medwireNews: The combination of bipolar androgen therapy (BAT) and nivolumab elicits responses and is well tolerated by men with metastatic castration-resistant prostate cancer (mCRPC), indicate phase 2 findings.
The researchers explained in a poster at the 2021 ASCO Annual Meeting that “anecdotal clinical responses to immune checkpoint blockade” have been observed in mCRPC patients previously treated with BAT, leading them to hypothesize that the combination “would be synergistic.”
The team therefore enrolled 45 men with asymptomatic disease who had received at least one prior novel androgen receptor-targeted therapy and no more than one line of chemotherapy in the open-label COMBAT-CRPC trial. Participants received BAT with intramuscular testosterone cypionate 400 mg every 4 weeks for a 12-week lead-in period, after which nivolumab 480 mg, also given every 4 weeks, was added for a further 12 weeks.
The median age of the participants was 69 years, the majority (86.7%) were White, and a third had previously been treated with at least two androgen receptor-targeted agents plus taxane chemotherapy.
The primary endpoint of a confirmed 50% or greater reduction in prostate-specific antigen levels (PSA50) was achieved by 40% of participants, which met the prespecified criteria of a 20% absolute increase from the 25% null hypothesis.
The objective response rate was 23.8% and the median radiographic progression-free survival was estimated at 5.7 months. A total of 11.1% of participants were free from radiographic progression for at least 11 months, and one patient had a complete radiographic response, which was ongoing at data analysis.
Mark Markowski (The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland, USA) and colleagues noted that most of the adverse events (AEs) were grade 1 or 2 in severity.
Edema and nausea/vomiting were the most frequent any-grade events attributable to treatment, each observed in 20% of patients, followed by back pain in 13% and diarrhea in 11%. There was one case each of grade 3 or worse edema, back pain, lipase elevation, fatigue, muscle pain, and pericarditis.
“BAT in combination with nivolumab is well tolerated,” with “durable responses” in some patients, summarized the researchers, adding that: “Biomarker analysis is ongoing to identify a molecular signature predictive of response.”
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