No Survival Benefit Reported With Docetaxel Added to Hormone Therapy in Metastatic Prostate Cancer


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Gwenaelle Gravis, MD

Updated Analysis of the GETUG-AFU 15 Trial

In a retrospective analysis, no improvement [in overall survival] was observed in patients with low-volume disease with the addition of docetaxel.

—Gwenaelle Gravis, MD

Docetaxel added to androgen-deprivation therapy did not improve overall survival over androgen-deprivation therapy alone in hormone-naive metastatic prostate cancer, according to an updated analysis of the GETUG-AFU 15 trial presented at the 2015 Genitourinary Cancers Symposium.1 In a retrospective analysis component of the trial, docetaxel provided an additional 14 months of survival overall and a 4-month difference in patients with high-volume disease, but neither was statistically significant.

“We wanted to see whether docetaxel in an earlier setting could improve survival in metastatic cancer,” said presenting author Gwenaelle Gravis, MD, of the Institut Paoli-Calmettes, Marseille, France.

Study Details

GETUG-AFU 15 enrolled 385 patients between October 2004 and December 2008 and randomized them to receive either androgen-deprivation therapy plus docetaxel or androgen-deprivation therapy alone (luteinizing hormone-releasing hormone agonist or maximum androgen blockade or bilateral orchiectomy). The study was conducted at 30 centers (29 in France and 1 in Belgium).

The patients’ median age was 63 years. Fifty-eight percent had a Gleason score of ≥ 8. Most cases were metastatic at diagnosis: 76% in the docetaxel arm and 67% in the androgen-deprivation therapy alone arm. The median follow-up was 50 months.

In the original analysis, with a median follow-up of 50 months, the time to disease progression was prolonged in the docetaxel arm, but median survival was not significantly different, Dr. Gravis noted. In the updated analysis, with a median follow-up of 80+ months, median overall survival was 46.5 months (range = 39.1–60.6 months) for androgen-deprivation therapy alone vs 60.9 months (range = 46.1–71.4 months; hazard ratio = 0.9 (0.7–1.2) for androgen-deprivation therapy plus docetaxel.

Results Differ From the CHAARTED Study

These results differed from those of the E2805 CHAARTED study presented by Christopher Sweeney, MD, at the 2014 ASCO Annual Meeting.2 That study showed a 17-month overall survival improvement with docetaxel added to androgen-deprivation therapy in men with high-volume disease, from 32.2 months to 49.2 months (P = .0006).

“In this retrospective analysis of GETUG-AFU 15, the majority of patients were low volume, around 53%, and 80% of patients in the androgen-deprivation therapy–alone arm received docetaxel after castration resistance. As distinct from the CHAARTED study, we found that the median overall survival was not significantly different,” she said.

When patients in GETUG-AFU 15 were analyzed retrospectively according to disease volume, no significant difference was observed for low-volume disease between the two arms at a median follow-up of 81 months. Median overall survival was not reached with androgen-deprivation therapy alone and was 83.1 months for androgen-deprivation therapy plus docetaxel. In the high-volume disease group, median overall survival was 35.1 months vs 39 months, respectively. This represented a nonsignificant 4-month difference favoring docetaxel at a median follow-up of 84 months.

In a multivariate analysis, prognostic factors included the extent of metastases (high or low volume) and the level of alkaline phosphatase at baseline were independant prognostic factors for survival. Treatment arm was not significant.

There was no difference in overall survival in unselected patients with metastatic prostate cancer. In a retrospective analysis, no improvement was observed in patients with low-volume disease with the addition of docetaxel, and a nonsignificant difference of 4 months was observed in the high-volume disease group.

Possible explanations for the difference between the current results and those in the CHAARTED study include the increased use of salvage docetaxel in GETUG-AFU 15 and that the study was underpowered to detect a difference in the 183 patients with high-volume disease (91 on androgen-deprivation therapy alone and 92 on androgen-deprivation therapy plus docetaxel).

When available, results of the STAMPEDE trial will be considered in the context of both CHAARTED and GETUG-AFU 15 to determine the best course of treatment, she said. ■

Disclosure: Dr. Gravis has served as a consultant or advisor to and traveled on behalf of Sanofi.

References

1. Gravis G, Boher JM, Joly F, et al: Androgen deprivation therapy plus docetaxel versus ADT alone for hormone-naive metastatic prostate cancer: Long-term analysis of the GETUG-AFU 15 phase III trial. 2015 Genitourinary Cancers Symposium. Abstract 140. Presented February 26, 2015.

2. Sweeney C, Chen, Y-H, Carducci MA, et al: Impact on overall survival with chemohormonal therapy versus hormonal therapy for hormone-sensitive newly metastatic prostate cancer: An ECOG-led phase III randomized trial. 2014 ASCO Annual Meeting. Abstract LBA2.


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GETUG-AFU 15 sought to improve outcomes in metastatic hormone-naive prostate cancer, but the study failed its primary objective,” noted formal discussant Eric J. Small, MD, of the University of California, San Francisco.

In the overall analysis of this previously published trial, with no...


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