Patients with locally advanced or metastatic hormone-sensitive prostate cancer who received docetaxel and abiraterone acetate plus prednisone or prednisolone and standard of care androgen deprivation therapy had superior patient-reported quality of life compared with patients who received docetaxel plus ADT, although the improvement narrowly missed the predefined value for clinical significance.
Patients with locally advanced or metastatic hormone-sensitive prostate cancer (mHSPC) who received docetaxel and abiraterone acetate (Zytiga) plus prednisone or prednisolone (AAP) and standard of care (SOC) androgen deprivation therapy (ADT) had superior patient-reported quality of life (QOL) compared with patients who received docetaxel plus ADT, although the improvement narrowly missed the predefined value for clinical significance, according to findings from a substudy of the ongoing phase 2/3 STAMPEDE trial (NCT00268476) that were published in the Journal of Clinical Oncology.1
Over a 2-year period, the mean modeled global QOL score was 3.9 points higher in patients who received AAP plus SOC (74.5; SE 1.0) vs docetaxel plus SOC (70.6; SE, 1.4; 95% CI, 0.5-7.2; P = .022). This was considered statistically significant; however, the metric failed to reach the predefined threshold of at least 4 points denoting a clinically meaningful difference. Over a 1-year period, global-QOL was 5.7 points higher (95% CI, 3-8.5; P < .001).
Moreover, at 1-year, the global QOL was particularly high at 12 (+7.0 points with AAP/SOC, 95% CI, 3-11.0; P = .001) and 24 weeks (+8.3 points with AAP/SOC, 95% CI, 4.0-12.6; P < .001).
The STAMPEDE trial is a multi-arm, multistage platform trial that is evaluating several therapeutic regimens given with or instead of long-term ADT in men with advancing or metastatic prostate cancer. Findings from the study, as well as other studies, have demonstrated that combining docetaxel or abiraterone plus prednisone or prednisolone with concurrent ADT prolongs overall survival vs ADT alone in this patient population.
“Patients with prostate cancer report a willingness to compromise maximal survival to achieve better QOL. Although ADT is associated with multiple [adverse] effects that negatively affect QOL, the impact on QOL from additional treatment with docetaxel or AAP has not been directly compared,” wrote the study authors.
Within the STAMPEDE trial, a group of patients were contemporaneously enrolled with the potential to be randomized to receive 6 cycles of docetaxel with daily prednisolone during chemotherapy plus SOC or daily AAP plus SOC.
Overall, 1348 patients were randomly assigned to the STAMPEDE trial; 377 patients received AAP plus SOC, and 189 patients received docetaxel plus SOC. The remaining patients were randomized to other arms of the study. Of all patients in the first 2 mentioned arms, 515 completed at least 1 QOL questionnaire; 342 patients received AAP plus SOC and 173 patients received docetaxel plus SOC.
The QOL assessments utilized included the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 version 3.0 questionnaire with the prostate-specific module PR25, which was completed at baseline, every 6 weeks for the first 6 months, every 12 weeks for 2 years, every 6 months for 5 years, and annually thereafter.
The primary outcome measure of the substudy was the difference in global QOL scores over the first 2 years following randomization to AAP plus SOC or docetaxel plus SOC. Secondary outcome measures included the difference over 2 years in each functional domain (physical, emotional, role, cognitive, and social) and symptoms (pain and fatigue). Exploratory analyses included the difference in global QOL over the first year following randomization, the difference in patients with metastatic vs nonmetastatic disease, and post-progression.
Baseline characteristics of the patients included in the substudy were similar between groups, including pain at baseline and validated prognostic variables like age, stage, and World Health Organization performance status. Additionally, baseline global QOL scores were similar at 78 (standard deviation [SD], 19.3) with AAP plus SOC vs 77.8 (SD, 20) for docetaxel plus SOC.
Baseline questionnaires were received from 89% of patients overall.
Additionally, 20.8% of patients who received AAP plus SOC vs 19.9% of patients who received docetaxel plus SOC were censored for starting second-line treatment or death.
Additional results showed the failure-free survival rate, defined as the time from random assignment to the first of biochemical, lymph node, or distant metastatic progression, or prostate cancer–specific death, was 76.4% with AAP plus SOC vs 64.1% with docetaxel plus SOC. Moreover, 41 vs 25 patients, respectively, were given subsequent treatment with life-prolonging therapy.
In the AAP/SOC arm, nearly all patients (99%) started AAP and the median time on treatment was 697 days (interquartile range, 332-751). At the last QOL questionnaire within the first 2 years, 77% of patients remained on AAP and 11 patients discontinued treatment because of toxicity.
QLQ-C30 scores demonstrated a statistically significant and clinically meaningful difference favoring AAP plus SOC in the functional domain of social function (+5; 95% CI, 1.3-8.7; P = .008). Statistically significant but not clinically meaningful differences favoring AAP plus SOC were reported regarding physical (+4.5, 95% CI, 1.3-7.7; P = .006) and role function (+5.8, 95% CI, 1.6-9.9; P = .006). No difference in cognitive or emotion function was observed.
Fatigue (-3.9; 95% CI, -7.7- -0.1; P = .042) and pain (-6.3; 95% CI, -10- -2.6; P < .001) scores also favored the AAP plus SOC arm; however, the difference in fatigue score was not clinically meaningful.
Evidence emerged of higher global QOL scores among patients with metastatic disease who received AAP plus SOC vs docetaxel plus SOC (+4.5; 95% CI, 0.3-8.6; P = .036). The same was not found for patients with nonmetastatic disease (+3.0; 95% CI, -2.4-8.3; P = .275). Ultimately, findings from an interaction test did not demonstrate a differential effect on difference between QOL scores between regimens (interaction P = .701).
Over 2 years following randomization, the average QLQ-C30 summary score was 85 (SE, 0.7) with AAP plus SOC vs 82.4 (standard error [SE], 1) with docetaxel plus SOC, which comprised a 2.6-point difference (95% CI, 0.1-5.1; P = .041).
No evidence of difference in global QOL scores following progression was observed among evaluable patients (-4.9; 95% CI, -13.2-3.4; P = .247).
Finally, no difference between global QOL scores was observed in patients who received docetaxel plus SOC vs those who received docetaxel alone (-1.0; 95% CI, -4.4-2.3; P = .553). Moreover, higher though not clinically meaningful scores were observed in patients who received AAP plus SOC vs docetaxel alone (+2.9; 95% CI, 0.1-5.6; P = .040).
“We believe the longitudinal analyses and associated figures illustrate these data clearly for patients and clinicians. This greater understanding of difference in QOL between these treatments will inform decisions about which up-front treatment to use alongside ADT,” the study authors concluded.