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Published in: Irish Journal of Medical Science (1971 -) 6/2023

Open Access 22-03-2023 | Prostate Cancer | Original Article

Role of apalutamide in the treatment landscape for patients with advanced prostate cancer: an expert opinion statement of European clinical practice

Authors: Martin Bögemann, Gaetano Facchini, Thomas Bauernhofer, Richard Cathomas, Evanguelos Xylinas, Bertrand Tombal

Published in: Irish Journal of Medical Science (1971 -) | Issue 6/2023

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Abstract

Background

Patients with advanced prostate cancer have a poor prognosis, and well-tolerated new treatment strategies are required to improve survival outcomes. Apalutamide is a novel androgen signalling inhibitor developed to be used in combination with continuous androgen deprivation therapy (ADT) for the treatment of patients with advanced prostate cancer. Based on evidence from two phase 3 pivotal clinical trials in non-metastatic castration-resistant (nmCRPC; SPARTAN) and metastatic hormone-sensitive prostate cancer (mHSPC; TITAN), ADT plus apalutamide significantly extends overall survival compared with the standard of care.

Aims

To provide practical recommendations to guide optimal use in the real-world setting as the use of apalutamide in clinical practice increases.

Methods

Expert opinion from a group of European physicians is presented here to educate on the use of apalutamide in combination with ADT in patients with mHSPC and patients with nmCRPC who are at risk of developing metastatic disease, focusing on practical considerations such as patient selection, monitoring, and management of side effects.

Results

In clinical practice, apalutamide in combination with ADT can be used in a broad patient population including patients with high and low volume/risk mHSPC, patients with de novo metastatic disease or metastases following treatment for localised disease, as well as older patients. Apalutamide in combination with ADT is well tolerated, with manageable side effects which do not impact health-related quality of life compared to ADT alone.

