Dose-reduced ARPI leads to inferior survival in CRPC patients

Reduced-dose treatment with androgen receptor pathway inhibitors (ARPI) lead to poorer oncological outcomes relative to full-dose regimens in castration-resistant prostate cancer (CRPC), a recent study has found.

A total of 162 CRPC patients (median age 75 years) treated with ARPI participated in the study. Thirty-three (20.4 percent) saw dose reductions during ARPI, and progression-free (PFS) and overall (OS) survival estimates were compared against patients who continued to receive full-dose ARPI.

Over a median follow-up of 35.0 months, 133 patients (82.1 percent) experienced disease progression, defined as an increase in prostate specific antigen (PSA) of >2 ng/mL, a 50-percent increase over the nadir, or radiographic progression. Meanwhile, 97 patients died, yielding an all-cause mortality rate of 59.9 percent.

The resulting median PFS and OS were 8.7 months and 32.9 months, respectively. Stratifying according to ARPI dose showed that PFS was shorter in those who received dose reductions (6.6 vs 9.6 months; p=0.072). Such an effect was strongest in those who saw 75-percent dose reductions, in whom the median PFS was only 2.7 months.

A similar pattern was reported for OS. Median OS was 34.5 months in the standard-dose group as opposed to only 16.7 months in dose-reduced patients. In those who saw ARPI reductions of 75 percent, median OS was 6.3 months.

Multivariate analysis confirmed that dose reduction was a significant correlate of PFS (hazard ratio [HR], 1.64, 95 percent confidence interval [CI], 1,03–2.59; p=0.036), but not OS (HR, 1.52, 95 percent CI, 0.90–2.59; p=0.12).