SAN FRANCISCO – Adding docetaxel to first-line long-term hormone therapy for advanced prostate cancer, whether metastatic or not, improves quality of life, reduces need for subsequent therapy, and is cost effective, suggests a new analysis of data from the STAMPEDE trial.

Hormone therapy alone has historically been standard of care for this disease, lead study author Nicholas D. James, MD, PhD, a professor of clinical oncology at the University of Birmingham, England, noted in a press briefing in advance of the 2018 Genitourinary Cancers Symposium.

But evidence shows that adding docetaxel (Taxotere) improves failure-free survival by 40% and overall survival by 25% in metastatic disease, and failure-free survival by 40% in high-risk nonmetastatic disease, with a trend toward overall survival benefit. Furthermore, adding docetaxel reduces symptomatic skeletal events by about 40% in both disease settings.

The new analysis focused on health economic and quality of life outcomes. Results of a model based largely on STAMPEDE data showed that adding docetaxel to first-line hormone therapy yielded an increase of about 0.4 quality-adjusted life-years among men with nonmetastatic disease and about 0.5 quality-adjusted life-years among men with metastatic disease.

Adding docetaxel actually led to a small reduction in total lifetime costs, on the order of several hundred pounds sterling, for patients with nonmetastatic disease, because the drug costs were more than offset by reductions in costs associated with adverse outcomes. On the other hand, adding docetaxel increased total costs by a fairly modest amount, roughly 3,000 pounds sterling, for patients with metastatic disease, but that increase was due in large part to costs associated with prolonged survival.

“Upfront docetaxel gives you a gain in quality-adjusted life-years in all subgroups,” Dr. James said. “Analysis suggests a high degree of certainty relating to the quality-adjusted life-year gain associated with docetaxel.”

“The results therefore support the existing health care policy in the U.K. and elsewhere across the world in newly diagnosed metastatic patients. You’ve got a pretty modest cost for a survival gain and a quality gain,” he maintained. “But very importantly, we think these results extend the applicability to nonmetastatic patients because at the patient level there is very clear evidence of a quality-adjusted life-year gain, and the modeling also predicts an eventual survival gain. And at the provider level, it’s a very cost-effective use of resources. For a very modest upfront docetaxel cost, it actually is cost saving in the nonmetastatic patient because of the subsequent downstream [averted events], things like spinal cord compression.”

Full results of the analysis, including model-predicted overall survival, will be reported at the symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.

Clinical implications

“In this analysis of data from the STAMPEDE trial, we see that docetaxel, a chemotherapy drug that has been in our armamentarium for prostate cancer for over a decade, may be applied in earlier and earlier settings in the disease,” commented ASCO expert and moderator of the press briefing, Sumanta K. Pal, MD. “Dr. James has previously reported the survival gains associated with this drug, but today adds the dimension of demonstrating improved quality of life and potentially cost-effectiveness as well.”

Results can be compared against those seen with abiraterone (Zytiga), an oral hormonal therapy that has shown similar benefit in these same patient populations, he said. “Abiraterone may offer the benefit of improved tolerability over a short course versus chemotherapy, but does require a much more extensive duration of use and further mandates concomitant use of prednisone.”

“Understanding the cost and quality of life associated with abiraterone in this setting may help adjudicate between giving this drug or docetaxel for the patients that Dr. James describes,” concluded Dr. Pal, codirector of the Kidney Cancer Program at City of Hope, Duarte, Calif.

Study details

The ongoing multi-arm STAMPEDE randomized trial has thus far enrolled more than 9,000 men with advanced (nonmetastatic and metastatic) prostate cancer and evaluated 10 treatments for the disease. About 60% of enrolled men have metastases.

Dr. James and colleagues developed a state transition model to reflect the natural history of patients entering the trial. Rate of progression and quality of life data (assessed with the EuroQol EQ-5D tool) were ascertained from the trial; costs came from both the trial and the literature.

Results indicated that, despite the adverse quality of life impacts of receiving chemotherapy and of living longer with metastatic disease, adding docetaxel to hormone therapy ultimately increased quality-adjusted life-years, with similar benefit seen in both nonmetastatic and metastatic disease.

“It was very interesting to us that, in the nonmetastatic patients, the quality-adjusted life-year gain was almost of the same magnitude, despite there being no evidence yet in STAMPEDE follow-up of a definite survival benefit in this group,” Dr. James noted. In these patients, chemotherapy has an upfront “quality of life penalty,” but that is offset by the later quality of life gains from delaying relapses (and thus time to further treatment) and, when nonmetastatic disease becomes metastatic, reducing events such as fractures and spinal cord compression.

“These later gains essentially wipe out the quality of life cost, if you like, from docetaxel, giving you a net gain almost as big in magnitude as the gain in metastatic patients,” he summarized. “We think this is a really important new finding.”

In a cost breakdown, adding docetaxel to hormone therapy increased drug costs in patients with both nonmetastatic and metastatic disease. Costs for end of life care, adverse events, and monitoring changed little in either group

Adding docetaxel increased costs for management by about 1,000 pounds sterling in patients with nonmetastatic disease (likely related to the chemotherapy administration) and about 2,000 pounds sterling in patients with metastatic disease (likely related to chemotherapy administration and longer survival).

Of special note, with addition of docetaxel, costs for other life-prolonging therapies – abiraterone, enzalutamide (Xtandi), radium (Xofigo), and similar treatments – fell by about 2,500 pounds sterling in nonmetastatic disease and 1,000 pounds sterling in metastatic disease. These savings are attributable to a shorter period of time spent in the relapsed state for patients who receive docetaxel, Dr. James explained. And savings are much greater for patients with nonmetastatic disease because they spend a much shorter time post relapse, given that the extended failure-free survival with docetaxel does not fully translate to extended overall survival.

When it comes to total lifetime costs, “basically, your downstream savings almost completely wipe out, even in the metastatic patients, the upfront costs,” he summarized.

Dr. James disclosed that he receives honoraria from Sanofi/Aventis, Janssen, Astellas Medivation, Bayer Health, and Merck Sharp & Dohme; has a consulting or advisory role with Janssen, Sanofi/Aventis, Merck Sharp & Dohme, Roche, Astellas Medivation, and Bayer; and is on the speakers’ bureau for Bayer, Janssen, Roche, and Ipsen; in addition, his institution receives research funding from Janssen, Astellas Medivation, Bayer, Sanofi/Aventis, and Roche. The study was funded by Cancer Research UK and the Medical Research Council, United Kingdom.

op@frontlinemedcom.com

SOURCE: James ND et al. GUCS Abstract 162.

Adding docetaxel to hormone therapy for advanced prostate cancer nets QOL benefit