Olaparib tolerability and common adverse-event management in patients with metastatic castration-resistant prostate cancer: Further analyses from the PROfound study

Roubaud, Guilhem; Özgüroǧlu, Mustafa; Penel, Nicolas; Matsubara, Nobuaki; Mehra, Niven; Kolinsky, Michael; Procopio, Giuseppe; Feyerabend, Susan; Joung, Jae Young; Gravis, Gwénaëlle; Nishimura, Kazuo; Gedye, Craig; Padua, Charles; Shore, Neal D.; Thiery‐Vuillemin, Antoine; Saad, Fred; Alphen, Robbert van; Carducci, Michael A.; Desai, Chintu; Brickel, Neil; Poehlein, Christian; Rosario, Paula del; Fizazi, Karim

doi:10.1016/j.ejca.2022.04.016

Cited by 12 publications

(3 citation statements)

References 27 publications

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“…Common adverse events reported with PARPi treatments include anemia and nausea. The incidence of anemia as an adverse event was similar across clinical trials of each PARPi, excluding veliparib (all-grade anemia: 46.0-65.8% and grade ≥ 3: 15.1-46.5%); however, the rate of anemia incidence was higher for talazoparib than for the others [288,[291][292][293][294][295][296]298]. The rate of anemia incidence (all-grade and grade ≥ 3 anemia) due to veliparib was the lowest; however, an important consideration is that this trial had a small sample size (n = 74) [288].…”

Section: Parp Inhibitors (Parpis) For Mcrpc With Alterations In Hrr G...mentioning

confidence: 88%

Molecular Mechanisms of Prostate Cancer Development in the Precision Medicine Era: A Comprehensive Review

Maekawa,

Takata,

Obara

2024

Cancers

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The progression of prostate cancer (PCa) relies on the activation of the androgen receptor (AR) by androgens. Despite efforts to block this pathway through androgen deprivation therapy, resistance can occur through several mechanisms, including the abnormal activation of AR, resulting in castration-resistant PCa following the introduction of treatment. Mutations, amplifications, and splicing variants in AR-related genes have garnered attention in this regard. Furthermore, recent large-scale next-generation sequencing analysis has revealed the critical roles of AR and AR-related genes, as well as the DNA repair, PI3K, and cell cycle pathways, in the onset and progression of PCa. Moreover, research on epigenomics and microRNA has increasingly become popular; however, it has not translated into the development of effective therapeutic strategies. Additionally, treatments targeting homologous recombination repair mutations and the PI3K/Akt pathway have been developed and are increasingly accessible, and multiple clinical trials have investigated the efficacy of immune checkpoint inhibitors. In this comprehensive review, we outline the status of PCa research in genomics and briefly explore potential future developments in the field of epigenetic modifications and microRNAs.

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Section: Parp Inhibitors (Parpis) For Mcrpc With Alterations In Hrr G...mentioning

confidence: 88%

Molecular Mechanisms of Prostate Cancer Development in the Precision Medicine Era: A Comprehensive Review

Maekawa,

Takata,

Obara

2024

Cancers

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“…No novel safety signals were observed besides those included in the product information. 18 , 19 We had one patient with a rare allergy to olaparib leading to discontinuation of the treatment, although desensitization and subsequent continuation of olaparib would be possible. 13 …”

Section: Discussionmentioning

confidence: 99%

Efficacy of olaparib in advanced cancers with germline or somatic mutations in BRCA1, BRCA2, CHEK2 and ATM, a Belgian Precision tumor-agnostic phase II study

Joris,

Denys,

Collignon

et al. 2023

ESMO Open

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“…Recently, the success of PARP inhibitors in other solid tumors has sparked interest in their potential application in mCRPC treatment, leading to multiple RCTs comparing PARP inhibitors with SOC treatment [6][7][8][9]. As mutations of homologous recombination repair (HRR) genes (e.g., BRCA1/2) are found in approximately one-quarter of cases of mCRPC, multiple randomized clinical trials have been conducted to explore the efficacy and safety of PARP inhibitors compared to SOC treatments [10][11][12][13][14][15][16][17][18][19][20][21][22]. Notably, due to the relatively better survival benefits observed in patients with BRCA1/2/ATM alterations in the treatment arm of the PROfound trial, olaparib has been approved and recommended for those with HRR gene alterations who have progressed to mCRPC after receiving previous next-generation hormonal drug treatment [13].…”

Section: Introductionmentioning

confidence: 99%

Poly (ADP-ribose) Polymerase Inhibitors in Patients with Metastatic Castration-Resistant Prostate Cancer: A Meta-Analysis of Randomized Controlled Trials

Chao,

Wang,

et al. 2023

Medicina

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Context: Several recent randomized controlled trials (RCTs) have reported on the survival benefits of poly (ADP-ribose) polymerase inhibitors (PARPi) compared to standard-of-care (SOC) treatment (enzalutamide, abiraterone, or docetaxel) in patients with metastatic castration-resistant prostate cancer (mCRPC). However, there is a limited integrated analysis of high-quality evidence comparing the efficacy and safety of PARPi and SOC treatments in this context. Objective: This study aims to comprehensively analyze the survival benefits and adverse events associated with PARPi and SOC treatments through a head-to-head meta-analysis in mCRPC. Evidence acquisition: A systematic review search was conducted in PubMed, Embase, Clinical trials, and the Central Cochrane Registry in July 2023. RCTs were assessed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The systematic review was prospectively registered on PROSPERO (CRD42023441034). Evidence synthesis: A total of 8 studies, encompassing 2341 cases in the PARPi treatment arm and 1810 cases in the controlled arm, were included in the qualitative synthesis. The hazard ratio (HR) for radiographic progression-free survival (rPFS) and overall survival (OS) were 0.74 (95% CI, 0.61–0.90) and 0.89 (95% CI, 0.80–0.99), respectively, in the intention-to-treatment patients. For subgroup analysis, HRs for rPFS and OS in the BRCA-mutated subgroup were 0.39 (95% CI, 0.28–0.55) and 0.62 (95% CI, 0.38–0.99), while in the HRR-mutated subgroup, HR for rPFS was 0.57 (95% CI, 0.48–0.69) and for OS was 0.77 (95% CI, 0.64–0.93). The odds ratio (OR) for all grades of adverse events (AEs) and AEs with severity of at least grade 3 were 3.86 (95% CI, 2.53–5.90) and 2.30 (95% CI, 1.63–3.26), respectively. Conclusions: PARP inhibitors demonstrate greater effectiveness than SOC treatments in HRR/BRCA-positive patients with mCRPC. Further research is required to explore ways to reduce adverse event rates and investigate the efficacy of HRR/BRCA-negative patients.

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Olaparib tolerability and common adverse-event management in patients with metastatic castration-resistant prostate cancer: Further analyses from the PROfound study

Cited by 12 publications

References 27 publications

Molecular Mechanisms of Prostate Cancer Development in the Precision Medicine Era: A Comprehensive Review

Molecular Mechanisms of Prostate Cancer Development in the Precision Medicine Era: A Comprehensive Review

Efficacy of olaparib in advanced cancers with germline or somatic mutations in BRCA1, BRCA2, CHEK2 and ATM, a Belgian Precision tumor-agnostic phase II study

Poly (ADP-ribose) Polymerase Inhibitors in Patients with Metastatic Castration-Resistant Prostate Cancer: A Meta-Analysis of Randomized Controlled Trials

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