First-line abiraterone benefit differs by race in prostate cancer subset
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First-line abiraterone acetate for metastatic castration-resistant prostate cancer conferred longer OS among Black men compared with non-Hispanic white men, according to study results published in JAMA Network Open.
“This difference in outcomes may be driven by decreased benefit of abiraterone, relative to other therapies like enzalutamide, among non-Hispanic white men,” Mallika Marar, MD, MBA, resident physician in radiation oncology at Stanford University, told Healio. “This finding was surprising and future investigation should move beyond studying race itself and consider factors such as differences in expression of genetic variants as a potential mediator of abiraterone outcomes.”
Background and methodology
Marar and colleagues pursued the research because Black men are both underrepresented in seminal phase 3 trials in metastatic castration-resistant prostate cancer and are more prone to develop and die of the disease than white men.
“Recent evidence, including prospective data from the Abi-Race trial, suggests improved metastatic prostate cancer outcomes for African American men treated with abiraterone as compared with non-Hispanic White men. However, the reasons underlying these suggested differences in abiraterone efficacy, relative to other therapies like enzalutamide, remain unexplored,” Marar told Healio. “We were interested in investigating whether this effect was borne out in a real-world cohort of men receiving first-line treatment for metastatic prostate cancer in a predominantly community-based practice setting.”
The analysis included 3,808 men (68.7% non-Hispanic white, mean age at diagnosis, 74 years vs. 10.6% Black, mean age at diagnosis, 69 years) in the Flatiron Health database with newly diagnosed metastatic castration-resistant prostate cancer who received first-line systemic therapy between 2012, and 2018. Of them, 1,729 (45.4%) received first-line abiraterone acetate (Zytiga, Janssen).
OS from the start of first-line treatment served as the primary endpoint; investigators stratified OS within each group, with first-line enzalutamide (Xtandi, Astellas/Pfizer) as the comparator.
Median follow-up was 13 months (interquartile range [IQR], 7-22 months).
Key findings
Results among those who received first-line abiraterone acetate showed longer median OS for Black men (23 months; IQR, 10-37 months) than non-Hispanic white men (17 months; IQR, 9-32 months). Researchers calculated an inverse probability of treatment weighting HR of 0.76 (95% CI, 0.6-0.98).
Further analysis revealed a race-by-treatment interaction for first-line abiraterone acetate vs. first-line enzalutamide (HR among non-Hispanic white men = 1.21; 95% CI, 1.06-1.38; HR among Black men = 1.05; 95% CI, 0.74-1.5).
OS did not differ with either treatment among Black men (median, 24 months). However, first-line abiraterone acetate conferred shorter median OS among non-Hispanic white men (17 months; IQR, 9-32 months) than first-line enzalutamide (20 months; IQR, 10-36 months) with an inverse probability of treatment weighting HR of 1.21 (95% CI, 1.06-1.38).
Conclusions
Marar and colleagues called for future research examining the drivers of differential outcomes between metastatic castration-resistant prostate cancer agents, including differences in genetic factors and socioeconomic status, to inform treatment strategies. Investigators should continue to aim for increased numbers of Black men and other underrepresented populations in further studies, they wrote.
“One important factor being explored is the expression of genetic variants that may impact treatment response,” Marar said. “This, in turn, could inform precision oncology therapeutic strategies in prostate cancer.”
For more information:
Mallika Marar, MD, MBA, can be reached at Department of Radiation Oncology, Stanford Cancer Center Palo Alto, 875 Blake Wilbur Drive, Stanford, CA 94305-5847; email: mararm@stanford.edu.
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