To compare the effectiveness and safety of gonadotropin-releasing hormone (GnRH) antagonist monotherapy to combined androgen blockade (CAB) with a GnRH agonist and bicalutamide in patients with advanced hormone-sensitive prostate cancer (HSPC).

Methods

The study was conducted as KYUCOG-1401 trial (UMIN000014243) and enrolled 200 patients who were randomly assigned to either group A (GnRH antagonist monotherapy followed by the addition of bicalutamide) or group B (CAB by a GnRH agonist and bicalutamide). The primary endpoint was PSA progression-free survival. The secondary endpoints were the time to CAB treatment failure, radiographic progression-free survival, overall survival, changes in serum parameters, including PSA, hormones, and bone and lipid metabolic markers, and adverse events.

Results

PSA progression-free survival was significantly longer in group B (hazard ratio [HR], 95% confidence interval [CI]; 1.40, 1.01–1.95, p = 0.041). The time to CAB treatment failure was slightly longer in group A (HR, 95% CI; 0.80, 0.59–1.08, p = 0.146). No significant differences were observed in radiographic progression-free survival or overall survival. The percentage of patients with serum testosterone that did not reach the castration level was higher at 60 weeks (p = 0.046) in group A. No significant differences were noted in the serum levels of bone metabolic or lipid markers between the two groups. An injection site reaction was more frequent in group A.

Conclusions

The present results support the potential of CAB using a GnRH agonist and bicalutamide as a more effective treatment for advanced HSPC than GnRH antagonist monotherapy.

CONFLICT OF INTEREST STATEMENT

AY (Astellas Pharma Inc., Janssen Pharmaceutical K.K.), MS (Janssen Pharmaceutical K.K., AstraZeneca, Astellas Pharma Inc.), ME (Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Novartis Pharma K.K., Pfizer Japan Inc., Bristol-Myers Squibb Co., Janssen Pharmaceutical K.K., MSD K.K., Merck Biopharma Co., Ltd., AstraZeneca, Eisai Co., Ltd.), HideM (Janssen Pharmaceutical K.K., Chugai Pharmaceutical Co., Ltd.), HE (Astellas Pharma Inc.), TI (Astellas Pharma Inc., Janssen Pharmaceutical K.K.), TK (AstraZeneca, Merck Biopharma Co., Ltd.) have lecture fees, honoraria, or other fees from each entity.

MS (Daiichi Sankyo Co., Ltd.), ME (Bristol-Myers Squibb Co., Ono Pharmaceutical Co., Ltd., Eisai Co., Ltd., Taiho Pharmaceutical Co., Ltd., MSD K.K.), HideM (Janssen Pharmaceutical K.K.), TK (Janssen Pharmaceutical K.K., Shin Nippon Biomedical Laboratories, Ltd., Ono Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd., Sanofi K.K., Takeda Pharmaceutical Co., Ltd.) have research funds from each entity.

ME (Sanofi K.K., Bayer Yakuhin, Astellas Pharma Inc, Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd.), HideM (Kyowa Kirin Co., Ltd., Takeda Pharmaceutical Co., Ltd.) have scholarship (incentive) endowments or research grants from each entity.

FM, HiroM, NT, KK, ST, NF, KH, HS, TH, SS, YS, JK and SN have no COI to disclose.

