ASCO GU 2020: Comparative Quality of Life in Patients Randomized Contemporaneously to Docetaxel or Abiraterone In the STAMPEDE Trial

San Francisco, CA USA (UroToday.com) In recent years, both docetaxel and abiraterone have been shown to improve overall survival when added to standard androgen deprivation therapy (ADT) for men with metastatic hormone-sensitive prostate cancer. These benefits have been shown in trials that individually compared docetaxel + ADT vs ADT alone (CHAARTED) and abiraterone + ADT vs ADT alone (LATITUDE), as well as in arms C (docetaxel) and G (abiraterone) of the multi-arm multi-stage trial STAMPEDE.

Arm C of STAMPEDE accrued between 2006 and 2013 and arm G accrued between 2011 and 2014. There was a period between November 15, 2011, and March 31, 2013, when both arms were accruing. This allows for a direct comparison of abiraterone + ADT with docetaxel + ADT in a cohort of patients that were randomized between the two therapies.

A comparison of these two groups demonstrated no difference in overall survival (Sydes et al), a finding which has been replicated in a separate meta-analysis (Wallis et al). Making the decision between which of these two therapies to begin in patient with newly diagnosed metastatic hormone-sensitive prostate cancer must then be governed by other considerations.

At Rapid Abstract Session A on Prostate Cancer at the 2020 Genitourinary Cancer Symposium, Dr. Hannah Rush presented a comparison of quality of life outcomes in patients enrolled to arms C and G of STAMPEDE during the period in which both arms were enrolling.

During this period, 173 men were randomized to arm C (docetaxel + ADT) and 341 were randomized to arm G (abiraterone + ADT). EORTC QLQ C30 and PR25 quality of life (QOL) questionnaires were completed at the time of enrollment and at 3, 6, 12 and 24 months. A difference in global quality of life score of >4 was considered clinically significant. The study was not powered specifically to detect differences in QOL in these populations.

Baseline characteristics and global quality of life score were similar between the two groups. The baseline mean and standard deviation in global QOL score were 77.8 and 20 in the docetaxel group and 78.0 and 19.3 in the abiraterone group respectively.

The primary outcome was average global QOL over the first two years of therapy. A statistically significant difference between the groups was detected favoring abiraterone (+3.9, 95%CI 0.6 to 7.1, p=0.021), but this was 0.1 points short of the pre-defined cutoff for clinical significance. Clinically and statistically significant differences were shown favoring abiraterone at both 3 and 6 months (+6.6, 95%CI 2.6 to 10.7, p=0.001; +8.0, 95% CI 3.6 to 12.3, p<0.001). Differences at 12 and 24 months were not clinically significant but still numerically favored abiraterone (+1.3, 95%CI -3.0 to 5.6, p=0.545; +4.5, 95%CI -0.25 to 9.2, p=0.063). Dr. Rush further highlighted that this pattern was very similar when looking specifically at the physical, role, and social functioning specifically as well as fatigue symptoms. Interestingly, pain symptoms started off similar in the two treatment groups and then diverged to favor abiraterone with longer follow up.

These results are interesting for several reasons. In STAMPEDE, docetaxel was administered 75mg/m2 3-weekly x6 cycles. Thus while it is not surprising that QOL would be superior in the abiraterone arm during that time as reflected in the 3 month time period, one might have expected the magnitude of this difference to be greater than the 6.6 points observed. On the other hand, one might have expected this difference to shift to favor docetaxel in the time when those patients had completed chemotherapy and the patients in the abiraterone arm were still taking abiraterone, however, this was not observed.

In choosing between abiraterone and docetaxel for men starting therapy for metastatic hormone-sensitive prostate cancer there remains no clear answer, however, these findings provide some evidence that in the absence of other factors favoring docetaxel, abiraterone may be favored.

Presented by: Hannah L. Rush, MBChB, Clinical Research Fellow, the University College London

Written by: Marshall Strother, MD, Society for Urologic Oncology Fellow, Division of Urologic Oncology, Fox Chase Cancer Center, Philadelphia PA @mcstroth at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California

References:

1. Wallis CJD, Klaassen Z, Bhindi B, et al. Comparison of Abiraterone Acetate and Docetaxel with Androgen Deprivation Therapy in High-risk and Metastatic Hormone-naïve Prostate Cancer: A Systematic Review and Network Meta-analysis. Eur Urol. 2018;73(6):834-844.

2. Sydes MR, Spears MR, Mason MD, et al. Adding abiraterone or docetaxel to long-term hormone therapy for prostate cancer: directly randomised data from the STAMPEDE multi-arm, multi-stage platform protocol. Ann Oncol. 2018;29(5):1235-1248.