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Addition of docetaxel to androgren deprivation confers durable OS benefit for metastatic prostate cancer
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BARCELONA, Spain — The addition of upfront docetaxel chemotherapy to androgen deprivation therapy conferred durable, clinically significant benefit for men with low- and high-burden metastatic prostate cancer, according to results of the randomized phase 3 STAMPEDE trial presented at European Society for Medical Oncology Congress.
“Docetaxel [in combination with] androgen deprivation therapy improves OS and failure-free survival in newly diagnosed metastatic prostate cancer regardless of metastatic burden,” Nicholas W. James, PhD, BSc, MB, BS, FRCP, FRCR, consultant in clinical oncology at Queen Elizabeth Hospital in Birmingham, England, and professor of clinical oncology at University of Birmingham, said during his presentation. “It should now be considered as a first-line option alongside [androgen receptor]-targeting agents for all [patients with de novo metastatic prostate cancer] regardless of stratification for disease burden.”
Previous results from the STAMPEDE trial showed upfront docetaxel improved OS for men starting long-term ADT after median follow-up of 3.5 years.
Clarke and colleagues reported long-term outcomes after a median 6.5 years of follow-up among 1,086 men with metastatic prostate cancer who were randomly assigned to the current standard of care alone (n = 724) or with docetaxel (n = 362).
OS served as the primary endpoint. Researchers also evaluated whether the benefit of adding docetaxel depended on metastatic burden, as previous trials had suggested.
Results showed that the addition of docetaxel to ADT significantly improved median OS (59.1 months vs. 43.1 months; HR = 0.81; 95% CI, 0.69-0.95).
Overall, 494 men who received standard-of-care treatment died, a 41% increase since the previous report.
Additionally, researchers found no evidence of a difference in OS benefit with docetaxel between men with low disease burden (HR = 0.76; 95% CI, 0.54-1.07) or high disease burden (HR = 0.81; 95% CI, 0.64-1.02).
The addition of docetaxel also improved failure-free survival (HR=0.66; 95% CI, 0.57-0.76) and PFS (HR=0.69; 95% CI, 0.59-0.81), with no difference in outcomes between the metastatic burden subgroups.
Further, docetaxel did not increase the rate of grade 3 to grade 5 adverse events after 1 year compared with standard of care (27% vs. 28%).
“This analysis does not support the presence of a volume effect on docetaxel effect in men with newly diagnosed metastatic prostate cancer,” James said. “Metastatic burden is, however, prognostic, which is consistent with what we have seen before.” – by John DeRosier
Reference:
Clarke NW, et al. Abstract 844O; Presented at: European Society for Medical Oncology Congress; Sept. 27-Oct. 1, 2019; Barcelona, Spain.
Disclosures: Astellas, Clovis, Janssen, Medical Research Council, Novartis, Pfizer and Sanofi funded this study. James reports consultant roles with Novartis and Sanofi and consultant/speakers bureau roles with, as well as research funding and travel expenses from, Janssen. Please see the abstract for all other authors’ relevant financial disclosures.
Perspective
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Karim Fizazi, MD, PhD
We have learned two main points from this updated analysis. First, the reduction in risk for death from docetaxel is less than 20%. Second, the effect of docetaxel seems to be similar according to the burden of disease.
HR for OS was 0.81, or just a 19% reduction for the risk for death. That’s good, but perhaps we can do better.
One part of this abstract compared high-burden vs. low-burden disease. Across the board, PFS, failure-free survival, prostate cancer-specific survival — whichever one you are looking at — you don’t see any real trend in the effectiveness of docetaxel by burden of disease. Even with OS, you don’t see any real trend. The HR seems to be a bit better — 0.76 for low-burden disease and 0.81 for high-burden disease — but having said that, we know the difference was not significant because the number of patients was too low or because docetaxel was not potent enough.
For the last 3 years, [there has been debate] about whether docetaxel should be given in low-volume M1 disease. To be honest, I don’t think that’s a real debate. If you look at next-generation androgen receptor targeting, the drugs work across the board regardless of low- or high-burden disease. You don’t see a big difference whether the patients have two metastases, four metastases or six metastases. These drugs just work and are improving survival and postponing death.
For M1 castration-resistant disease, again, docetaxel reduced risk for death by less than 20%. Androgen receptor targeting drugs reduce that same risk by about 35%.
Besides access and cost — and we have seen access be similar across the board for patients — I don’t see any real good reason to choose docetaxel over androgen receptor targeting.
Docetaxel works, but not very well. … I think we need to clarify the optimal treatment [for M1 relapse after local treatment].
I’ll be very happy to revise this opinion if ongoing trials eventually show that three drugs are better than two drugs. Hopefully we will know in the next few years.
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