First-line Systemic Treatment Options for Metastatic Castration-Sensitive Prostate Cancer

Riaz, Irbaz Bin; Naqvi, Syed Arsalan Ahmed; He, Huan; Asghar, Noureen; Siddiqi, Rabbia; Liu, Hongfang; Singh, Parminder; Childs, Daniel S; Ravi, Praful; Hussain, Syed A.; Murad, Mohammad Hassan; Boorjian, Stephen A.; Sweeney, Christopher J.; Allen, Eliezer M. Van; Bryce, Alan H.

doi:10.1001/jamaoncol.2022.7762

Cited by 38 publications

(29 citation statements)

References 45 publications

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“…First, patient compliance with chronic corticosteroid use on the ADT, abiraterone 1,000 mg, and prednisone 10 mg regimen must be weighed, especially considering side effects such as immunosuppression, metabolic dysfunction, musculoskeletal weakness, and psychological disturbance. Second, individual trials of triplet therapy regimens such as ADT, docetaxel, and darolutamide have demonstrated superior survival outcomes compared to some doublet regimens, 12,15 but questions linger regarding the impact that triplet therapy can have on patient health-related quality-of-life.…”

Section: Discussionmentioning

confidence: 99%

Estimating the Impact of the Inflation Reduction Act on the Out-of-Pocket Costs for Medicare Beneficiaries With Advanced Prostate Cancer

et al. 2023

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Introduction: Combination systemic therapy for advanced prostate cancer has reduced mortality, but high out-of-pocket costs impose financial barriers for patients. The Inflation Reduction Act's $2,000 out-of-pocket spending cap for Medicare's prescription drug benefit (Part D) can potentially lower out-of-pocket spending for beneficiaries starting in 2025. This study aims to compare out-ofpocket spending for commonly prescribed regimens for advanced prostate cancer before and after implementation of the Inflation Reduction Act. Methods: Medication regimens constructed to treat metastatic, hormone-sensitive prostate cancer consisted of baseline androgen deprivation therapy with traditional chemotherapy, androgen receptor inhibitors, and androgen biosynthesis inhibitors. Using 2023 Medicare Part B prices and the Medicare Part D plan finder, we estimated annual out-of-pocket costs under current law and under the Inflation Reduction Act's redesigned standard Part D benefit.Results: Under current law, out-of-pocket costs for Part D drugs ranged from $464 to $11,336 per year. Under the Inflation Reduction Act, annual out-of-pocket costs for 2 regimens remained unchanged: androgen deprivation therapy with docetaxel and androgen deprivation therapy with

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Section: Discussionmentioning

confidence: 99%

Estimating the Impact of the Inflation Reduction Act on the Out-of-Pocket Costs for Medicare Beneficiaries With Advanced Prostate Cancer

et al. 2023

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Section: Putting the Evidence Into Perspectivementioning

confidence: 99%

“…Multiple systematic reviews and network meta-analyses have attempted to indirectly compare ADT + ARPI + docetaxel vs. ADT + ARPI based on the randomized trials reviewed and also including other RCTs studying ADT + ARPI vs. ADT alone [ 36 , 37 , 38 , 39 , 40 , 41 ]. These meta-analyses have shown mixed results regarding the benefit of docetaxel [ 36 , 37 , 38 , 40 , 41 ] in the context of inherent biases in the absence of individual patient data for definitive comparisons. Although conducting a formal clinical trial to define the benefits of triplet therapy is ideal, there may be challenges to trial accrual given that ADT + ARPI is a highly effective backbone of treatment; many men with prostate cancer may be reluctant to be randomized to receive chemotherapy; and many clinicians may inherently favour either a doublet or triplet approach depending on patient characteristics and tumour risk factors.…”

Section: Putting the Evidence Into Perspectivementioning

confidence: 99%

Triplet Therapy in Metastatic Castrate Sensitive Prostate Cancer (mCSPC)—A Potential New Standard of Care

et al. 2023

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The treatment paradigm for metastatic castrate-sensitive prostate cancer (mCSPC) has evolved rapidly in the past decade with the approval of several life-prolonging therapies including docetaxel chemotherapy and multiple androgen receptor pathway inhibitors (ARPI) in combination with androgen deprivation therapy (ADT). Recently reported phase-three trials have demonstrated a survival benefit of upfront triplet therapy with ADT, docetaxel plus either abiraterone acetate or darolutamide when compared to ADT plus docetaxel alone. However, multiple questions including the incremental benefit of docetaxel to a combination of ADT and ARPI, the timing of ARPI, optimal patient selection for triplet therapy and clinical and genomic biomarkers still remain to be answered. Moreover, real-world data suggest suboptimal treatment intensification with many patients treated with ADT alone highlighting challenges in implementation. In this article, we review the phase-three data associated with triplet therapy in mCSPC. We also discuss the knowledge gaps that exist despite the completion of these studies and how ongoing studies are likely to change the paradigm in the near future. Finally, we provide a simple algorithm based on current data that clinicians can use in daily practice to select patients for appropriate treatment strategies.