Conclusions

Real-world experience with apalutamide supports the efficacy and safety findings reported by the SPARTAN and TITAN clinical trials.
Literature
1.
go back to reference Sung H, Ferlay J, Siegel RL et al (2021) Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71:209–249CrossRefPubMed Sung H, Ferlay J, Siegel RL et al (2021) Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71:209–249CrossRefPubMed
2.
go back to reference Rebello RJ, Oing C, Knudsen KE et al (2021) Prostate cancer Nat Rev Dis Primers 7:9 Rebello RJ, Oing C, Knudsen KE et al (2021) Prostate cancer Nat Rev Dis Primers 7:9
4.
go back to reference GBD 2017 Disease and Injury Incidence and Prevalence Collaborators (2018) Global, regional, and national incidence, prevalence and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease study 2017. Lancet 392:1789–1858 GBD 2017 Disease and Injury Incidence and Prevalence Collaborators (2018) Global, regional, and national incidence, prevalence and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease study 2017. Lancet 392:1789–1858
5.
6.
go back to reference Fizazi K, Tran NP, Fein L et al (2017) Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med 377:352–360CrossRefPubMed Fizazi K, Tran NP, Fein L et al (2017) Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med 377:352–360CrossRefPubMed
7.
go back to reference Fizazi K, Tran NP, Fein L et al (2019) Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomized, double-blind, phase 3 trial. Lancet Oncol 20:686–700CrossRefPubMed Fizazi K, Tran NP, Fein L et al (2019) Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomized, double-blind, phase 3 trial. Lancet Oncol 20:686–700CrossRefPubMed
8.
go back to reference Francini E, Gray KP, Xie W et al (2018) Time of metastatic disease presentation and volume of disease are prognostic for metastatic hormone sensitive prostate cancer (mHSPC). Prostate 78:889–895CrossRefPubMedPubMedCentral Francini E, Gray KP, Xie W et al (2018) Time of metastatic disease presentation and volume of disease are prognostic for metastatic hormone sensitive prostate cancer (mHSPC). Prostate 78:889–895CrossRefPubMedPubMedCentral
9.
go back to reference James ND, Sydes MR, Clarke NW et al (2016) Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet 387(10024):1163–1177CrossRefPubMedPubMedCentral James ND, Sydes MR, Clarke NW et al (2016) Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet 387(10024):1163–1177CrossRefPubMedPubMedCentral
10.
11.
go back to reference James ND, Clarke NW, Cook A et al (2022) Abiraterone acetate plus prednisolone for metastatic patients starting hormone therapy: 5-year follow-up results from the STAMPEDE randomised trial (NCT00268476). Int J Cancer 151(3):422–434CrossRefPubMedPubMedCentral James ND, Clarke NW, Cook A et al (2022) Abiraterone acetate plus prednisolone for metastatic patients starting hormone therapy: 5-year follow-up results from the STAMPEDE randomised trial (NCT00268476). Int J Cancer 151(3):422–434CrossRefPubMedPubMedCentral
12.
go back to reference Armstrong AJ, Szmulewitz RZ, Petrylak DP et al (2019) ARCHES: a randomized, phase III study of androgen deprivation therapy with enzalutamide or placebo in men with metastatic hormone-sensitive prostate cancer. J Clin Oncol 37:2974–2986CrossRefPubMedPubMedCentral Armstrong AJ, Szmulewitz RZ, Petrylak DP et al (2019) ARCHES: a randomized, phase III study of androgen deprivation therapy with enzalutamide or placebo in men with metastatic hormone-sensitive prostate cancer. J Clin Oncol 37:2974–2986CrossRefPubMedPubMedCentral
13.
go back to reference Davis ID, Martin AJ, Stockler MR et al (2019) Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med 381:121–131CrossRefPubMed Davis ID, Martin AJ, Stockler MR et al (2019) Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med 381:121–131CrossRefPubMed
14.
go back to reference Chi KN, Agarwal N, Bjartell A et al (2019) Apalutamide for metastatic castration-sensitive prostate cancer. N Engl J Med 381:13–24CrossRefPubMed Chi KN, Agarwal N, Bjartell A et al (2019) Apalutamide for metastatic castration-sensitive prostate cancer. N Engl J Med 381:13–24CrossRefPubMed
15.
go back to reference Chi KN, Chowdhury S, Bjartell A et al (2021) Apalutamide in patients with metastatic castration-sensitive prostate cancer: final survival analysis of the randomized, double-blind, phase III TITAN study. J Clin Oncol 39:2294–2303CrossRefPubMed Chi KN, Chowdhury S, Bjartell A et al (2021) Apalutamide in patients with metastatic castration-sensitive prostate cancer: final survival analysis of the randomized, double-blind, phase III TITAN study. J Clin Oncol 39:2294–2303CrossRefPubMed
