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Comparative Study
. 2024 Dec 28;43(1):51.
doi: 10.1007/s00345-024-05388-1.

Androgen receptor pathway inhibitors vs. docetaxel chemotherapy for metastatic hormone-sensitive and first-line castration resistant prostate cancer

Mike Wenzel  1 , Benedikt Hoeh  2 , Clara Humke  2 , Cristina Cano Garcia  2 , Carolin Siech  2 , Thomas Steuber  3 , Markus Graefen  3 , Miriam Traumann  2 , Luis Kluth  2 , Felix K H Chun  2 , Philipp Mandel  2   3
Affiliations
Comparative Study

Androgen receptor pathway inhibitors vs. docetaxel chemotherapy for metastatic hormone-sensitive and first-line castration resistant prostate cancer

Mike Wenzel et al. World J Urol. .

Abstract

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.

Keywords: ARPI; Apalutamide; Enzalutamide; mCRPC, high volume; mHSPC.

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Conflict of interest statement

Declarations. Competing interests: Financial disclosures and Conflicts of interest: Mike Wenzel receives speaker honoraria or is consultant for Accord, Johnsen&Johnsen, Pfizer, MSD, Astra Zeneca, Ipsen, Benedikt Hoeh receives speaker honoraria or is consultant for Johnsen&Johnsen and Ipsen, Thomas Steuber receives speaker honoraria or is consultant for Amgen, Astellas, Astra Zeneca, Bayer, Johnson & Johnson, MSD, Novartis, Pfizer, Proteomedics, Sanofi, Markus Graefen receives speaker honoraria or is consultant for Intuitive Surgical, Metronic, Ipsen, Astellas, Johnson & Johnson und Takeda, Felix Chun receives speaker honoraria or is consultant for Astellas, AstraZeneca, Bayer, Johnson & Johnson, Lumenis, Molecular Health, Olympus, Pfizer, Philipp Mandel receives speaker honoraria or is consultant for AMGEN, Astellas, AstraZeneca, Bayer, IPSEN, Johnson & Johnson, MSD, Novartis, Orion, Pfizer. Conflicts of interest: Mike Wenzel receives speaker honoraria or is consultant for Accord, Johnsen&Johnsen, Pfizer, MSD, Astra Zeneca, Ipsen, Benedikt Hoeh receives speaker honoraria or is consultant for Johnsen&Johnsen and Ipsen, Thomas Steuber receives speaker honoraria or is consultant for Amgen, Astellas, Astra Zeneca, Bayer, Johnson & Johnson, MSD, Novartis, Pfizer, Proteomedics, Sanofi, Markus Graefen receives speaker honoraria or is consultant for Intuitive Surgical, Metronic, Ipsen, Astellas, Johnson & Johnson und Takeda, Felix Chun receives speaker honoraria or is consultant for Astellas, AstraZeneca, Bayer, Johnson & Johnson, Lumenis, Molecular Health, Olympus, Pfizer, Philipp Mandel receives speaker honoraria or is consultant for AMGEN, Astellas, AstraZeneca, Bayer, IPSEN, Johnson & Johnson, MSD, Novartis, Orion, Pfizer. Consent to participate: No informed consent was necessary according to the approval of the study by the ethic committee.

Figures

Fig. 1
Fig. 1
Kaplan Meier curves depicting time to metastatic castration resistant prostate cancer (CRPC, A) and overall survival (B) according treatment for high volume metastatic hormone-sensitive prostate cancer (mHSPC) stratified according to docetaxel vs. androgen receptor pathway inhibitor (ARPI)
Fig. 2
Fig. 2
Kaplan Meier curves depicting time to metastatic castration resistant prostate cancer (CRPC, A) and overall survival (B) according treatment for metastatic hormone-sensitive prostate cancer (mHSPC) stratified according to docetaxel vs. androgen receptor pathway inhibitor (ARPI)
See this image and copyright information in PMC

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