SAN FRANCISCO—Physicians have seen their pharmaceutical options for treating advanced prostate cancer expand substantially in the past decade. In the years since these new medications received FDA approval and entered the marketplace, researchers have been evaluating the safety and efficacy and prescribing of these drugs in the more varied population of patients seen in clinical practice than in the clinical trials that led to approval of the drugs. Such real-world studies presented at the 2020 Genitourinary Cancers Symposium have found that the performance of these newer treatments generally are in line with clinical trial findings but also have revealed new information about treatment efficacy and provide a snapshot of how doctors are using the therapies in routine clinical practice.
“These studies really help reinforce the translation of randomized clinical trial data to clinical care,” said symposium attendee Tanya B. Dorff, MD, a medical oncologist who is head of genitourinary cancers at City of Hope, a comprehensive cancer center in Duarte, California. “The clinical trials can tell us success rates in a select population, but they cannot tell us how those are translating into clinical practice. Almost always it seems like people are practicing differently than what data might suggest is recommended, and patients aren’t getting as many lines of therapy as we might hope they would.”
Clinical trials leading to approvals of the newer therapies for advanced genitourinary cancers compared the treatments with placebo. Real-world studies, however, have enabled researchers to evaluate the performance of different agents in clinical practice, Dr Dorff said. She cited as an example a study by Rana R. McKay, MD, of Moores Cancer Center at the University of California, San Diego, and colleagues, who used Medicare claims data to examine the effect of sipuleucel-T on survival among 6125 men with metastatic castration-resistant prostate cancer (mCRPC).
Dr McKay’s team found that men who received sipuleucel-T—an autologous cellular immunotherapy approved in 2010 for treating asymptomatic or minimally symptomatic mCRPC—at any point in their therapeutic continuum experienced a significant 45% decreased risk of death and lived a median of 14.5 months longer than men who received only abiraterone or enzalutamide, Dr McKay’s team reported in a poster presentation at the symposium. In the setting of first-line treatment, recipients of sipuleucel-T had a 43% lower risk of death than patients treated only with abiraterone or enzalutamide. Median survival was 14 months longer for the sipuleucel-T group than the recipients of only abiraterone or enzalutamide. Analyses did not adjust for potential confounding variables.
“We believe these findings have revealed the importance of using treatments with complementary [mechanisms of action] to maximize patient survival outcomes,” Dr McKay said.
Some studies presented at the symposium characterize how physicians today use the newer agents in sequence. A separate retrospective institutional study by Dr McKay and colleagues demonstrated wide variation in the use of radium-223, a bone-seeking radioactive isotope that emits alpha particle radiation that was approved in 2013 for use in men who have mCRPC with bone metastases. Of 220 men treated with radium-223 at Dana-Farber Cancer Institute in Boston, 64 received the drug prior to chemotherapy, 83 received it after chemotherapy, and 73 received no chemotherapy. The most commonly observed treatments used in combination with radium-223 were enzalutamide (52.2%) and abiraterone (43.5%).
And in a study of patients receiving care for advanced prostate cancer at Veterans Affairs medical centers, a team led by Stephen J. Freedland, MD, of the Center for Integrated Research in Cancer and Lifestyle at Cedars-Sinai Medical Center in Los Angeles, found that sequential use of one androgen-receptor (AR) targeted agent (abiraterone or enzalutamide) after another was common despite new evidence that such back-to-back use of AR-targeted agents is associated with relatively low efficacy in certain scenarios. Among 32 men who received abiraterone for metastatic castration-sensitive prostate cancer, 25 (78%) received enzalutamide as their first-line treatment after progressing to mCRPC. Among 208 men whose disease progressed to mCRPC after receiving docetaxel, 196 (94%) received an AR-targeted agent as first-line therapy. Of the 113 who went on to receive a second line mCRPC drug, 70 (62%) received an AR-targeted agent again.
In a separate study of 931 chemotherapy-naïve men with mCRPC treated at private urology practices in the United States, Dr Freedland and colleagues found that the median baseline PSA at enzalutamide initiation was much lower in their cohort than in the patients in the randomized phase 3 PREVAIL trial (9 vs 54.1 ng/mL). The lower PSA at enzalutamide initiation could explain the longer time to PSA progression found in their study compared with the PREVAIL trial (median 18.5 vs 11.2 months). It might be that doctors are prescribing the drug earlier in the disease course than in the clinical trial, Dr Freedland said.
In addition, unlike the PREVAIL trial, the study by Dr Freedland’s group found that a lower proportion of their study patients had PSA reductions of 50% or more and 90% or more, “which may be attributed to more frequent PSA monitoring within a clinical trial setting and, thus, more opportunity to capture the true best PSA response,” they reported in a poster presentation.
As for why the use of medications might differ in real-world practice, Dr Dorff speculated that patient preferences might be a factor. For example, even when patients with mCRPC are informed that back-to-back use of AR-targeted agents would likely be less effective than moving on to chemotherapy, they may opt for the sequential AR-targeted therapy because they are concerned about the potential impact of chemotherapy on their quality of life, Dr Dorff said.