

Darolutamide, a nonsteroidal androgen-receptor antagonist with 2 pharmacologically active diastereomers, is structurally distinct from other androgen-receptor inhibitors, Dr Fizazi and the team explained. By comparison, median metastasis-free survival was 36.6 months with enzalutamide in the PROSPER trial and 40.4 months with apalutamide in the SPARTAN trial.

Darolutamide showed good safety. Unlike the enzalutamide and apalutamide trials, fatigue and asthenia were less common. Hypertension, adverse effects related to central nervous system, falls, and fracture also were no more common with the drug than with placebo. The investigators believe darolutamide has low penetration of the blood-brain barrier. Overall, 24.8% of the darolutamide group and 20% of the placebo group experienced a serious adverse event, and 3.9% vs 3.2% experienced a Grade 5 event. Quality of life was similar for both groups. Similar proportions of the darolutamide and placebo groups discontinued their regimens: 8.9% vs 8.7%.

“These results confirm the benefits of early and potent inhibition of androgen-receptor signaling in patients with nonmetastatic, castration-resistant prostate cancer…” Dr Fizazi and the team stated. “In the current trial, darolutamide treatment did not adversely affect quality of life, and it resulted in delayed occurrence of metastases with a favorable safety profile.”

Men of African ancestry were underrepresented in the trial, so no conclusions can be made for this population. In addition, use of life-prolonging therapy in placebo patients who developed metastases potentially affected secondary results.

The ARAMIS study was funded by Bayer HealthCare and Orion Pharma, developers of darolutamide.

Reference

Fizazi K, et al. Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer (ARAMIS). N Engl J Med. DOI:10.1056/NEJMoa1815671