Supporting Information

REFERENCES

1Shiota M, Eto M. Current status of primary pharmacotherapy and future perspectives toward upfront therapy for metastatic hormone-sensitive prostate cancer. Int J Urol. 2016; 23: 360–369.
10.1111/iju.13091
PubMed Web of Science® Google Scholar
2Debruyne F. Hormonal therapy of prostate cancer. Semin Urol Oncol. 2002; 20: 4–9.
10.1053/suro.2002.35051
PubMed Google Scholar
3Smith MR, Hussain M, Saad F, Fizazi K, Sternberg CN, Crawford ED, et al. Darolutamide and survival in metastatic, hormone-sensitive prostate cancer. N Engl J Med. 2022; 386: 1132–1142.
10.1056/NEJMoa2119115
CAS PubMed Web of Science® Google Scholar
4Blas L, Shiota M, Eto M. Current status and future perspective on the management of metastatic castration-sensitive prostate cancer. Cancer Treat Res Commun. 2022; 32:100606.
10.1016/j.ctarc.2022.100606
PubMed Google Scholar
5Swami U, Sinnott JA, Haaland B, Sayegh N, McFarland TR, Tripathi N, et al. Treatment pattern and outcomes with systemic therapy in men with metastatic prostate cancer in the real-world patients in the United States. Cancers (Basel). 2021; 13:4951.
10.3390/cancers13194951
CAS PubMed Web of Science® Google Scholar
6Klotz L, Boccon-Gibod L, Shore ND, Andreou C, Persson BE, Cantor P, et al. The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancer. BJU Int. 2008; 102: 1531–1538.
10.1111/j.1464-410X.2008.08183.x
CAS PubMed Web of Science® Google Scholar
7Tombal B, Miller K, Boccon-Gibod L, Schröder F, Shore N, Crawford ED, et al. Additional analysis of the secondary end point of biochemical recurrence rate in a phase 3 trial (CS21) comparing degarelix 80 mg versus leuprolide in prostate cancer patients segmented by baseline characteristics. Eur Urol. 2010; 57: 836–842.
10.1016/j.eururo.2009.11.029
CAS PubMed Web of Science® Google Scholar
8Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T, et al. EAU guidelines on prostate cancer. Part II: treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol. 2014; 65: 467–479.
10.1016/j.eururo.2013.11.002
CAS PubMed Web of Science® Google Scholar
9 Prostate Cancer Trialists' Collaborative Group. Maximum androgen blockade in advanced prostate cancer: an overview of the randomised trials. Lancet. 2000; 355: 1491–1498.
10.1016/S0140-6736(00)02163-2
CAS PubMed Web of Science® Google Scholar
10Akaza H, Hinotsu S, Usami M, Arai Y, Kanetake H, Naito S, et al. Combined androgen blockade with bicalutamide for advanced prostate cancer: long-term follow-up of a phase 3, double-blind, randomized study for survival. Cancer. 2009; 115: 3437–3445.
10.1002/cncr.24395
CAS PubMed Web of Science® Google Scholar
11Crawford ED, Shore ND, Moul JW, Tombal B, Schröder FH, Miller K, et al. Long-term tolerability and efficacy of degarelix: 5-year results from a phase III extension trial with a 1-arm crossover from leuprolide to degarelix. Urology. 2014; 83: 1122–1128.
10.1016/j.urology.2014.01.013
PubMed Web of Science® Google Scholar
12D'Oronzo S, Brown J, Coleman R. The role of biomarkers in the management of bone-homing malignancies. J Bone Oncol. 2017; 9: 1–9.
10.1016/j.jbo.2017.09.001
PubMed Web of Science® Google Scholar
13Kimura T, Koike Y, Aikawa K, Kimura S, Mori K, Sasaki H, et al. Short-term impact of androgen deprivation therapy on bone strength in castration-sensitive prostate cancer. Int J Urol. 2019; 26: 980–984.
10.1111/iju.14077
CAS PubMed Web of Science® Google Scholar
14Leeming DJ, Koizumi M, Qvist P, Barkholt V, Zhang C, Henriksen K, et al. Serum N-terminal propeptide of collagen type I is associated with the number of bone metastases in breast and prostate cancer and correlates to other bone related markers. Biomark Cancer. 2011; 3: 15–23.
10.4137/BIC.S6484
CAS PubMed Google Scholar
15Wakabayashi H, Nakajima K, Mizokami A, Namiki M, Inaki A, Taki J, et al. Bone scintigraphy as a new imaging biomarker: the relationship between bone scan index and bone metabolic markers in prostate cancer patients with bone metastases. Ann Nucl Med. 2013; 27: 802–807.
10.1007/s12149-013-0749-x
CAS PubMed Web of Science® Google Scholar
16Chao TY, Wu YY, Janckila AJ. Tartrate-resistant acid phosphatase isoform 5b (TRACP 5b) as a serum maker for cancer with bone metastasis. Clin Chim Acta. 2010; 411: 1553–1564.
10.1016/j.cca.2010.06.027
CAS PubMed Web of Science® Google Scholar
17Wolny-Rokicka E, Tukiendorf A, Wydmański J, Ostrowska M, Zembroń-Łacny A. Lipid status during combined treatment in prostate cancer patients. Am J Mens Health. 2019; 13: 1557988319876488.
10.1177/1557988319876488
Web of Science® Google Scholar
18Ozono S, Ueda T, Hoshi S, Yamaguchi A, Maeda H, Fukuyama Y, et al. The efficacy and safety of degarelix, a GnRH antagonist: a 12-month, multicentre, randomized, maintenance dose-finding phase II study in Japanese patients with prostate cancer. Jpn J Clin Oncol. 2012; 42: 477–484.
10.1093/jjco/hys035
PubMed Web of Science® Google Scholar
19Albertsen PC, Klotz L, Tombal B, Grady J, Olesen TK, Nilsson J. Cardiovascular morbidity associated with gonadotropin releasing hormone agonists and an antagonist. Eur Urol. 2014; 65: 565–573.
10.1016/j.eururo.2013.10.032
CAS PubMed Web of Science® Google Scholar
20Lopes RD, Higano CS, Slovin SF, Nelson AJ, Bigelow R, Sørensen PS, et al. Cardiovascular safety of degarelix versus leuprolide in patients with prostate cancer: the primary results of the PRONOUNCE randomized trial. Circulation. 2021; 144: 1295–1307.
10.1161/CIRCULATIONAHA.121.056810
PubMed Web of Science® Google Scholar

Citing Literature

Volume31, Issue4

April 2024

Pages 362-369

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iju15371-sup-0003-TableS2.docWord document, 100 KB	Table S2.
iju15371-sup-0004-TableS3.docxWord 2007 document , 40.7 KB	Table S3.

GnRH antagonist monotherapy versus a GnRH agonist plus bicalutamide for advanced hormone-sensitive prostate cancer; KYUCOG-1401

Abstract

Objectives

Methods

Results

Conclusions

CONFLICT OF INTEREST STATEMENT

Supporting Information

REFERENCES

Citing Literature

References

Information

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GnRH antagonist monotherapy versus a GnRH agonist plus bicalutamide for advanced hormone-sensitive prostate cancer; KYUCOG-1401

Abstract

Objectives

Methods

Results

Conclusions

CONFLICT OF INTEREST STATEMENT

Supporting Information

REFERENCES

Citing Literature

References

Related

Information