In an open-label trial, 93% of Black men with metastatic hormone-sensitive prostate cancer (mHSPC) experienced a response to treatment with enzalutamide; the response rate was nearly identical to the 94% response rate among non-Black men.
The finding is important because it shows that Black men, who historically have been underrepresented in prostate cancer studies but who constituted 41% of the current trial, also benefit from newer treatments.
Seventy-one men with mHSPC were randomly assigned in a 1:1 ratio to receive either enzalutamide 160 mg daily or bicalutamide 50 mg daily. Enzalutamide is a recently approved second-generation androgen receptor blocker; bicalutamide is a first-generation blocker that was approved in 1995. Patients who received either drug had undergone testosterone suppression with a luteinizing hormone–releasing hormone analogue.
Overall, 30 of 32 patients who received enzalutamide (94%) met the primary endpoint by achieving a prostate-specific antigen (PSA) level <4 ng/mL after 7 months. That endpoint was a surrogate of overall survival. Of the patients who received bicalutamide, 17 of 26 men (65%) met the primary endpoint (P = 0.008). PSA wasn't measured at 7 months for the remaining 13 men.
Enzalutamide is one of several newer androgen receptor axis–targeting (ARAT) agents. The benefit of enzalutamide in comparison with bicalutamide has been demonstrated before in phase 3 trials, but almost exclusively in White men. In the new trial, 29 men (41%) were Black; the other patients were White, and there was one Asian man in the four-center study.
"To our knowledge, this is the only randomized clinical trial comparing bicalutamide with enzalutamide in a Black patient population.... The favorable risk benefit profile makes it crucial to strongly consider the addition of enzalutamide to ADT [androgen deprivation therapy] in Black patients with mHSPC," say the investigators, led by genitourinary oncologist Ulka Vaishampayan, MD, professor at the University of Michigan, Ann Arbor, Michigan.
The trial was reported in JAMA Open Network.
Differences in Black and White
Importantly, only 42% of Black men experienced a response to bicalutamide; 93% of those patients experienced a response to enzalutamide, the newer agent. Among non-Black patients, the response to the older agent was more comparable ― 86%, vs 94% with enzalutamide.
"Racial differences in bicalutamide efficacy are overcome by using contemporary [ARAT agents] such as enzalutamide" in advanced prostate cancer, say the authors.
"ADT plus bicalutamide is inadequate therapy in all cases, but especially for Black patients," they note.
The lower response rate to bicalutamide among Black men "is very interesting and may indicate that there are biological factors at play that distinguish how patients of different races respond" to systemic therapy, said genitourinary oncologist Neeraj Agarwal, MD, professor of medicine at the University of Utah, Salt Lake City, Utah, and colleagues in an editorial.
The finding speaks to an issue of ongoing interest in prostate cancer: the role of biology vs socioeconomic factors in explaining the differences in outcomes between Black and White men, say the editorialists.
They explain that at the population level, the incidence and mortality of prostate cancer are higher among Black men. There is evidence that socioeconomic barriers lead to delayed diagnosis, unequal access to new therapeutics, and other problems. In metastatic prostate cancer, there also appear "to be differences in outcomes even when access to care is controlled, such as within a clinical trial patient population," suggesting biological influences, the researchers say.
On a level playing field, several investigations have reported better overall survival among Black men than White men in metastatic castration-resistant prostate cancer treated with contemporary options, including abiraterone, enzalutamide, sipuleucel-T, and docetaxel. Genetics might play a role, the editorialists comment.
Black Recruitment Is Key
Vaishampayan and her colleagues analyzed tumor samples to gain insight into race and response.
They found that high baseline ERG protein levels and changes in androgen metabolism enzymes and genetic resistance pathways might play a role in the difference in response to bicalutamide between their Black and non-Black patients, but they found nothing conclusive. They said that "further investigations exploring molecular biomarkers to help guide therapy are highly recommended."
"Ultimately," the editorialists write, "racial disparities in prostate cancer will be better understood with greater emphasis on enrollment of Black men in clinical trials across disease stages." The investigators "should be applauded" for prespecifying that at least 30% of the patients in the study would be Black, they comment.
"Increasing the enrollment of Black men in clinical trials requires increased focus from academic and industry leaders and input from community leaders and patient advocates to address the historical and societal barriers that prevent them from participation," the editorialists say.
Recruitment in the new study was cut short after a phase 3 trial found that survival was improved with abiraterone plus prednisone, a newer ARAT option. "We could no longer ethically randomize patients to bicalutamide," the investigators say.
This study was funded by Astellas, which markets enzalutamide in conjunction with Pfizer, and by the National Institutes of Health. Vaishampayan has received research funding from Astellas and consulting fees and honoraria from Pfizer, among other companies. Another investigator reported receiving advisory fees from both companies. Argawal is a paid Astellas and Pfizer consultant and is a Pfizer researcher. He also has ties to other companies.
M. Alexander Otto is a physician assistant with a master's degree in medical science. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape, including McClatchy and Bloomberg. He is an MIT Knight Science Journalism fellow. Email: firstname.lastname@example.org.
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Cite this: Prostate Cancer Drug Equally Effective in Black and White Men - Medscape - Jan 29, 2021.