Upfront chemo called ‘standard’ in hormone-naïve PCa

Docetaxel (Taxotere) added to standard hormone therapy significantly improved survival in men with newly diagnosed advanced prostate cancer who were hormone naïve, according to a study presented at the American Society of Clinical Oncology annual meeting in Chicago.   

Commentary: Upfront chemo? Yes, but...

Mean survival was extended by about 10 months among men who received docetaxel in the U.K. STAMPEDE (Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy) study, said lead investigator Nicholas David James, MD, PhD, of Queen Elizabeth Hospital Birmingham, U.K.

The addition of zoledronic acid (Zometa) to hormone therapy had no effect on survival, and adding zoledronic acid to docetaxel and hormone therapy was not more effective than adding docetaxel alone.

Dr. JamesDocetaxel up front should be considered for routine practice in men with newly diagnosed metastatic disease and in selected men with high-risk non-metastatic disease in view of substantial prolongation of failure-free survival, said Dr. James.

“For overall survival for docetaxel, the improvement is 25%... and that amounts to around a 10-month improvement in median survival,” Dr. James said. “It’s also clear that zoledronic acid does not benefit these patients and should not be offered as an upfront treatment for advanced prostate cancer.”

STAMPEDE enrolled more than 6,500 men starting long-term hormone therapy for the first time. Sixty-one percent had metastatic disease at entry and the remainder had high-risk, locally advanced non-metastatic prostate cancer (either node-positive or with two of three risk factors: stage T3/4, PSA ≥40.0 ng/mL, or Gleason sum score ≥8).

NEXT: Trial boasts unique multi-arm, multi-stage design

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The trial is unique in that it has a multi-arm, multi-stage design that can be modified to assess new therapies and to adapt to changes in the standard of care. The standard of care (SOC) in the continuously recruiting control arm changes with changes in treatment patterns. As the trial progresses, treatment arms that do not improve failure-free survival at interim analyses are terminated, and new arms are added to include emerging treatments.

Dr. James reported results on 2,962 hormone-naïve men (median age, 65 years) who were randomized to four of the study’s nine treatment arms, all of which passed the failure-free survival milestones: SOC, SOC with docetaxel for six cycles, SOC with zoledronic acid for 2 years, and SOC with both docetaxel and zoledronic acid. SOC was ≥3 years of androgen deprivation therapy, with local radiation for suitable patients. Only 6% of patients had prior local therapy.

Also see - Low-risk PCa: Higher radiation dose shows no benefit

After a median follow-up of 42 months, 948 men died. Median overall survival, the primary endpoint of the study, was an average of 10 months longer in the docetaxel arm compared to the SOC arm (77 vs. 67 months), with a relative improvement in survival of 24% (p=.003). For the subset of patients with metastatic disease, the average improvement in median overall survival was 22 months in the docetaxel arm (65 vs. 43 months), for a hazard ratio of 0.73 (p=.002). Docetaxel also extended failure-free survival (time to relapse) by 38% (p<.0000000001) in the overall cohort.

NEXT: Difference in overall survival was not significant between the SOC arm and the SOC plus zoledronic acid arm

The difference in overall survival was not significant between the SOC arm and the SOC plus zoledronic acid arm. Adding zoledronic acid to the combination of SOC and docetaxel did not improve outcomes compared with SOC with only docetaxel.

Seventy-six percent of patients randomized to docetaxel plus SOC and 69% randomized to docetaxel plus zoledronic acid and SOC received the full six cycles of treatment.

“This is the biggest trial of its kind and strongly suggests that adding chemotherapy to standard hormone therapy can extend the lives of men with advanced prostate cancer,” said ASCO Immediate Past President Peter Paul Yu, MD, of Palo Alto Medical Foundation in California. “Its innovative design is exciting, and one that we may begin to see in other areas of oncology.”

Grade 3 to 5 adverse events occurred at a frequency of 31% in the SOC arm, 31% in the SOC plus zoledronic acid arm, 51% in the SOC plus docetaxel arm, and 52% in the SOC plus zoledronic acid plus docetaxel arm. Toxicity in the docetaxel arms was driven by predictable chemotherapy side effects, including blood and lymphatic and blood/bone marrow adverse effects.

Use of “life-prolonging therapy” for disease progression was more common in the control and SOC plus zoledronic acid arms, with docetaxel being the most likely addition to therapy in these arms.

Dr. James has received honoraria and served as a consultant/adviser and on the speakers’ bureau for Sanofi and other pharmaceutical companies, and his institution has received research funding from Sanofi. Several of Dr. James’ co-authors have a financial or other relationship with Sanofi and/or other pharmaceutical companies.

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