17.
go back to reference Fizazi K, Foulon S, Carles J et al (2022) Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design. Lancet 399(10336):1695–1707CrossRefPubMed Fizazi K, Foulon S, Carles J et al (2022) Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design. Lancet 399(10336):1695–1707CrossRefPubMed
18.
go back to reference Smith MR, Hussain M, Saad F et al (2022) Darolutamide and survival in metastatic, hormone-sensitive prostate cancer. N Engl J Med 24:1132–1142CrossRef Smith MR, Hussain M, Saad F et al (2022) Darolutamide and survival in metastatic, hormone-sensitive prostate cancer. N Engl J Med 24:1132–1142CrossRef
19.
go back to reference Fizazi K, Maldonado X, Foulon S et al (2021) A phase 3 trial with a 2x2 factorial design of abiraterone acetate plus prednisone and/or local radiotherapy in men with de novo metastatic castration-sensitive prostate cancer (mCSPC): first results of PEACE-1. J Clin Oncol 39(15 suppl):5000CrossRef Fizazi K, Maldonado X, Foulon S et al (2021) A phase 3 trial with a 2x2 factorial design of abiraterone acetate plus prednisone and/or local radiotherapy in men with de novo metastatic castration-sensitive prostate cancer (mCSPC): first results of PEACE-1. J Clin Oncol 39(15 suppl):5000CrossRef
20.
go back to reference Smith MR, Kabbinavar F, Saad F et al (2005) Natural history of rising serum prostate-specific antigen in men with castrate non-metastatic prostate cancer. J Clin Oncol 23:2918–2925CrossRefPubMed Smith MR, Kabbinavar F, Saad F et al (2005) Natural history of rising serum prostate-specific antigen in men with castrate non-metastatic prostate cancer. J Clin Oncol 23:2918–2925CrossRefPubMed
21.
go back to reference Smith MR, Saad F, Chowdhury S et al (2018) Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med 378:1408–1418CrossRefPubMed Smith MR, Saad F, Chowdhury S et al (2018) Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med 378:1408–1418CrossRefPubMed
22.
go back to reference Smith MR, Mehra M, Nair S et al (2020) Relationship between metastasis-free survival and overall survival in patients with nonmetastatic castration-resistant prostate cancer. Clin Genitourin Cancer 18(2):e180–e189CrossRefPubMed Smith MR, Mehra M, Nair S et al (2020) Relationship between metastasis-free survival and overall survival in patients with nonmetastatic castration-resistant prostate cancer. Clin Genitourin Cancer 18(2):e180–e189CrossRefPubMed
23.
24.
go back to reference Sternberg CN, Fizazi K, Saad F et al (2020) Enzalutamide and survival in nonmetastatic, castration-resistant prostate cancer. N Engl J Med 382:2197–2206CrossRefPubMed Sternberg CN, Fizazi K, Saad F et al (2020) Enzalutamide and survival in nonmetastatic, castration-resistant prostate cancer. N Engl J Med 382:2197–2206CrossRefPubMed
25.
go back to reference Fizazi K, Shore N, Tammela TL et al (2019) Darolutamide in nonmetastatic castration-resistant prostate cancer. N Engl J Med 380:1235–1246CrossRefPubMed Fizazi K, Shore N, Tammela TL et al (2019) Darolutamide in nonmetastatic castration-resistant prostate cancer. N Engl J Med 380:1235–1246CrossRefPubMed
26.
go back to reference Smith MR, Saad F, Chowdhury S et al (2021) Apalutamide and overall survival in prostate cancer. Eur Urol 79:150–158CrossRefPubMed Smith MR, Saad F, Chowdhury S et al (2021) Apalutamide and overall survival in prostate cancer. Eur Urol 79:150–158CrossRefPubMed
27.
go back to reference Agrawal N, Chowdbury S, Bjartell A et al (2021) Health-related quality of life and patient reported outcomes at final analysis of the TITAN study of apalutamide vs placebo in patients with metastatic castration-sensitive prostate cancer receiving androgen deprivation therapy. J Clin Oncol 39(15 suppl):5068 Agrawal N, Chowdbury S, Bjartell A et al (2021) Health-related quality of life and patient reported outcomes at final analysis of the TITAN study of apalutamide vs placebo in patients with metastatic castration-sensitive prostate cancer receiving androgen deprivation therapy. J Clin Oncol 39(15 suppl):5068
28.
go back to reference Chi KN, Saad F, Chowdbury S et al (2020) Prostate-specific antigen kinetics in patients with advanced prostate cancer treated with apalutamide: results from the TITAN and SPARTAN studies. J Clin Oncol 38(15 suppl):5541 Chi KN, Saad F, Chowdbury S et al (2020) Prostate-specific antigen kinetics in patients with advanced prostate cancer treated with apalutamide: results from the TITAN and SPARTAN studies. J Clin Oncol 38(15 suppl):5541
