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Quality of Life in Men With Prostate Cancer Randomly Allocated to Receive Docetaxel or Abiraterone in the STAMPEDE Trial

  • Hannah L. Rush,
  • Laura Murphy,
  • Alicia K. Morgans,
  • Noel W. Clarke,
  • Adrian D. Cook,
  • Gerhardt Attard,
  • Archie Macnair,
  • David P. Dearnaley,
  • Christopher C. Parker,
  • J. Martin Russell,
  • Silke Gillessen,
  • David Matheson,
  • Robin Millman,
  • Christopher D. Brawley,
  • Cheryl Pugh,
  • Jacob S. Tanguay,
  • Robert J. Jones,
  • John Wagstaff,
  • Sarah Rudman,
  • Joe M. O'Sullivan,
  • Joanna Gale,
  • Alison Birtle,
  • Andrew Protheroe,
  • Emma Gray,
  • Carla Perna,
  • Shaun Tolan,
  • Neil McPhail,
  • Zaf I. Malik,
  • Salil Vengalil,
  • David Fackrell,
  • Peter Hoskin,
  • Matthew R. Sydes,
  • Simon Chowdhury,
  • Duncan C. Gilbert,
  • Mahesh K. B. Parmar,
  • Nicholas D. James,
  • Ruth E. Langley

Publication: Journal of Clinical Oncology, November 2021

Purpose

Docetaxel and abiraterone acetate plus prednisone or prednisolone (AAP) both improve survival when commenced alongside standard of care (SOC) androgen deprivation therapy in locally advanced or metastatic hormone-sensitive prostate cancer. Thus, patient-reported quality of life (QOL) data may guide treatment choices.

Methods

A group of patients within the STAMPEDE trial were contemporaneously enrolled with the possibility of being randomly allocated to receive either docetaxel + SOC or AAP + SOC. A mixed-model assessed QOL in those who had completed at least one QLQ-C30 + PR25 questionnaire. The primary outcome measure was difference in global-QOL (QLQ-C30 Q29&30) between patients allocated to docetaxel + SOC or AAP + SOC over the 2 years after random assignment, with a predefined criterion for clinically meaningful difference of > 4.0 points. Secondary outcome measures included longitudinal comparison of functional domains, pain, and fatigue, plus global-QOL at defined timepoints.

Results

Five hundred fifteen patients (173 docetaxel + SOC and 342 AAP + SOC) were included. Baseline characteristics, proportion of missing data, and mean baseline global-QOL scores (docetaxel + SOC 77.8 and AAP + SOC 78.0) were similar. Over the 2 years following random assignment, the mean modeled global-QOL score was +3.9 points (95% CI, +0.5 to +7.2; P = .022) higher in patients allocated to AAP + SOC. Global-QOL was higher for patients allocated to AAP + SOC over the first year (+5.7 points, 95% CI, +3.0 to +8.5; P < .001), particularly at 12 (+7.0 points, 95% CI, +3.0 to +11.0; P = .001) and 24 weeks (+8.3 points, 95% CI, +4.0 to +12.6; P < .001).

Conclusion

Patient-reported QOL was superior for patients allocated to receive AAP + SOC, compared with docetaxel + SOC over a 2-year period, narrowly missing the predefined value for clinical significance. Patients receiving AAP + SOC reported clinically meaningful higher global-QOL scores throughout the first year following random assignment.

by Dr. Roderick van den Bergh

The combination of hormonal treatment with upfront therapy is now the standard recommended treatment for metastasised prostate cancer.1,3 Different options for upfront treatment are available, including radiotherapy to the prostate, androgen-receptor-targeted agents, and docetaxel chemotherapy. Recently, the combination of abiraterone and docetaxel therapy has also been found to have an additional favourable impact. Therapy is currently chosen based on disease risk category and volume of the metastasis, but patient factors such as age and comorbidity are also important to consider when planning therapy.1,3 In clinical practice, financial factors are also sometimes decisive. Finally, the upfront therapy options all have a distinct pattern of side effects and impact on quality to life. This issue has been underexposed in the recent years.

Rush et al. present quality-of-life outcomes of men with locally advanced or metastatic hormone-sensitive prostate cancer (M+HSPC) included in the Stampede trial within the same period who were assigned to hormonal therapy plus docetaxel versus hormonal therapy plus abiraterone.2 Quality of life was measured over a 2-year period using the QLQ-C30 and PR25 questionnaires. The following questions were used as the main endpoints: “How would you rate your overall health during the last week?” and “How would you rate your overall quality of life during the last week?” Men randomised to receive hormonal therapy plus abiraterone were found to have a more favourable global quality-of-life score than men who received upfront docetaxel. This was particularly seen in the first year, during the 12–24-week period, after which the differences in QoL between the different therapies decreased, with little differences in the second year. The lower quality-of-life scores were likely caused by the toxicity of the chemotherapy. Also, short-term differences in fatigue, pain, physical functioning, social functioning, and role functioning were observed in favour of the abiraterone treatment arm.

This study provides important insights in a field where not much level-1 evidence is available. Data is derived from a randomised setting in the Stampede trial, which is the most important and high-quality trial in this area. PROMS play an increasingly important role in assessing the value of therapy for prostate cancer. The patient and physician perspective may be very different. A urologist or an oncologist may be focused on cancer-specific outcomes such as metastasis or survival. However, a patient may be more interested in side effects and the impact of the treatment options on the quality of life.

In M+HSPC, this may be especially relevant. An increasing number of combination therapies of hormonal therapy with chemotherapy, androgen-receptor-targeted agents, or radiation therapy have shown their efficacy in increasing overall survival. In an ideal situation, the different upfront treatment options are discussed with a patient, taking into account all the relevant outcomes: the benefit in survival, side effects, treatment duration, and impact on future treatment cycles. Although Rush et al. provide an invaluable insight in this decision process, uncertainties remain. The found differences exceeded the threshold for clinically meaningful differences, but these thresholds always remain prone to some subjectivity. Also, differences were only found during the first year. Patients starting on abiraterone are more likely to undergo chemotherapy in a subsequent treatment cycle. Hopefully, more quality-of-life data will emerge, further improving the treatment decision-making process for patients with high-risk or metastasised prostate cancer needing upfront therapy.

References:

  1. Mottet N, van den Bergh RCN, Briers E, et al. EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer-2020 Update. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur Urol. 2021 Feb;79(2):243-262.
  2. Rush HL, Murphy L, Morgans AK, et al. Quality of life in men with prostate cancer randomly allocated to receive docetaxel or abiraterone in the STAMPEDE trial. J Clin Oncol. 2021 Nov 10.
  3. Clarke NW, Ali A, Ingleby FC, et al. Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer: long-term survival results from the STAMPEDE trial. Ann Oncol. 2019 Dec 1;30(12):1992-2003.