Comparison of doublet and triplet therapies for metastatic hormone-sensitive prostate cancer: A systematic review and network meta-analysis

Lei Wang; Chunxing Li; Zichen Zhao; Xiaojian Li; Chong Tang; Zhenpeng Guan; Feng Sun; Jin Gu; Ningchen Li

doi:10.3389/fonc.2023.1104242

Comparison of doublet and triplet therapies for metastatic hormone-sensitive prostate cancer: A systematic review and network meta-analysis

Front Oncol. 2023 Mar 7:13:1104242. doi: 10.3389/fonc.2023.1104242. eCollection 2023.

Authors

Lei Wang¹, Chunxing Li², Zichen Zhao¹, Xiaojian Li¹, Chong Tang³, Zhenpeng Guan³, Feng Sun⁴, Jin Gu^{5

6}, Ningchen Li¹

Affiliations

¹ Wu Jieping Urology Center, Peking University Shougang Hospital, Beijing, China.
² Department of Pharmacy, Aerospace Center Hospital, Beijing, China.
³ Department of Orthopedics, Peking University Shougang Hospital, Beijing, China.
⁴ Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.
⁵ Gastrointestinal Cancer Center, Peking University Cancer Hospital, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing, China.
⁶ Department of Gastrointestinal Surgery, Peking University Shougang Hospital, Beijing, China.

Abstract

Background: The best choice of first-line treatment for metastatic hormone-sensitive prostate cancer (mHSPC) is unclear. We aimed to compare the effectiveness and safety determined in randomized clinical trials of doublet and triplet treatments for mHSPC.

Methods: Medline, Embase, Cochrane Central and ClinicalTrials.gov were searched from inception through July 01, 2022. Eligible studies were phase III randomized clinical trials evaluating androgen deprivation treatment (ADT) alone, doublet therapies [ADT combined with docetaxel (DOC), novel hormonal agents (NHAs), or radiotherapy (RT)], or triplet therapies (NHA+DOC+ADT) as first-line treatments for mHSPC. Outcomes of interest included overall survival (OS), progression-free survival (PFS) and grades 3-5 adverse events (AEs). Subgroup analyses were performed based on tumor burden. The effects of competing treatments were assessed by Bayesian network meta-analysis using R software.

Results: Ten trials with 12,298 patients comparing nine treatments were included. Darolutamide (DARO) +DOC+ADT ranked best in terms of OS benefits (OR 0·52 [95% CI 0·39-0·70]), but its advantages were all statistically insignificant compared with other therapy options except for DOC+ADT (OR 0·68 [95% CI 0·53-0·88]) and RT+ADT (OR 0·57 [95% CI 0·40-0·80]). In terms of PFS, enzalutamide(ENZA)+DOC+ADT (OR 0·32 [95% CI 0·24-0·44]) and abiraterone and prednisone (AAP) +DOC+ADT (OR 0·33 [95% CI 0·25-0·45]) ranked best. For patients with high volume disease (HVD), low volume disease (LVD), and visceral metastases, the optimal therapies were AAP+DOC+ADT (OR 0·52 [95% CI 0·33-0·83]), apalutamide+ADT (OR 0·52 [95% CI 0·26-1·05]) and DARO+DOC+ADT (OR 0·42 [95% CI 0·13-1·34]), respectively. For safety, AAP+DOC+ADT (OR 3·56 [95% CI 1·51-8·43]) ranked worst with the highest risk of grade 3-5 AEs.

Conclusions: Triple therapies may further improve OS and PFS but may be associated with a decrease in safety. Triplet therapies could be suggested for HVD patients, while doublet combinations should still be preferred for LVD patients.

Systematic review registration: https://www.crd.york.ac.uk/PROSPEROFILES/303117_STRATEGY_20220202.pdf, identifier CRD4202303117.

Keywords: chemotherapy; combination therapy; hormonal therapy; prostate cancer; radiation therapy.

Publication types

Systematic Review