Combination treatment in metastatic prostate cancer: is the bar too high or have we fallen short?

Chen, Kenneth; O’Brien, J; McVey, Aoife; Jenjitranant, Pocharapong; Kelly, Brian D.; Kasivisvanathan, Veeru; Lawrentschuk, Nathan; Murphy, Declan; Azad, Arun

doi:10.1038/s41585-022-00669-z

Cited by 15 publications

(17 citation statements)

References 63 publications

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“…The number of patients who received TI increased from 18.1% in 2016 to 56.1% in 2020, hugely attributed to the widespread adoption of NHA (from 10.5% in 2016 to 50.4% in 2020). In contrast, results from other series were less promising 12–14,22,23 . Ryan et al.…”

Section: Discussionmentioning

confidence: 93%

Far from the truth: Real‐world treatment patterns among newly diagnosed metastatic prostate cancer in the era of treatment intensification

et al. 2023

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ObjectivesReal‐world uptake of treatment intensification (TI) with novel hormonal agents (NHA) or chemotherapy as treatment of metastatic prostate cancer remains low outside of trial settings. We aim to report the prescription patterns and treatment outcomes of de novo metastatic hormone‐sensitive prostate cancer (mHSPC) in a tertiary institution.MethodsThis is a retrospective cohort study using real‐world data from a prospectively maintained prostate cancer registry. We selected patients newly diagnosed with mHSPC from January 2016 to December 2020. Clinicopathological parameters were recorded to determine their impact on prescription patterns.ResultsIn total, 585 patients with metastatic prostate cancer were identified. Prescription of NHA increased from 10.5% (2016) to 50.4% (2020), but that of chemotherapy declined. Factors associated with TI were (1) baseline health status: Charlson Comorbidity Index 0–2, ECOG 0–1, age ≤ 65, (2) disease burden: PSA (>400, CHAARTED high volume disease, p = 0.004), development of systemic complications and (3) physician factor: primary physician being uro‐oncologist and medical oncologist versus general urologist. Patients with TI had a longer mean time to castration‐resistant prostate cancer (45.0 vs. 32.5 months, HR 0.567, 95% CI: 0.441–0.730, p < 0.001) and overall survival (55.3 vs. 46.8 months, HR 0.612, 95% CI, 0.447–0.837, p = 0.001).ConclusionThis study demonstrated the trend of treatment prescription of mHSPC and factors contributing to the use of TI. TI improved mean time to CRPC and OS.

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Section: Discussionmentioning

confidence: 93%

Far from the truth: Real‐world treatment patterns among newly diagnosed metastatic prostate cancer in the era of treatment intensification

et al. 2023

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“…1 However, phase III trials have demonstrated a marked survival benefit for mCSPC if androgen deprivation therapy (ADT) is complemented with docetaxel chemotherapy or second-generation androgen receptor signaling inhibitors (ARSi). 2 Since 2014, such treatment doublets have been incorporated into clinical practice and guidelines, yet real-world evidence suggests a low rate of adoption, owing amongst others to limited drug access, concerns about the safety of doublets in the typically elderly and often frail mCSPC patient, and the lack of validated predictive markers. 2 Swami et al used the Optum Research Database to study the rate of treatment intensification from 2014 to 2019 in 4,675 men with mCSPC.…”

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confidence: 99%

“…2 Since 2014, such treatment doublets have been incorporated into clinical practice and guidelines, yet real-world evidence suggests a low rate of adoption, owing amongst others to limited drug access, concerns about the safety of doublets in the typically elderly and often frail mCSPC patient, and the lack of validated predictive markers. 2 Swami et al used the Optum Research Database to study the rate of treatment intensification from 2014 to 2019 in 4,675 men with mCSPC. 3 Despite a slow increase over time, at the end of the study period only around one-third of patients overall received doublets.…”

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confidence: 99%

“…4,5 A steady increase in treatment intensification is welcome given that the next wave of even more intense therapy, ie, ADTDdocetaxelDARSi triplets, is at our doorstep. 2 Martin Smoragiewicz 1 and Urban Emmenegger 1…”

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Smoragiewicz

Emmenegger

2023

Journal of Urology

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Hematological Toxicity of PARP Inhibitors in Metastatic Prostate Cancer Patients with Mutations of BRCA or HRR Genes: A Systematic Review and Safety Meta-analysis

Maiorano,

De Giorgi,

Verzoni

et al. 2023

Targ Oncol

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Background PARP inhibitors (PARPis) are effective treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC) as single agents or in combination with androgen receptor-targeted agents (ARTA). However, a clinically relevant adverse effect of these agents is hematological toxicity, a typical class adverse event (AE), which can lead to treatment modifications and discontinuations. Objective We aimed to analyze the risk of hematological AEs, including anemia, neutropenia, and thrombocytopenia secondary to PARPi treatments in mCRPC. Patients and Methods This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. We systematically searched the PubMed, EMBASE, and Cochrane databases, the American Society of Clinical Oncology (ASCO), and the European Society of Medical Oncology (ESMO) meeting abstracts for clinical trials concerning the use of PARPis, both as single agents and in combination, in patients with mCRPC. The search deadline was 30 June, 2023. We analyzed the pooled incidence of all grades of and ≥ G3 anemia, neutropenia, and thrombocytopenia. We subsequently calculated risk ratios (RRs) for all grades of and ≥ G3 AEs of PARPis versus non-PARPis from randomized clinical trials (RCTs). Results Eleven phase 2/3 trials with olaparib, niraparib, rucaparib, and talazoparib administered as single agents or combined with ARTA were selected. Anemia was the most common all grades (38.6%) and ≥ G3 AE (24.9%). In the analysis of relative risk, six RCTs were included. The administration of PARPis significantly increased the risk of developing all grades of anemia (RR = 2.44), neutropenia (RR = 3.15), and thrombocytopenia (RR = 4.66) compared with non-PARPis. Similarly, a significant increase in the risk of ≥ G3 anemia (RR = 5.73) and thrombocytopenia (RR = 5.44), and a not significant increased risk of neutropenia (RR = 3.41), were detected. Conclusions In mCRPC, PARPis increase the risk of hematological toxicity compared with other treatments, both as single agents or combined with ARTA (high-quality evidence). Clinicians should be aware of this risk and the correct management, especially with the expected increased PARPis use in mCRPC. Supplementary Information The online version contains supplementary material available at 10.1007/s11523-023-01016-x.

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Combination treatment in metastatic prostate cancer: is the bar too high or have we fallen short?

Cited by 15 publications

References 63 publications

Far from the truth: Real‐world treatment patterns among newly diagnosed metastatic prostate cancer in the era of treatment intensification

Far from the truth: Real‐world treatment patterns among newly diagnosed metastatic prostate cancer in the era of treatment intensification

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Hematological Toxicity of PARP Inhibitors in Metastatic Prostate Cancer Patients with Mutations of BRCA or HRR Genes: A Systematic Review and Safety Meta-analysis

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