A Living Interactive Systematic Review and Network Meta-Analysis on First-Line Treatment Options in Metastatic Castration Sensitive Prostate Cancer

The therapeutic landscape of metastatic castration-sensitive prostate cancer (mCSPC) is rapidly changing. Recently, two large randomized controlled trials studying different combinations of androgen receptor pathway inhibitors (ARPI), and docetaxel chemotherapy as add-on treatments to androgen deprivation therapy (ADT) have reported results. The PEACE-1 trial showed that the combination of abiraterone acetate and docetaxel doublet therapy postponed disease progression and improved overall survival in patients diagnosed with metastatic disease at initial presentation. ARASENS demonstrated similar results with improved overall survival in patients who received the combination of darolutamide and docetaxel doublet therapy compared to those who received docetaxel doublet only. The recent report from ARCHES showed consistent long-term survival benefit with the use of enzalutamide doublet in mCSPC patients. Moreover, prostate cancer is a heterogeneous disease with synchronous or high-volume patients at one end of the disease spectrum and metachronous or low-volume patients at the other end. Efficacy by volume of disease from ARASENS trial, mature survival data in low volume of disease from PEACE-1 trial, and long-term updated data from ENZAMET are now available. Therefore, treatment options, estimates of benefits and harms, and certainty in evidence have been updated. This update also includes overall survival data by prognostic subgroups (synchronous high volume, synchronous low volume, metachronous high volume, metachronous low volume) assessing the comparative effectiveness of contemporary systemic treatment options. This network meta-analysis (NMA) allows for comparing all treatments with each other, even if randomized controlled trials are not available for some treatment comparisons, and we keep it living and interactive to provide the most contemporary evidence as soon as new information becomes available.


INTERACTIVE, MODIFIED PRISMA

The search strategy has been developed in consultation with an information specialist. The strategy is used to generate “auto” searches every month (from Medline, Embase and Cochrane Central Register of Controlled Trials [CENTRAL]). The numbers in the flowsheet are dynamically updated as new studies are considered for inclusion. Users can click the colored boxes for additional details.

How to use this flowsheet? Video demonstration

SUMMARY TABLES


INTERACTIVE TABLE

The interactive table summarizes study characteristics, population characteristics and results from the clinical trials included in this systematic review and meta-analysis. This table is dynamically updated as new studies are included in the living review. Users can select filter options to view only studies with certain characteristics or interactively construct the results table from the available menu.

How to use this table? Video demonstration


RESULT TABLE

Result Table Findings.



PAIRWISE META-ANALYSIS

Results are summarized as forest plots for primary analysis, sensitivity analysis and subgroup pairwise meta-analysis. Users can choose to view results for their outcome of interest using the dropdown menu (“Select outcome”). Pairwise analysis is limited to trials evaluating doublet therapies as compared to ADT and triplet therapies as compared to D+ADT. Primary analysis includes overall patient population.


Primary Analysis


Sensitivity Analysis


Subgroup Analysis


NETWORK META-ANALYSIS

Results are summarized as forest plots for primary analysis and sensitivity network meta-analysis. Users can choose to view results for their outcome of interest using the dropdown menu (“Select outcome”).


Primary Analysis


Secondary Analyses


SUMMARY OF FINDINGS: PAIRWISE META-ANALYSIS

The Summary of Findings (SoF) table is designed to summarize the key results of pairwise meta-analysis and to evaluate confidence in the estimates of effect. This table summarizes results for patient-important outcomes for all treatment options investigated in included trials as compared to control, in mCSPC. Users can select their outcome of interest from the left-hand panel by clicking on it and enter any baseline risk for that outcome, to visualize the absolute risk differences due to treatment.

Choose measure of effect and denominator for absolute effect.


SUMMARY OF FINDINGS: NETWORK META-ANALYSIS

The Summary of Findings (SoF) table is designed to display multiple comparisons in an interactive manner. All possible combinations in network meta-analysis can be compared using this framework. Users can interactively select or deselect SoF for a given clinical outcome by clicking the outcome of interest from the left-hand panel. Users can also enter any baseline risk for an outcome, to visualize the absolute risk differences due to treatment. Clicking on any of the colored boxes displays details of that effect estimate as well as its associated certainty of evidence assessment.

Choose reference treatment, measure of effect, and denominator for absolute effect.


