Comparison of Oncologic Outcomes between Two Alternative Sequences with Abiraterone Acetate and Enzalutamide in Patients with Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis

Abstract

Sequential treatment of androgen receptor axis targeted agents (ARAT), abiraterone acetate (ABI) and enzalutamide (ENZA), in metastatic castration-resistant prostate cancer (mCRPC) demonstrated some positive effects, but cross-resistances between ABI and ENZA that reduce activity have been suggested. Therefore, we conducted a meta-analysis to compare oncologic outcomes between the treatment sequences of ABI-ENZA and ENZA-ABI in patients with mCRPC. The primary endpoint was a combined progression-free survival (PFS), and the secondary endpoint was overall survival (OS). A total of five trials on 553 patients were included in this study. Each of the included studies was retrospective. In two studies including both chemo-naïve and post-chemotherapy mCRPC patients, for ABI-ENZA compared with ENZA-ABI, pooled hazard ratios (HRs) for PFS and OS were 0.37 (p < 0.0001; 95% confidence intervals (CIs), 0.23-0.60) and 0.64 (p = 0.10; 95% CIs, 0.37-1.10), respectively. In three studies with chemo-naïve mCRPC patients only, for ABI-ENZA compared with ENZA-ABI, pooled HRs for PFS and OS were 0.57 (p = 0.02; 95% CIs, 0.35-0.92) and 0.86 (p = 0.39; 95% CIs, 0.61-1.21), respectively. The current meta-analysis revealed that ABI-ENZA had a significantly more favorable oncological outcome, but the level of evidence was low. Therefore, large-scale randomized trials may be needed.

A randomized trial to evaluate the impact of exercise-based cardiac rehabilitation for the prevention of chemotherapy-induced cardiotoxicity in patients with breast cancer: ONCORE study protocol

“…Exercise, pointed out as a core component of these programs, has been shown to be safe and effective in mitigating side effects of breast cancer treatment, such as worsening quality of life [ 21 ], fatigue [ 20 ] or decreased physical function [ 42 ]. However, several studies have highlighted the need for more evidence on the cardioprotective effects of exercise in preventing cardiotoxicity and improving cardiopulmonary function [ 4 , 12 , 29 , 43 ].…”

“…Exercise programs are increasingly being recognized as an effective strategy to counteract adverse effects of cancer therapy [ 16 – 19 ]. While there is extensive evidence on the benefits of exercise to mitigate side effects such as fatigue [ 20 ] or to improve quality of life [ 21 ], evidence on the cardioprotective effects of exercise in breast cancer is still limited [ 4 , 22 – 24 ]. In addition to exercise programs, cardiac rehabilitation (CR) programs have proven beneficial to lessen the consequences of cardiovascular disease and reduce the risk of future events [ 25 ].…”

Treatment-Emergent Co-Morbidities and Survival in Patients With Metastatic Castration-Resistant Prostate Cancer Receiving Abiraterone or Enzalutamide

“…A pre-review counter is required for every payment of these two medications. These two medications shared similar strict criteria for pre-review counter, including the following ( Fizazi et al, 2012 ): Eastern Cooperative Oncology Group score of ≤2 ( Scher et al, 2012 ); poor response to at least two courses of docetaxel; and ( Chung et al, 2019 ) combination of abiraterone with prednisone or prednisolone. Every patient had to satisfy the first two criteria before they could obtain payment from national health insurance, and patients treated with abiraterone also had to satisfy the third criterion.…”

“…A comparison of the outcomes and adverse effects related to these two medications will help select the best medication, and this comparison is being extensively discussed. Several studies have compared cancer-related outcomes, including disease-specific survival, progression-free survival, and initial response rate; other studies have focused on comparing adverse effects between the two medications ( Kang et al, 2017 ; Chung et al, 2019 ; Komura et al, 2019 ; Markowski et al, 2021 ). A systematic review and a network meta-analysis of the treatments for chemotherapy-naive patients revealed that enzalutamide was superior to abiraterone/prednisone and sipuleucel-T with regard to radiographic progression-free survival ( McCool et al, 2018 ).…”

Effects of high-intensity training on the quality of life of cancer patients and survivors: a systematic review with meta-analysis

“…Sweegers et al (2018) and Buffat et al (2017) concluded that supervised exercise programmes can improve HRQoL and physical function 32 , 33 and are more beneficial than unsupervised interventions. Furthermore, in Hong et al (2019) meta-analysis, positive social functioning effects were found as a result of exercise, with the largest benefits seen when exercise sessions were 45 to 90 min in duration 34 . Moreover, physical cancer symptoms of fatigue, pain, insomnia, and dyspnoea also showed a decrease with exercise programmes 35 .…”