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Early docetaxel with ADT extended OS in metastatic prostate cancer
CHICAGO — The addition of docetaxel to initial androgen deprivation therapy significantly prolonged OS among men with metastatic, hormone-sensitive prostate cancer, according to results of a phase 3 study presented at the ASCO Annual Meeting.
“Ten years ago today, there were two plenary sessions showing docetaxel worked in the castration-resistant disease space,” researcher Christopher Sweeney, MBBS, medical oncologist at the Lank Center of Genitourinary Oncology at the Dana-Farber Cancer Institute, said during a press conference. “So we asked, if it worked in the late stage, will it work in the early stage?”
Sweeney and colleagues evaluated data from 790 patients with a median age of 63 years (range, 36-91 years), 89% of whom were non-Hispanic white. A majority of patients (98%) had an ECOG performance status of 0 or 1, 24% received prior radiotherapy and 24% underwent prostatectomy.
Researchers assigned patients 1:1 to ADT alone or ADT plus 75 mg/m2 docetaxel every 3 weeks within 4 months of ADT initiation.
Median follow-up was 29 months. By this time, 136 patients had died in the ADT arm, whereas 101 deaths occurred in the combination arm.
Median OS among patients who received docetaxel plus ADT was 57.6 months, compared with 44 months in the ADT alone arm (HR=0.61; 95% CI, 0.47-0.80).
In a subgroup analysis of 520 patients with high-extent disease, researchers observed a greater difference in survival among patients who did vs. did not receive additional docetaxel (49.2 months vs. 32.2 months).
A greater proportion of patients assigned docetaxel demonstrated a PSA ˂.2 ng/mL after 1 year (22.7% vs. 11.7%).
Patients assigned docetaxel plus ADT also demonstrated delayed median time to clinical progression (32.7 months vs. 19.8 months).
Of the 174 patients who progressed on the ADT-alone arm, 129 received docetaxel at the time of progression.
“Three quarters of these patients who progressed actually received the therapy that was used up front in the combination,” Sweeney said.
Adverse events associated with ADT plus docetaxel were grade 3 (4%) and grade 4 (2%) neutropenic fever and grade 3 sensory (1%) and motor (1%) neuropathy. One treatment-related death occurred in the combination arm.
“Upfront chemo-hormonal therapy prolongs OS in men with metastatic prostate cancer commencing testosterone suppression,” Sweeney said. “This is one of the biggest improvements in survival we have seen in a trial involving patients with an adult metastatic solid tumor.”
For more information:
Sweeney C. Abstract #LBA2. Presented at: ASCO Annual Meeting; May 30-June 3, 2014; Chicago.
Disclosure: The study was funded by the NCI. Researchers report consultant/advisory roles with and honoraria, other remuneration or research funding from Sanofi.
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This is an old-dog new-tricks question. This is now a generic drug that is available more broadly than ever before with reduced costs.
In prostate cancer, I’m not aware of a historical study that ever offered this magnitude of improvement in survival. Quite frankly, across all of solid tumors, this is almost an unprecedented improvement in median survival. This is the kind of thing that can be transformative for people.
The issue of toxicity is a big one, which leads us to the next chapter of our attempt to move to less toxic, even more effective therapies.
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The cardinal sins of prostate cancer care for every clinical state are the misapprehension of risk by both the patient and clinician, leading to the misapplication of therapy. We need to avoid doing that here, just as we do in interpreting any clinical trial in prostate cancer. We need to be able to identify the appropriate high-volume patients who are chemotherapy candidates, and we have to be able to identify those who should be spared chemotherapy because there is no proven survival benefit, at least at this juncture.
We need to develop a more quantitative, sophisticated model that balances disease number, disease volume and disease distribution to best identify the patients who will ultimately enjoy the highest survival benefit from early chemotherapy.
I would argue that the investigators have adequately shown that high-volume patients with castration-sensitive metastatic disease do benefit from upfront docetaxel, and it does appear to confer a survival benefit that is superior to docetaxel given at metastatic, castration-resistant disease. But there is insufficient data at this time, after 29 months of medial follow-up, to recommend that low-volume patients with castration-sensitive disease undergo chemotherapy.
We need to optimize the distinction between those who will benefit from chemotherapy and those who don’t. What we’re talking about here is essentially 4.2% of the overall prostate cancer population, and high-volume disease represents a fraction of that. We’re talking about a fraction of a relatively low proportion of patients.