The androgen-blocking medication Zytiga (abiraterone acetate) was associated with better quality of life than the chemotherapy drug docetaxel when used with standard treatment for advanced or high-risk prostate cancer, researchers reported at the American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium last week in San Francisco.
Differences in quality of life (QoL) scores were most evident during the first year of treatment—while chemotherapy was underway in the docetaxel group—though some benefit was still apparent at two years, according to presenter Hannah Rush, a clinical research fellow at University College London.
The long-running STAMPEDE trial (ClinicalTrials.gov number NCT00268476) is evaluating various treatment approaches for men starting hormone therapy for locally advanced or metastatic prostate cancer and those considered at high risk for disease progression.
The present analysis compared study participants who received either Zytiga or docetaxel in addition to standard-of-care treatment consisting of androgen deprivation therapy (ADT) with or without radiation.
Androgen deprivation therapy prevents the testicles from making testosterone and other male hormones, or androgens, that promote prostate cancer growth. But other organs, including the adrenal glands, can also make small amounts. Zytiga stops production of androgens throughout the body by blocking an enzyme required for their biosynthesis.
Previous analyses from the trial showed that both Zytiga and docetaxel delay disease progression and improve survival when added to standard-of-care therapy, so questions remain about which is a better option. Differences in quality of life and cost effectiveness could help guide treatment decisions.
Rush and her colleagues focused on quality of life among trial participants randomly assigned to receive standard therapy plus Zytiga (342 men) or standard therapy plus docetaxel (173 men). The median age was 66 years. Almost all were newly diagnosed, but about 5% were previously treated and experiencing a relapse. Zytiga was taken daily for the entire study period while docetaxel was administered in six three-week cycles.
The researchers used the European Organization for Research and Treatment of Cancer (EORTC) QOL Questionnaire, which includes a global, or overall, QoL score; separate domains for physical, role and social functioning; and symptoms including fatigue and pain. QoL scores range from 0 to 100, with higher score indicating better quality. A score difference of at least 4 points was considered to be clinically meaningful.
At the start of the study, global QoL scores were similar: 78.0 in the Zytiga group and 77.8 in the docetaxel group. However, the pain score was higher in the Zytiga group (56 versus 33, respectively).
After starting treatment, the global QoL score in the Zytiga group declined slowly and fairly steadily over two years. In the docetaxel group, the score initially dropped steeply, reaching its lowest level at around 18 to 24 weeks, after which it rose again through 48 weeks and then plateaued below the baseline level.
Over two years, the global score was 3.9 points higher in the Zytiga group, a difference that was statistically significant but fell just short of the clinical significance cutoff. Rush noted that the difference in QoL was clinically meaningful at three months and even more so at six months, but this was no longer the case at the one-year and two-year marks.
Similar patterns were seen when looking at the physical functioning, role functioning and social functioning domains. In all three domains, there was a slow decline in the Zytiga group, and a sharp decline followed by a rise and plateau in the docetaxel group. Over two years, the scores for all domains where significantly higher in the Zytiga group compared with the docetaxel group (differences of 4.5 points, 5.8 points and 5.0 points, respectively).
Not surprisingly, the steep drops in QoL in the docetaxel group occurred while chemotherapy was underway, with scores rising once treatment was finished at 18 months. However, these score remained below those of the Zytiga group even though the latter medication was taken continuously.
Looking at symptoms, fatigue scores rose after starting treatment in the Zytiga group, with the largest increase seen in the first year followed by a slower rise. In the docetaxel group, fatigue rose steeply for the first 24 weeks, then fell just as sharply through week 60 before roughly leveling off. Over two years, the fatigue score was 3.9 points higher in the Zytiga group.
Pain scores in the Zytiga group remained fairly stable during the first 24 weeks, then rose slowly for several months and dipped at 96 weeks. In the docetaxel group, pain scores fell during the first 12 weeks, then rose steeply through week 36 before roughly leveling off; the score dropped around week 72 but soon rose again. Over two years, the pain score was 6.3 points higher in the docetaxel group. In part, this may be attributable to peripheral neuropathy, or nerve damage, that can be a side effect of the chemotherapy.
“Patients on abiraterone have superior scores in key aspects of QoL,” the researchers concluded. “Differences [were] most marked in first year [but] smaller differences may persist to two years.”
Study coauthor Alicia Morgans, MD, of Northwestern University Feinberg School of Medicine told ASCO Daily News, “We are all hopeful that QoL, as reported from the patients themselves in this study, will be considered when men and their clinical teams face difficult treatment choices for metastatic hormone-sensitive prostate cancer.”
Click here to read the study abstract.
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