Abstract
Background: To date, the efficacy of the androgen receptor inhibitors enzalutamide and apalutamide for the treatment of nonmetastatic castration-resistant prostate cancer (nmCRPC) has not been compared directly in a clinical trial setting. Indirect comparisons can be used to assess relative efficacy and provide important information to guide treatment decisions. PROSPER and SPARTAN were double-blind, randomized, placebo-controlled, phase III trials in patients with nmCRPC with overall similar study designs and inclusion and exclusion criteria. Using an anchored matching-adjusted indirect comparison, based on the final data from the PROSPER and SPARTAN studies, we assessed the comparative efficacy of enzalutamide and apalutamide, both plus androgen deprivation therapy. Methods: Using placebo as the common comparator, individual patient data from PROSPER were matched to the aggregate patient data from SPARTAN and efficacy endpoints from PROSPER were re-weighted accordingly. Patient baseline characteristics and endpoints were clinically and statistically tested to identify potential effect modifiers, according to National Institute for Health and Care Excellence guidelines. Hazard ratios for overall survival (OS), metastasis-free survival (MFS), and time to chemotherapy (TTCx) were re-estimated for PROSPER using weighted Cox proportional hazards models and indirectly compared with those of SPARTAN using a Bayesian network meta-analysis. Results: Estimated hazard ratios [95% credible interval (CrI)] for enzalutamide versus apalutamide were 0.80 (95% CrI 0.58-1.10) for OS, 0.94 (95% CrI 0.69-1.29) for MFS2, and 0.90 (95% CrI 0.63-1.29) for TTCx. Similar results were seen for sensitivity analyses conducted for OS and MFS. Bayesian probability analyses showed a 91.7% favoring enzalutamide for OS, 65.1% for MFS, and 71.4% for TTCx. Conclusions: The results of this matching-adjusted indirect comparison of final data from PROSPER and SPARTAN indicate comparable efficacy of enzalutamide and apalutamide with potentially a greater probability of longer MFS, OS, and TTCx in patients with nmCRPC treated with enzalutamide versus apalutamide.
| Original language | English (US) |
|---|---|
| Article number | 100510 |
| Journal | ESMO Open |
| Volume | 7 |
| Issue number | 3 |
| DOIs | |
| State | Published - Jun 2022 |
Funding
Medical writing support was provided by Lisa Carne, PhD, from Bioscript , and editorial assistance was provided by Folabomi Oladosu, PhD, Mashal Hussain, PhD, and Lauren Smith, BA (Hons), from Complete HealthVizion , funded by the study sponsors. Medical writing support was provided by Lisa Carne, PhD, from Bioscript, and editorial assistance was provided by Folabomi Oladosu, PhD, Mashal Hussain, PhD, and Lauren Smith, BA (Hons), from Complete HealthVizion, funded by the study sponsors. This work was supported by Astellas Pharma Inc. and Pfizer Inc., the co-developers of enzalutamide (no grant number). BT has received personal fees from Astellas, Bayer, Janssen, and Sanofi; and has served in an advisory role at Amgen, Ipsen, and Takeda. CNS has received personal fees from Janssen, Astellas, Clovis Oncology, AstraZeneca, Sanofi, Bayer, and Pfizer. MH has received grants, personal fees, and non-financial support from Bayer, Pfizer, and Genentech; personal fees and non-financial support from Astellas Pharma; personal fees from Physicians’ Education Resource, Sanofi/Genzyme, Phillips Gilmore Oncology, Daiichi Sankyo Company, Medical Learning Institute PeerView, Projects in Knowledge, and Research to Practice; and grants and personal fees have also been drawn from AstraZeneca. AG was a full-time employee of Astellas Pharma Global Development during the study. YL has received study funding and medical writing/editing support from Astellas; and medical writing/editing support from Complete HealthVizion and study analysis and medical writing support from IQVIA. RS was an employee of Pfizer Inc. at the time of study. HB was an employee of Astellas Pharma Global Development at the time of study, has stocks/ownership interest in Bristol Myers Squibb (BMS), Gilead, Bayer, and Abbot; and was paid travel/accommodation expenses by Astellas Pharma Global Development. MO received support for medical writing/editing from Astellas and Complete HealthVizion, and study funding from Astellas. FS received support for medical writing/editing from Astellas and Complete HealthVizion, and study funding from Astellas; grants which were directly made to Astellas, Bayer, Janssen, AstraZeneca, Sanofi, Pfizer, Myovant, BMS, and Merck; and consulting fees and honoraria from Astellas, Bayer, Janssen, AstraZeneca, Sanofi, Pfizer, Myovant, BMS, Merck, and Amgen. Researchers may request access to anonymized participant-level data, trial-level data, and protocols from Astellas sponsored clinical trials at www.clinicalstudydatarequest.com. For the Astellas criteria on data sharing, see: https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Astellas.aspx. This work was supported by Astellas Pharma Inc. and Pfizer Inc. , the co-developers of enzalutamide (no grant number).
Keywords
- apalutamide
- effect modifiers
- enzalutamide
- matching-adjusted indirect comparison
- network meta-analysis
- nonmetastatic castration-resistant prostate cancer
ASJC Scopus subject areas
- Oncology
- Cancer Research
