Mitoxantrone plus prednisone (MP) added to androgen deprivation therapy (ADT) does not improve outcomes in patients with clinically localized prostate cancer, according to the results of a large long-term multicenter clinical trial.

At a follow-up time of almost 11 years, outcomes were nearly the same whether patients had received chemotherapy and ADT or just ADT.

Overall survival was 87% in the cohort that received ADT only and 86% in the study arm that received ADT plus MP (HR 1.05 (CI 0.78, 1.42), P = .74). Recurrence-free survival was 84% in both groups (HR 0.98 (CI 0.78, 1.23), P = .83).

Disease free survival was 72% in both arms, and there was no statistical difference. Similarly, death without recurrence were also similar in both arms.

“Survival was greater than anticipated in both arms,” lead author L. Michael Glode, MD, of the University of Colorado, Denver, said in a press briefing held at the 2017 genitourinary cancers symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology. “There is no evidence that MP improves prostate cancer specific survival when added to 2 years of adjuvant ADT.”

There were 85 deaths in the ADT arm compared to 91 in the chemotherapy arm. Prostate cancer accounted for 18% of deaths among the patients receiving ADT only and 22% in the chemotherapy arm, but the incidence of other cancers was twice as common in the chemotherapy arm as in the ADT only arm.

“The predominant cancers were GI and lung,” said Dr. Glode, “And noncancer deaths were variable.”

Of note, MP increased the incidence of leukemia (one case in the ADT group vs. five in the chemotherapy group).

“This trial demonstrates the feasibility of doing adjuvant trials in prostate cancer post radical prostatectomy,” said Dr. Glode. “Survival was greater than anticipated in both arms.”

The assumptions of this trial were that 2 years of adjuvant ADT would improve overall survival and progression-free survival although definitive data were unavailable.

The rationale for doing a study using adjuvant therapy was based on published literature, in which findings had showed that while short-term neoadjuvant ADT prior to prostatectomy reduced positive margins, it had no effect on disease-free survival. In addition, research had shown that longer-term ADT improved outcomes for patients undergoing curative radiation therapy.

For chemotherapy, Dr. Glode pointed to data showing that adjuvant chemotherapy improved progression-free survival in patients who had undergone both prostatectomy and radiation therapy.

“We hypothesized that the addition of modestly active chemotherapy earlier in disease might improve overall survival and progression-free survival,” he said.

The primary objective was overall survival and the secondary endpoint was disease-free survival.

The S9921 trial enrolled 983 patients from October 1999 to January 2007 with clinically localized prostate cancer, before enrollment ceased because of the increased incidence of leukemia in the ADT plus MP arm.

Of this group, 22 patients were ineligible, and the remaining patients were assigned to goserelin acetate 10.8 mg plus bicalutamide 50 mg (n = 481) or the same ADT plus MP (n = 480).

The patients were stratified by stage (≤pT2, ≥pT3, N0 or N+), Gleason score, and intent to receive adjuvant radiation, and the presurgical PSA was 7.6 ng/mL. Radiation therapy was allowed in both arms at physician discretion, and 26% intended to receive radiation therapy.

In the ADT only arm, 402 completed the treatment, and 390 completed treatment in the ADT plus chemotherapy arm.

Grade 3 or higher adverse events were more common in the chemotherapy group (56%/30%, P less than .0001). “As for toxicities, the main difference was the presence of leukopenia in the chemotherapy arm,” said Dr. Glode.

The study was funded by Southwest Oncology Group’s Urologic Cancer Outreach Program, Eastern Cooperative Oncology Group, Cancer and Leukemia Group B, Clinical Trials Support Unit, and National Cancer Institute. None of the authors had disclosures.