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Updated: May 8, 2025
Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
Published on: September 8, 2017
Androgen receptor pathway inhibitors vs. docetaxel chemotherapy for metastatic hormone-sensitive and first-line
Mike Wenzel1, Benedikt Hoeh2, Clara Humke2
1Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt am Main, Frankfurt, Germany. Mike.Wenzel@unimedizin-ffm.de.
Purpose:
No currently available phase III trial compared docetaxel vs. androgen receptor pathway inhibitors (ARPI) regarding cancer-control outcomes in metastatic hormone-sensitive prostate cancer (mHSPC). Moreover, few is known about the effect of sequential therapies in mHSPC and subsequent metastatic castration resistant prostate cancer (mCRPC).
Methods:
We relied on the FRAMCAP database and compared docetaxel vs. ARPI in mHSPC patients regarding time to mCRPC (ttCRPC) and overall survival (OS). Sensitivity analyses addressed high volume mHSPC patients. Finally, sequential therapies were compared regarding progression-free survival (PFS) and OS in first-line mCRPC.
Results:
Of 419 included mHSPC patients, 25% received docetaxel vs. 75% ARPI. ARPI patients were significantly older (71 vs. 66 years), and harbored lower baseline PSA (38 vs. 183 ng/ml, both p ≤ 0.002). Median ttCRPC was significantly longer for ARPI than for docetaxel-treated patients (30 vs. 17 months, hazard ratio [HR]: 0.49, p < 0.001). In OS analyses, ARPI patients also exhibited significantly longer OS, relative to docetaxel patients (96 vs. 50 months, HR: 0.67, p = 0.03). After multivariable adjustment in Cox regression models, no difference between both treatments remained in both analyses (all p > 0.05). In sensitivity analyses of high volume mHSPC patients only, also no ttCRPC or OS differences were observed for ARPI vs. docetaxel (all p > 0.05). Regarding sequential therapies, no PFS and OS differences were observed for all and specifically high volume mHSPC patients, when ARPI-ARPI vs. ARPI-docetaxel vs. docetaxel-ARPI treatments were compared (all p > 0.05).
Conclusion:
In real-world setting, ARPI treatment performs comparable to docetaxel chemotherapy in mHSPC. Therefore, docetaxel should only be used in triplet therapy. Moreover, no differences for sequential therapies of ARPI/docetaxel combinations in first-line mCRPC were observed.
Insights
Androgen receptor pathway inhibitors (ARPI) show comparable outcomes to docetaxel in metastatic hormone-sensitive prostate cancer (mHSPC). Sequential therapies with ARPI and docetaxel did not demonstrate significant differences in progression-free survival or overall survival for mCRPC patients.
Area of Science:
- Oncology
- Uro-oncology
- Prostate Cancer Research
Background:
- Metastatic hormone-sensitive prostate cancer (mHSPC) treatment landscape lacks direct comparisons between docetaxel and androgen receptor pathway inhibitors (ARPI).
- The impact of sequential therapies in mHSPC and subsequent metastatic castration-resistant prostate cancer (mCRPC) remains incompletely understood.
Purpose of the Study:
- To compare cancer-control outcomes, specifically time to mCRPC and overall survival (OS), between docetaxel and ARPI in mHSPC patients.
- To evaluate the effectiveness of sequential therapeutic strategies in mHSPC and mCRPC, including progression-free survival (PFS) and OS.
Main Methods:
- Retrospective analysis of the FRAMCAP database comparing docetaxel versus ARPI in mHSPC patients.
- Inclusion of sensitivity analyses for high-volume mHSPC patients.
- Comparison of sequential therapies (ARPI-ARPI, ARPI-docetaxel, docetaxel-ARPI) for first-line mCRPC treatment.
Main Results:
- While ARPI-treated patients were older and had lower baseline PSA, median time to mCRPC and OS were significantly longer compared to docetaxel.
- Multivariable adjustment revealed no significant differences in time to mCRPC or OS between ARPI and docetaxel in mHSPC.
- Sensitivity analyses in high-volume mHSPC patients and comparisons of sequential therapies in mCRPC showed no significant differences in PFS or OS.
Conclusions:
- In real-world settings, ARPI demonstrates comparable efficacy to docetaxel in mHSPC.
- Docetaxel should be considered primarily for triplet therapy in mHSPC.
- Sequential combinations of ARPI and docetaxel do not show differential outcomes in first-line mCRPC treatment.
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