Efficacy and safety of triple or dual therapies for metastatic hormone-sensitive prostate cancer: a systematic review and Bayesian network meta-analysis

Abstract

Aim: To compare triple and dual therapies for efficacy and safety in metastatic hormone-sensitive prostate cancer (mHSPC). Methods: A Bayesian network meta-analysis was conducted to indirectly compare overall survival, progression-free survival and adverse events in mHSPC patients with triple and dual therapies. Results: Triple and dual therapies were related to considerably higher overall survival than androgen-deprivation therapy (ADT), and darolutamide + docetaxel + ADT (hazard ratio [HR]: 0.54; 95% CI: 0.39–0.76; P score = 0.89) emerged as the best option. In terms of progression-free survival, abiraterone + prednisolone + docetaxel + ADT (HR: 0.33; 95% CI: 0.19–0.53; P score = 0.92) emerged as the best option. Apalutamide + ADT had the lowest odds of adverse events. Conclusion: Triple therapies were particularly effective in mHSPC patients, but the incidence of adverse events was significantly high.

Tweetable abstract

A network meta-analysis was used to indirectly compare overall survival, progression-free survival and adverse events in metastatic hormone-sensitive prostate cancer patients receiving triple and dual therapies. Triple therapies have shown significant benefits but their safety should be closely monitored.

Summary points

• The phase III PEACE-1 (NCT01957436) and ARASENS (NCT02799602) trials combined novel androgen signaling inhibitors with chemotherapeutics to treat metastatic hormone-sensitive prostate cancer (mHSPC) and showed long-term survival benefits.

• The phase III trials CHART (NCT03520478) combined the novel endocrine drug rezvilutamide (SHR3680) also recently released the latest data. Rezvilutamide plus androgen deprivation therapy (ADT) significantly improved radiological progression-free survival and overall survival compared with high-volume mHSPC patients with a tolerable safety profile.

• Here, network meta-analyses were applied to compare not only which treatment strategy was more advantageous between triple and dual therapies, but also within triple and dual therapies, as well as between novel androgen inhibitors and chemotherapeutic drugs.

• The majority of phase III clinical trials were controlled by ADT, so ADT was selected as the primary reference therapy for efficacy and safety.

• According to the published results of phase III clinical trials, overall survival and progression-free survival were selected as the main outcomes to judge the efficacy of each regimen.

• Clinical safety outcomes included all grades of adverse events and ≥3 grade adverse events.

• To increase the credibility of the network meta-analysis results, high- and low-volume subgroup and sensitivity analyses were carried out.

• In the network meta-analysis results, triple therapies were particularly effective in mHSPC patients, but the incidence of adverse effects was significantly increased. Rezvilutamide + ADT significantly improved the survival benefit of patients in the high-volume subgroup. Apalutamide+ ADT had the lowest incidence of adverse effects among all modalities and may be the most effective for low-volume mHSPC patients.

Keywords: :

• androgen receptor inhibitors
• docetaxel
• metastatic hormone-sensitive prostate cancer
• network meta-analysis
• treatment

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/fon-2022-1114

Author contributions

All authors participated in the interpretation of data and in critical revision and approval of the final version of the manuscript. J Jiang, Z Wang, Y Wang, J Bai, G Yang and H Wang were involved in study conception. J Jiang, Z Wang, H Ding, Y Zhang and Y Wang were involved in study design. J Jiang, Z Wang, Z Zhai and Z Dong were involved in data acquisition. J Jiang, Z Wang, Y Wang, J Bai and G Yang were involved in data analysis. J Jiang and Z Wang drafted the manuscript.

Financial disclosure

This work was supported by the National Natural Science Foundation of China (grant no. 81874088). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, stock ownership or options and expert testimony.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (grant no. 81874088).