EVIDENCE MAP

The evidence map visually summarizes the evidence for available treatment comparisons and identifies evidence gaps that warrant future research. User can select a treatment option of interest from the dropdown to visualize whether it is comparable, beneficial or harmful (color), certainty of evidence (size of the circle) as compared to other treatment options in the network. Empty slots (no circles) denote the complete lack of evidence (either direct or indirect).


PUBLICATIONS

Full-text publications

First-line Systemic Treatment Options for Metastatic Castration-Sensitive Prostate Cancer: A Living Systematic Review and Network Meta-analysis JAMA Oncology. 2023 May 1;9(5):635-645
Irbaz Bin Riaz, Syed Arsalan Ahmed Naqvi, Huan He, Noureen Asghar, Rabbia Siddiqi, Hongfang Liu, Parminder Singh, Daniel S Childs, Praful Ravi, Syed A Hussain, Mohammad Hassan Murad, Stephen A Boorjian, Christopher Sweeney, Eliezer M Van Allen, Alan H Bryce
PMID: 36862387   DOI: 10.1001/jamaoncol.2022.7762

Abstracts presentations

The role of volume of disease for treatment selection in patients with metastatic castration-sensitive prostate cancer (mCSPC): A living meta-analysis. 2023 ASCO Annual Meeting | June 01, 2023 | 5088-5088
Syed Arsalan Ahmed Naqvi, Irbaz Bin Riaz, Huan He, Manal Imran, Jacob Orme, Daniel S Childs, Praful Ravi, Syed A. Hussain, Parminder Singh, Alan Haruo Bryce
DOI: 10.1200/JCO.2023.41.16_suppl.5088

A living interactive systematic review and network meta-analysis evaluating systemic therapies in metastatic castration-sensitive prostate cancer (mCSPC) 2023 ASCO Genitourinary Cancers Symposium | February 20, 2023 | 193-193
Irbaz Bin Riaz, Syed Arsalan Ahmed Naqvi, Huan He, Rabbia Siddiqi, Noureen Asghar, Praful Ravi, Syed A. Hussain, Parminder Singh, Alan Haruo Bryce
DOI: 10.1200/JCO.2023.41.6_suppl.193

Deep prostate-specific antigen response and overall survival in patients with metastatic castration-sensitive prostate cancer: A systematic review and meta-analysis. 2023 ASCO Genitourinary Cancers Symposium February 20, 2023 195-195
Syed Arsalan Ahmed Naqvi, Irbaz Bin Riaz, Manal Imran, Muhammad Daim Bin Zafar, Kunwer Sufyan Faisal, Zaryab Bin Riaz, Parminder Singh, Alan Haruo Bryce
DOI: 10.1200/JCO.2023.41.6_suppl.195

First-line treatment options in metastatic castration-sensitive prostate cancer: A systematic review and network meta-analysis. 2022 ASCO Genitourinary Cancers Symposium February 20, 2022 132-132
Irbaz Bin Riaz, Syed Arsalan Ahmed Naqvi, Waleed Ikram, Rabbia Siddiqi, Noureen Asghar, Kaneez Zahra Rubab Khakwani, Atiqa Khalid, Syed A. Hussain, Parminder Singh, Alan Haruo Bryce
DOI: 10.1200/JCO.2022.40.6_suppl.132

Indirect comparisons of triplet therapy as compared to novel hormonal therapy doublets in patients with metastatic castration sensitive prostate cancer. 2022 ASCO Annual Meeting I June 01, 2022 5083-5083
Syed Arsalan Ahmed Naqvi, Zaryab Bin Riaz, Anum Riaz, Mahnoor Islam, Rabbia Siddiqi, Waleed Ikram, Muhammad Daim Bin Zafar, Parminder Singh, Irbaz Bin Riaz, Alan Haruo Bryce
DOI: 10.1200/JCO.2022.40.16_suppl.5083

Triplet therapy in metastatic castration-sensitive prostate cancer: A systematic review and meta-analysis. 2022 ASCO Genitourinary Cancers Symposium February 20, 2022 136-136
Syed Arsalan Ahmed Naqvi, Zaryab Bin Riaz, Anum Riaz, Mahnoor Islam, Rabbia Siddiqi, Waleed Ikram, Muhammad Ali Jafar, Parminder Singh, Praful Kumar Ravi, Irbaz Bin Riaz, Alan Haruo Bryce
DOI: 10.1200/JCO.2022.40.6_suppl.136