29.
go back to reference Small EJ, Chi KN, Chowdhury S et al (2022) Association between patient-reported outcomes and changes in prostate-specific antigen in patients with advanced prostate cancer treated with apalutamide in the SPARTAN and TITAN studies. J Clin Oncol 40(6 suppl):073 Small EJ, Chi KN, Chowdhury S et al (2022) Association between patient-reported outcomes and changes in prostate-specific antigen in patients with advanced prostate cancer treated with apalutamide in the SPARTAN and TITAN studies. J Clin Oncol 40(6 suppl):073
30.
go back to reference Parker C, Castro E, Fizazi K et al (2020) Prostate cancer: ESMO clinical practice guidelines for diagnosis, treatment, and follow-up. Ann Oncol 31:1119–1134CrossRefPubMed Parker C, Castro E, Fizazi K et al (2020) Prostate cancer: ESMO clinical practice guidelines for diagnosis, treatment, and follow-up. Ann Oncol 31:1119–1134CrossRefPubMed
31.
go back to reference Bjartell A, Ye D, Agarwal N et al (2020) Apalutamide plus androgen deprivation therapy for metastatic castration-sensitive prostate cancer in TITAN: outcomes in patients with de novo mCSPC vs progression to mCSPC after localised disease at diagnosis. Eur Urol Open Sci 19(Suppl 2):e863 Bjartell A, Ye D, Agarwal N et al (2020) Apalutamide plus androgen deprivation therapy for metastatic castration-sensitive prostate cancer in TITAN: outcomes in patients with de novo mCSPC vs progression to mCSPC after localised disease at diagnosis. Eur Urol Open Sci 19(Suppl 2):e863
32.
go back to reference Shen J, Chowdbury S, Agarwal N et al (2021) Apalutamide for advanced prostate cancer in older patients: combined analysis of TITAN and SPARTAN. Ann Oncol 32(suppl 5):S626–S677 Shen J, Chowdbury S, Agarwal N et al (2021) Apalutamide for advanced prostate cancer in older patients: combined analysis of TITAN and SPARTAN. Ann Oncol 32(suppl 5):S626–S677
34.
go back to reference Fendler WP, Weber M, Iravani A et al (2019) Prostate-specific membrane antigen ligand positron emission tomography in men with nonmetastatic castration-resistant prostate cancer. Clin Cancer Res 25:7448–7454CrossRefPubMed Fendler WP, Weber M, Iravani A et al (2019) Prostate-specific membrane antigen ligand positron emission tomography in men with nonmetastatic castration-resistant prostate cancer. Clin Cancer Res 25:7448–7454CrossRefPubMed
35.
go back to reference Lowentritt B, Pilon D, Khilfeh I et al (2022) Attainment of early, deep prostate-specific antigen response in metastatic castration-sensitive prostate cancer: a comparison of patients initiated on apalutamide or enzalutamide. J Clin Oncol 40(6 suppl):43CrossRef Lowentritt B, Pilon D, Khilfeh I et al (2022) Attainment of early, deep prostate-specific antigen response in metastatic castration-sensitive prostate cancer: a comparison of patients initiated on apalutamide or enzalutamide. J Clin Oncol 40(6 suppl):43CrossRef
36.
go back to reference Rathkopf DE, Scher HI (2018) Apalutamide for the treatment of prostate cancer. Exp Rev Anticancer Ther 18:823–836CrossRef Rathkopf DE, Scher HI (2018) Apalutamide for the treatment of prostate cancer. Exp Rev Anticancer Ther 18:823–836CrossRef
37.
go back to reference Tohi Y, Kataoka K, Miyai Y et al (2021) Apalutamide-associated skin rash in patients with prostate cancer: histological evaluation by skin biopsy. IJU Case Rep 4:299–302CrossRefPubMedPubMedCentral Tohi Y, Kataoka K, Miyai Y et al (2021) Apalutamide-associated skin rash in patients with prostate cancer: histological evaluation by skin biopsy. IJU Case Rep 4:299–302CrossRefPubMedPubMedCentral
38.
go back to reference Sagawa N, Watanabe Y, Mizuno Y et al (2020) A case of toxic epidermal necrolysis associated with apalutamide administration. J Cutan Immunol Allergy 3:134–135CrossRef Sagawa N, Watanabe Y, Mizuno Y et al (2020) A case of toxic epidermal necrolysis associated with apalutamide administration. J Cutan Immunol Allergy 3:134–135CrossRef
Metadata
Title
Role of apalutamide in the treatment landscape for patients with advanced prostate cancer: an expert opinion statement of European clinical practice
Authors
Martin Bögemann
Gaetano Facchini
Thomas Bauernhofer
Richard Cathomas
Evanguelos Xylinas
Bertrand Tombal
Publication date
22-03-2023
Publisher
Springer International Publishing
Published in
Irish Journal of Medical Science (1971 -) / Issue 6/2023
Print ISSN: 0021-1265
Electronic ISSN: 1863-4362
DOI
https://doi.org/10.1007/s11845-023-03303-y

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