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“…In this issue of JAMA Oncology, Riaz et al report the results of a “living” systematic review using the aggregate data from 10 identified RCTs that collectively enrolled a total of 11 043 patients, including those in the previously cited studies, for inclusion in a meta-analysis and network meta-analysis . The direct comparative meta-analysis of 8 of these trials showed that an ARSI-based doublet was associated with a considerably greater OS benefit than a docetaxel-based doublet when compared with ADT alone.…”

mentioning

confidence: 99%

Triplet Therapy in Metastatic Hormone-Sensitive Prostate Cancer—Calling Out the “Double Standard”

McHugh

Scher

2023

JAMA Oncol

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The gold standard for treating metastatic hormone-sensitive prostate cancer (mHSPC) has evolved rapidly in the past decade based on completed phase 3 randomized clinical trials (RCTs) of doublets showing that androgen deprivation therapy (ADT) in combination with docetaxel (ADT-D), reported first in the CHAARTED trial, and later with multiple androgen-receptor signaling inhibitors (ARSIs) were superior to ADT alone in improving the time to progression and prolonging life. [1][2][3][4][5] More recently, the PEACE-1 and ARASENS trials showed a similar overall survival (OS) benefit with a triplet regimen of ADT, docetaxel, and either abiraterone (ADT-D-AA) or darolutamide (ADT-D-Daro), the latter drug first approved by the US Food and Drug Administration for nonmetastatic castration-resistant disease. 6,7 In both trials, the triplet was superior to ADT-D, with ADT-D-Daro established as an US Food and Drug Administration-approved standard of care for mHSPC. Not formally studied was whether the triplet regimen confers a similar progression-free survival and OS advantage to an ADT-ARSI doublet, the more broadly used treatment in contemporary practice due to a more favorable safety profile and ease of administration.In this issue of JAMA Oncology, Riaz et al report the results of a "living" systematic review using the aggregate data from 10 identified RCTs that collectively enrolled a total of 11 043 patients, including those in the previously cited studies, for inclusion in a meta-analysis and network meta-analysis. 8 The direct comparative meta-analysis of 8 of these trials showed that an ARSI-based doublet was associated with a considerably greater OS benefit than a docetaxelbased doublet when compared with ADT alone. The result corroborates the academic consensus opinion favoring doublet selection reported in the Advanced Prostate Cancer Consensus Conference in 2021 and supports the recent removal of ADT-D as a first-line therapy for mHSPC in the National Comprehensive Cancer Network guidelines. 9,10 Going further and most notable in the overall population was the finding that mixed treatment comparisons of triplets with ADT-D-AA or ADT-D-Daro were not associated with an OS advantage compared with an ADT doublet with either apalutamide, enzalutamide, or abiraterone. This lack of association extended to progression-free survival, where there was no statistically significant improvement with an abiraterone-based triplet regimen relative to an enzalutamide-or apalutamide-based doublet, even when patients who received docetaxel in the EN-ZAMET, ARCHES, and TITAN trials were excluded, or disease burden classified as high or low volume based on the number of lesions on a radionuclide bone scan was considered, and the Related articleOpinion EDITORIAL

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First-line Systemic Treatment Options for Metastatic Castration-Sensitive Prostate Cancer

Cited by 38 publications

References 45 publications

Estimating the Impact of the Inflation Reduction Act on the Out-of-Pocket Costs for Medicare Beneficiaries With Advanced Prostate Cancer

Estimating the Impact of the Inflation Reduction Act on the Out-of-Pocket Costs for Medicare Beneficiaries With Advanced Prostate Cancer

Triplet Therapy in Metastatic Castrate Sensitive Prostate Cancer (mCSPC)—A Potential New Standard of Care

Triplet Therapy in Metastatic Hormone-Sensitive Prostate Cancer—Calling Out the “Double Standard”

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