No Survival Benefit From Adding Docetaxel to ADT in Hormone-Sensitive Prostate Cancer

Gwenaelle Gravis, MD

Androgen deprivation therapy (ADT) with or without chemotherapy led to similar survival in men with advanced, metastatic hormone-sensitive prostate cancer, an updated analysis of a randomized trial showed.

After a median follow-up of almost 7 years, patients who received docetaxel in addition to ADT had a median overall survival (OS) of 60.9 months compared with 46.5 months for men who received ADT alone, a 14 month difference. A subgroup analysis limited to men with high-volume disease also failed to show a significant difference between treatment groups, as reported at the February 2015 Genitourinary Cancers Symposium in Orlando.

“We observed no significant difference in overall survival in the total population or in the retrospective analysis of patients with high-volume disease,” said Gwenaelle Gravis, MD, a medical oncologist at the Paoli-Calmettes Institute in Marseille, France. “The group of men with high-volume disease was a statistically underpowered subset.”

The findings contrast with those from the larger National Cancer Institute (NCI)-sponsored E3805 study reported last year at the 2014 American Society of Clinical Oncology annual meeting. That randomized trial showed a clinically and statistically significant 13.6-month difference in overall survival in favor of patients who received docetaxel in addition to ADT.

The US-based trial enrolled men with high-volume disease, which might explain the disparity with the French study. However, Gravis pointed out that in the European study the subgroup of analysis of men with high-volume disease showed they had similar outcomes with or without docetaxel.

The findings presented at the GU symposium came from an update of the randomized phase III GETUG-AFU 15 trial. The newer study involved 385 men with mCRPC and no prior hormonal therapy. Patients enrolled at 29 centers in France and one in Belgium underwent surgical or chemical ADT and were randomized to docetaxel 75 mg every 3 weeks for a maximum of 9 cycles of treatment. The primary end point was OS.

The primary results, reported after a median follow-up of 50 months, showed a median OS of 58.9 months in the docetaxel arm and 54.2 months among men treated with ADT alone (Lancet Oncol. 2013;14:149-158).

Following presentation of results from the NCI-sponsored E3805 trial, investigators in the GETUG-AFU 15 trial performed another survival analysis to determine whether chemotherapy added to ADT provided a survival benefit with longer follow-up.

The 14-month survival difference in the updated French analysis still did not achieve statistical significance (P =.44). The docetaxel group did have significantly better biological progression-free survival (PFS), (mean of 22.9 months versus 12.9 months for ADT alone, P =.0021).

The analysis of men with high-volume disease comprised 183 study participants. Gravis and colleagues used the NCI-sponsored study’s definition of high volume: lung or liver metastases and/or 4 or more bone metastases, at least 1 of which was beyond the pelvis and the vertebral column.

Median OS was 35.1 months with ADT alone and 39 months with ADT plus docetaxel, a nonsignificant difference. Biological PFS did differ significantly in favor of docetaxel (15.2 versus 9.2 months, P =.0039).

Median OS in the low-volume subgroup was 83.1 months with docetaxel but had yet to be reached in the men randomized to ADT alone. Biological PFS favored ADT plus docetaxel, but the difference did not achieve statistical significance (40.9 versus 22 months, P =.0533).

Yet another randomized trial comparing ADT alone or with chemotherapy is ongoing. Gravis suggested that results of the trial—specifically, a pooled analysis of all three trials—might help resolve the uncertainty created by the disparate results of her trial and those from the NCI-sponsored study and allow clinicians to individualize therapy to ensure that each patient receives the most appropriate treatment.

In the absence of a definitive explanation for the different outcomes, Gravis speculated that men with high-volume disease in the E3805 trial might have started docetaxel earlier, as compared with men in the European trial.

Gravis G, Boher JM, Joly F, et al. Androgen deprivation therapy (ADT) plus docetaxel (D) versus ADT alone for hormone-naïve metastatic prostate cancer (PCa): Long-term analysis of the GETUG-AFU 15 phase III trial. Presented at: 2015 Genitourinary Cancers Symposium; February 26-28, 2015; Orlando, FL. Abstract 140.

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