Major Finding: Prostate-specific antigen progression was observed at 6 months in 10% of the androgen suppression arm (ADT) vs. 1% of the ADT plus docetaxel arm (P = .002) of the trial.

Data Source: Phase III GETUG-AFU 15/0403 study in 385 men with hormone-naive metastatic prostate cancer.

Disclosures: The trial was supported by grants from the French Health Ministry, Sanofi-Aventis, AstraZeneca, and Amgen. Dr. Gravis and coauthors reported that they had no disclosures.

ORLANDO – The addition of docetaxel to androgen deprivation therapy significantly reduces PSA progression but is coupled with significant toxicity in hormone-naive metastatic prostate cancer, according to results of a phase III multicenter trial from France and Belgium.

Progression of prostate-specific antigen (PSA), defined as at least a 25% increase from baseline, was observed in 8% of the androgen suppression arm (ADT), versus 3% of the ADT plus docetaxel (Taxotere) arm at 3 months (P value = .08) and in 10% vs. 1%, respectively, after 6 months (P = .002), Dr. Gwenaelle Gravis reported at the symposium.

The addition of docetaxel also significantly increased the likelihood of a PSA response, defined as a decrease of at least 50% from baseline. A PSA response was achieved in 91% of the ADT plus docetaxel arm vs. 80% of the ADT arm at 3 months (P = .008) and in 95% vs. 86% when assessed at 6 months (P = .01), said Dr. Gravis of Institut Paoli-Calmettes, Marseille, France.

Although the data on the study's primary end point of overall survival are not yet available, these current findings are noteworthy in light of recent work by the Southwest Oncology Group demonstrating that PSA progression at 7 months is a strong predictor of death in patients who have metastatic hormone-sensitive and castration-resistant prostate cancer (J. Clin. Oncol. 2009;27:2450-6).

The French researchers randomized 192 patients to ADT plus docetaxel 75 mg/m

The patients were stratified according to prior systemic treatment and Glass risk group.

After the accrual of 215 patients, three toxic deaths occurred – two as a result of neutropenic fever and one from general impairment. This prompted the internal monitoring committee to recommend the use of granulocyte-colony stimulating factor from day 5 to day 10 after each docetaxel administration, with no subsequent deaths occurring, Dr. Gravis said.

Grades 3/4 hematologic toxicity in 188 evaluable ADT plus docetaxel patients include anemia (2%), neutropenia (32%), febrile neutropenia (7%) and septic death (1%), while only 1% anemia was reported in 185 evaluable ADT-only patients.

Other notable grade 3/4 toxicities occurring in the ADT plus docetaxel vs. ADT alone arms included fatigue (7% vs. 1%), erectile dysfunction (9% vs. 8%), decreased libido (6% vs. 5%) and hot flushes (4% vs. 2%).

“Docetaxel was associated with a significant increased, but manageable toxicity,” Dr. Gravis said at the symposium, which was cosponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology and the Society of Urologic Oncology.

Global quality of life scores were equivalent in both arms at 12 months in the GETUG-AFU 15/0403 study, sponsored by the National Federation of Comprehensive Cancer Centers with the collaboration of the French Association of Urology (AFU).

At baseline, the patients had a median age of 63 years and roughly half had a good performance status. The median PSA was 27 ng/mL, median Karnofsky score was 100 and 58% had a Gleason score of 8 or more.

Less than 30% received radical prostatectomy or radiotherapy and less than 10% received systemic treatment with chemotherapy or hormonal therapy. Most patients had up-front metastatic disease, with bone metastases present in 81% and nodes metastases in 55%, Dr. Gravis said.

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Questions of Survival Benefit Still Remain

This study supports the consideration of chemotherapy further up the treatment sequence, but there are Food and Drug Administration–approved alternatives such as Sipuleucel T, which has lower toxicity and need only be administered for three injections vs. nine cycles of docetaxel.

The survival benefit of androgen deprivation therapy and docetaxel in hormone-sensitive patients still needs to be demonstrated. Since PSA response was associated with survival benefit in the trials using docetaxel in the castration-resistant setting, it is reasonable to expect a survival benefit in those who are still hormone sensitive as well.

This still must be demonstrated, however, particularly if regulatory approval for this indication is sought. At the very least, this study provides some proof that the institution of chemotherapy can provide some benefit, even in patients who are hormone sensitive.

DR. BADRINATH R. KONETY is an ACS Fellow and chair of the department of urology, University of Minnesota, Minneapolis.

Docetaxel Slows PSA Progression in Prostate Ca