Health-related QOL is comparable among ARPI regimens for CSPC

A secondary analysis of the phase 2 LACOG0415 trial (NCT02867020) showed no statistically significant difference in health-related quality of life (HRQOL) between treatment with androgen deprivation therapy (ADT) plus abiraterone acetate (Zytiga) and prednisone (AAP) compared with apalutamide (Erleada, APA) alone or APA plus AAP in patients with advanced castration-sensitive prostate cancer (CSPC).¹

Patients in the APA cohort demonstrated more favorable outcomes in the time to deterioration of the emotional well-being score.

The findings were published in JAMA Network Open.

Previously reported findings from the noncomparative LACOG0415 trial showed that the ADT-free alternative regimens led to high prostate-specific antigen (PSA) responses in patients with advanced CSPC, though the APA arm did not achieve the primary end point of a PSA level of 0.2 ng/mL or lower at week 25.²Specifically, a PSA level of 0.2 ng/mL or lower was achieved in 75.6% of patients in the ADT plus AAP arm, 60% of patients in the APA alone arm, and 79.5% of patients in the APA plus AAP arm.Two-year overall survival was not statistically different between the treatment arms (P = .59).

Regarding safety, grade 3-4 adverse events were observed in 31% of patients in the ADT plus AAP arm, 21.4% of patients in the APA arm, and 36.4% of patients in the APA plus AAP arm. No new safety signals were reported.

In total, the study included 128 patients with advanced CSPC who were randomly assigned 1:1:1 to receive ADT plus AAP (n = 42), APA alone (n = 42), or APA plus AAP (n = 44).

The current study assessed HRQOL outcomes in these patients via the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire and its subscores (emotional well-being, functional well-being, and prostate cancer subscale). Scores on the questionnaire range from 0 to 156, with higher scores indicating better HRQOL. Participants in the study completed the questionnaires every 4 weeks for up to 25 weeks.

Among the 128 patients in the study, 95.3% (n = 122) completed the FACT-P questionnaire at baseline, and 79.7% (n = 102) completed the questionnaire at week 25.

FACT-P total scores and subscores were similar between all arms at baseline.

At 25 weeks, FACT-P total score remained comparable between the arms, with a mean score of 122.3 (SD, 20.4) in the ADT plus AAP arm, 119.5 (SD, 16.4) in the APA alone arm, and 119.9 (SD, 20.3) in the AAP plus APA arm. Data also showed no statistically significant difference between the arms across FACT-P subscores.

The investigators also found no significant difference between the 3 arms in the time to FACT-P total score deterioration. This was consistent across all subscores except for the time to deterioration of the emotional well-being score, for which patients in the APA cohort demonstrated more favorable outcomes vs those in the ADT plus AAP arm (reference arm: ADT plus AAP arm; APA alone: HR, 0.37; 95% CI, 0.15-0.85; P = .02; AAP plus APA: HR, 0.56; 95% CI, 0.26-1.19; P = .13).

According to the authors, “The low rate of adverse events, the high PSA decrease rate, and the short follow-up of the HRQOL questionnaires may explain the stability during the trial and the absence of differences among arms.”

Thus, the authors suggest that larger studies with longer-term follow-up and more specific questionnaires are warranted to accurately assess outcomes of ADT-free alternatives. Specifically, they note that assessments should account for individual changes in patient’s lives and other symptoms not captured in the FACT-P questionnaire.

Overall, they concluded, “In this secondary analysis of a randomized clinical trial, HRQOL remained stable during treatment with ADT plus AAP, APA alone, and AAP plus APA for patients with advanced CSPC…The difference detected in time to deterioration of the [emotional well-being] score between APA alone and ADT plus AAP should be assessed in future research. Larger studies with longer follow-up and more specific questionnaires are needed to further evaluate HRQOL with these treatment strategies.”

References

1. Bastos DA, Soares A, Schutz FAB, et al. Androgen receptor pathway inhibitor therapy for advanced prostate cancer: Secondary analysis of a randomized clinical trial. JAMA Netw Open. 2025;8(1):e2454253.doi:10.1001/jamanetworkopen.2024.54253

2. Maluf FC, Schutz FA, Cronemberger EH, et al. A phase 2 randomized clinical trial of abiraterone plus ADT, apalutamide, or abiraterone and apalutamide in patients with advanced prostate cancer with non-castrate testosterone levels (LACOG 0415). Eur J Cancer. 2021:158:63-71.doi:10.1016/j.ejca.2021.08.032