Enzalutamide plus ADT is part of SoC in mHSPC across all patient subgroups
The incidence of mHSPC is increasing, thanks to earlier diagnosis and screening recommendations.1 This rise is expected to incur substantial burden due to the long duration of the disease.1,2 Although mHSPC is less prevalent compared to nmHSPC (9.4 cases vs 73.6 cases per 100,000), it is more costly in terms of health care resource utilisation as well as loss of life due to premature deaths.1-3
In April 2023, ASCO issued new guidelines for the management of hormone-sensitive recurrent, advanced or metastatic PCa following updated data from the ENZAMET, ARCHES, ARASENS and PEACE-1 trials as well as results from a meta-analysis of triplet therapy (ARPI plus ADT plus docetaxel) and a network meta-analysis which compared ADT plus ARPI with ADT plus docetaxel.4
In this update, ASCO states the six different SoC regimens for the treatment of mHSPC, i.e., administration of ADT along with either docetaxel, abiraterone acetate, enzalutamide, apalutamide, or darolutamide, and triplet therapies (docetaxel plus abiraterone plus ADT and docetaxel plus darolutamide plus ADT).4
High-quality evidence supports the strong recommendation of ADT plus enzalutamide as first-line treatment in patients with de novo mHSPC or recurrence from prior therapies.4 Enzalutamide doublet therapy offers overall long-term survival benefits for patients with low-volume or high-volume disease, without docetaxel use, and previous use of ADT or orchiectomy, as well as significantly improved time to first subsequent antineoplastic therapy.4 The treatment algorithm is condensed in Figure 1.4
In April 2023, ASCO issued new guidelines for the management of hormone-sensitive recurrent, advanced or metastatic PCa following updated data from the ENZAMET, ARCHES, ARASENS and PEACE-1 trials as well as results from a meta-analysis of triplet therapy (ARPI plus ADT plus docetaxel) and a network meta-analysis which compared ADT plus ARPI with ADT plus docetaxel.4
In this update, ASCO states the six different SoC regimens for the treatment of mHSPC, i.e., administration of ADT along with either docetaxel, abiraterone acetate, enzalutamide, apalutamide, or darolutamide, and triplet therapies (docetaxel plus abiraterone plus ADT and docetaxel plus darolutamide plus ADT).4
High-quality evidence supports the strong recommendation of ADT plus enzalutamide as first-line treatment in patients with de novo mHSPC or recurrence from prior therapies.4 Enzalutamide doublet therapy offers overall long-term survival benefits for patients with low-volume or high-volume disease, without docetaxel use, and previous use of ADT or orchiectomy, as well as significantly improved time to first subsequent antineoplastic therapy.4 The treatment algorithm is condensed in Figure 1.4
Enzalutamide is strongly recommended for first-line treatment of mHSPC based on high-quality evidence4
Enzalutamide plus ADT shows the lowest absolute HR in OS benefit compared with ADT alone and other doublet treatments from a systematic review
Treatment of mHSPC has evolved from an ADT-alone to combination approach, including a variety of systemic treatments.5 Researchers from the Peter MacCallum Cancer Centre (Victoria, Australia) and University of Sheffield Medical School (UK) conducted a network meta-analysis of seven randomised and quasi-randomised controlled trials to review the best combination treatment approaches in patients with mHSPC.5
The analysis employed the Bayesian approach–according to the NICE framework–with risk of bias assessed using the Cochrane framework.5 Ranking of each treatment was calculated using Surface Under Cumulative Ranking (SUCRA).5
The treatment combinations were ADT plus either docetaxel, abiraterone acetate and prednisone, enzalutamide or apalutamide.5 ADT served as the common comparison arm for all treatment combination in the meta-analysis (Table 1).5
The analysis employed the Bayesian approach–according to the NICE framework–with risk of bias assessed using the Cochrane framework.5 Ranking of each treatment was calculated using Surface Under Cumulative Ranking (SUCRA).5
The treatment combinations were ADT plus either docetaxel, abiraterone acetate and prednisone, enzalutamide or apalutamide.5 ADT served as the common comparison arm for all treatment combination in the meta-analysis (Table 1).5
All four doublet treatment combinations demonstrated significantly improved OS; the lowest HR of 0.53 (95% CI; 0.37– 0.75) was observed in the enzalutamide plus ADT group in comparison with ADT alone (Figure 2).5 SUCRA estimated that the possibility of enzalutamide being the preferred treatment to prolong OS was 76.9%.5
In patients with low-volume disease, only enzalutamide plus ADT showed improved survival outcomes in comparison with ADT alone (HR 0.38; 95% CI; 0.20–0.68) (Figure 3).5 According to SUCRA estimates, the possibility of enzalutamide being the preferred treatment to prolong OS in patients with low-volume disease was 84.2%.5
All doublet combinations presented higher survival outcomes in comparison with ADT alone in patients with high-volume disease, with enzalutamide plus ADT presenting the lowest absolute HR in OS (HR 0.62; 95% CI; 0.40– 0.95) (Figure 3).5 Based on SUCRA estimates, the possibility of treatment preference in patients with high-volume disease was 54.4% for enzalutamide, 24.1% for apalutamide and 11.5% for abiraterone.5
All doublet combinations presented higher survival outcomes in comparison with ADT alone in patients with high-volume disease, with enzalutamide plus ADT presenting the lowest absolute HR in OS (HR 0.62; 95% CI; 0.40– 0.95) (Figure 3).5 Based on SUCRA estimates, the possibility of treatment preference in patients with high-volume disease was 54.4% for enzalutamide, 24.1% for apalutamide and 11.5% for abiraterone.5
The network meta-analysis suggested that doublet treatment with enzalutamide and ADT is more effective in delaying death of any cause in patients with mHSPC in comparison with docetaxel and ADT.5
Enzalutamide plus ADT confers superior survival benefit in patients with mHSPC in comparison with other doublet treatment combinations or ADT alone5
Abbreviations: ADT, androgen deprivation therapy; ARPI, androgen receptor pathway inhibitors; ASCO, American Society of Clinical Oncology; CI, confidence interval; HR, hazard ratio; mHSPC, metastatic hormone-sensitive prostate cancer; NICE, National Institute for Health and Care Excellence; nmHSPC, non-metastatic hormone-sensitive prostate cancer; OS, overall survival; PCa, prostate cancer; RP, radical prostatectomy; RT, radiation therapy; SoC, standard of care; UK, United Kingdom; vs, versus.
References:
References:
- Hamid AA, et al. Metastatic hormone sensitive prostate cancer: Toward an era of adaptive and personalised treatment. 2023 ASCO Educational Book. http://ascopubs.org/doi/full/10.1200/EDBK_390166. Accessed on 3 October 2023.
- Ko GC, et al. Comparing costs and health care resource utilization between nmHSPC and mHSPC patients: a retrospective claims analysis. J Manag Care Spec Pharm 2022;28:287-295.
- Yu M, et al. Disease burden of metastatic hormone sensitive prostate cancer (mHSPC) in China. Value in Health 2021;24(Suppl 1):S39-S40.
- Virgo KS, et al. Initial management of noncastrate advanced, recurrent, or metastatic prostate cancer: ASCO guideline update. J Clin Oncol 2023;10:843-846.
- Sathianathen NJ, et al. Indirect comparisons of efficacy between combination approaches in metastatic hormone-sensitive prostate cancer: A systematic review and network meta-analysis. Eur Urol 2020;77:365-372.
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