OS benefit analysis of enzalutamide and abiraterone in chemotherapy-naïve patients with mCRPC: Real-world evidence

PCa is the leading cause of cancer-related death and the second most frequent cancer among men worldwide, with an estimated 1.4 million new cases and 375,000 deaths in 2020.1 Although PCa is considered a slow-growing neoplasm, progression into castration-resistant metastatic stage is associated with poor OS and decreased quality of life.1

The American Urology Association recommended abiraterone acetate or enzalutamide as first-line treatment for patients newly diagnosed with mCRPC; however, there are currently no phase 3 data providing a head-to-head comparison of these two treatments.2,3 To address the absence of data, specialists at the Duke Cancer Institute and Cedars-Sinai Medical Center USA, examined real-world evidence from a US national data set of chemotherapy-naïve patients with mCRPC.3

Anonymised OS data from 5,506 patients receiving first-line abiraterone acetate or enzalutamide in the US Centers for Medicare and Medicaid Services were subjected to Kaplan-Meier analysis and IPTW-adjusted Cox proportional-hazards models with subgroup OS analyses (Figure 1 ).3
Kaplan-Meier analysis indicated that patients receiving abiraterone acetate had a statistically significant shorter OS in comparison with patients who received enzalutamide as first-line treatment.3 When taking into account age, race, geographic region, socioeconomic status, and comorbidities, patients in the enzalutamide population presented with significantly longer OS in comparison with patients in the abiraterone acetate group (Figure 2).3 IPTW-adjusted median OS was significantly longer for enzalutamide in comparison with abiraterone acetate in the overall population and among patients 75 above years, of White race, as well as patients with baseline CVD, diabetes, both CVD and diabetes, renal disease, and across all socioeconomic level.3
The OS subgroup data supports the use of enzalutamide in elderly patients (aged 75 years and above) with CVD, diabetes, and renal disease comorbidities.3
Enzalutamide prolongs OS in patients with mCRPC based on real-world evidence3
Phase 3 trial demonstrated that enzalutamide plus ADT is effective and safe for Chinese men with mHSPC
ADT monotherapy or ADT plus a nonsteroidal anti-androgen agent remains a staple treatment in approximately 47–77% of patients with mHSPC despite the limited survival benefit.4 The ARCHES global study was a phase 3, double-blind, placebo-controlled trial to examine the role of treatment intensification using enzalutamide plus ADT in patients with mHSPC.4

A separate ARCHES study was conducted in China to investigate the benefit of enzalutamide plus ADT in Chinese men with HSPC.5 Twenty-seven centres participated in the study and 180 patients with mHSPC were recruited; 120 patients in the test group while the rest served as the control population (i.e. ADT plus placebo).5 The primary outcome was TTPP; the secondary outcomes include rPFS, time to first SSE, TTCR, rate of undetectable PSA, ORR, time to new antineoplastic therapy and the safety profile.5

Results showed that enzalutamide plus ADT reduced the risk of PSA progression by 87% in comparison with placebo plus ADT with a HR of 0.130 (95% CI; 0.076–0.222; p<0.0001) (Figure 3).5
Patients with mHSPC who received enzalutamide plus ADT also displayed a longer time to rPFS, castration resistance events and initiation of new antineoplastic therapy as well as undetectable PSA levels (Table 1).5
Enzalutamide plus ADT also reduced the time to new antineoplastic therapy by 78.6% versus placebo plus ADT (HR 0.214; 95% CI; 0.122–0.375; nominal p<0.0001) (Figure 4).5 No statistically significant observation was seen for the time to SSE and ORR 5
Both treatment arms displayed similar overall TEAE rates (Table 2),5 however a higher proportion of Grade 3 or 4 TEAEs and serious TEAEs were reported in the enzalutamide arm in comparison to the ADT alone arm which is consistent with the ARCHES global study.5 TEAEs of special interest such as hypertension, musculoskeletal events, fatigue and fracture were reported in approximately 10% of patients in both treatment arms.5
The clinical efficacy and safety findings in the China ARCHES study are consistent with the global ARCHES trial.4,5
Enzalutamide plus ADT confers a superior survival benefit in Chinese patients with mHSPC in comparison with ADT alone5

Abbreviations: ABI, abiraterone acetate; ADT, androgen deprivation therapy; CCI, Charlson Comorbidity Index; CI, confidence interval; cum cumulative; CVD, cardiovascular disease; ENZA, enzalutamide; ESMO, European Society for Medical Oncology; HR, hazard ratio; IPTW, inverse probability treatment-weighting; ITT, intent-to-treat; mHSPC, metastatic hormone-sensitive prostate cancer; n, number; NCI-CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; NE, not estimable; NR, not reached; ORR, objective response rate; OS, overall survival; PBO, placebo; PCa, prostate cancer; PSA, prostate-specific antigen; rPFS, radiographic progression-free survival; SES, socioeconomic status; SSE, symptomatic skeletal event; TEAE, treatmentemergent adverse event; TTCR; time to castration resistance; TTPP, time to PSA progression; USA, United States of America; US, United States.

References:

  1. Turco F, et al. Treatment landscape for patients with castration-resistant prostate cancer: Patient selection and unmet clinical needs. Res and Reports in Urol 2022;14:339-350.
  2. Lowrance W, et al. Updates to advanced prostate cancer: AUA/SUO guideline (2023). J Urol 2023;209:1082-1090.
  3. George DJ, et al. Real-world overall survival (OS) with enzalutamide (ENZ) and abiraterone acetate (ABI) in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). Presented at: European Society for Medical Oncology Congress 2023; 20–24 October 2023; Madrid, Spain. Poster 1827P.
  4. Armstrong AJ, et al. The efficacy of enzalutamide plus androgen deprivation therapy in oligometastatic hormone-sensitive prostate cancer: A post hoc analysis of ARCHES. Eur Urol 2023;84:229-241.
  5. Zhou F, et al. China ARCHES: A multicenter, phase 3, randomized, double-blind, placebo-controlled efficacy and safety trial of enzalutamide plus androgen deprivation therapy versus placebo plus androgen deprivation therapy in Chinese men with metastatic hormone-sensitive prostate cancer. Presented at: European Society for Medical Oncology Congress 2023; 20–24 October 2023; Madrid, Spain. Poster 1795P.

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