Largest Race-Based Survival Advantage to Date Seen in Men Receiving Sipuleucel-T for Prostate Cancer

A subanalysis of the PROCEED trial showed a surprisingly high survival advantage for African American men receiving immunotherapy for metastatic castration-resistant prostate cancer (mCRPC). The finding could lend insight into immune mechanisms that may favor African American men undergoing immunotherapy for prostate cancer, according to lead author Oliver Sartor, MD, medical director of Tulane Cancer Center and LaBorde professor of cancer research at Tulane Medical School.

The difference in overall survival was 9.5 months, which is the largest reported in mCRPC treatment. “Almost everybody who has seen the data thinks it’s a clinically significant difference. It’s also a real-world experience, with well over a hundred sites over the US, so it had a lot of geographic breadth to it,” Sartor told Cancer Network. He presented the analysis (abstract 5035) during a poster session at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting.

The study isn’t the first to indicate a survival advantage in African American men receiving sipuleucel-T. A pooled analysis of phase III trials showed a number needed to treat for an overall survival benefit of 3 in African American patients, compared to 8 overall.

The analysis of the PROCEED real-world registry examined the efficacy of the autologous cellular immunotherapy sipuleucel-T in 438 Caucasian and 219 African American PSA-matched mCRPC patients. Both groups received similar life-prolonging anticancer therapies after sipuleucel-T treatment.

The median follow-up was 46.6 months. The study included 1,649 Caucasians and 221 African Americans. African American patients had a longer overall survival (35.2 vs 29.9 months; hazard ratio [HR], 0.81; P = .03). After PSA matching (Caucasian patients, n = 438; African American patients, n = 219), the survival advantage remained in African Americans (35.3 vs 25.8 months; HR, 0.70; P < .001). In a multivariate analysis, African American race predicted overall survival after sipuleucel-T treatment (HR, 0.60; P < .001).

Sartor believes that the difference in survival has a biological explanation, but the mechanism remains unknown. Some evidence suggests that populations in Africa with prostate cancer have a higher mutational burden, and immunotherapy seems to be more effective in such tumors. There is also evidence that African American ancestry is associated with a more robust immune response. “Which one if either one (of those explanations) contributed to the survival advantage in this registry is not really clear,” said Sartor.

He plans to investigate tumor burden and other markers in African American patients to determine the source of the survival advantage. “We’re trying to get more prospective data on the pathophysiology, and then verify it with other immunotherapy agents. If this is an exploitable opportunity where African Americans can do better that’s pretty cool, because African Americans typically draw the short end of the stick when it comes to so many health-related issues,” said Sartor.

Not everyone was convinced by the findings. Asked to comment on the study, David Graham, MD, medical director at Levine Cancer Institute who also provides expert feedback to the American Society of Clinical Oncology, told Cancer Network, “I’m struggling in my own head whether this really represents a difference in the disease in African American men versus a signal of the improvements that we can see in the African American population when they have better access to care.”

“Is it something that leads us to possible future investigations (of biological differences in African Americans)? Absolutely. Is it something to highlight the fact that we need to make sure African Americans get the best care possible? Absolutely,” Graham said.