Cabazitaxel activity in men with metastatic castration-resistant prostate cancer with and without DNA damage repair defects

Aldea, Mihaela; Lam, Laurent; Orillard, Émeline; Pérez, Casilda Llácer; Saint-Ghislain, Mathilde; Gravis, Gwénaëlle; Fléchon, Aude; Roubaud, Guilhem; Barthélémy, Philippe; Ricci, Francesco; Priou, Frank; Nevière, Zoé; Beaufils, Mathilde; Laguerre, Brigitte; Hardy, Anne-Claire; Hélissey, Carole; Ratta, Raffaele; Borchiellini, Delphine; Pobel, Cédric; Joly, Florence; Castro, Elena; Thiery‐Vuillemin, Antoine; Baciarello, Giulia; Fizazi, Karim

doi:10.1016/j.ejca.2021.09.029

Cited by 6 publications

(2 citation statements)

References 28 publications

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“…A post hoc analysis of the PROREPAIR-B study showed that the outcomes of patients with germline HHR mutations were worse than those of noncarriers following treatment with cabazitaxel [30]. Aldea et al [31] analysed the response to cabazitaxel in mCRPC patients with germline or somatic DDR defects and found no difference in response rates in patients with and without such alterations. However, the benefit for cabazitaxel was diminished in patients previously treated with PARPi.…”

Section: Key Pointsmentioning

confidence: 99%

Implications of DNA damage repair alterations for the management of prostate cancer

Lozano

Olmos

Castro

2022

Current Opinion in Urology

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Purpose of reviewIn this review, we summarize the prevalence of alterations in DNA damage repair (DDR) genes in prostate cancer, their clinical significance, the therapeutic strategies developed to take advantage of the impaired tumour ability to repair DNA and the diagnostic approaches available to identify patients likely to benefit from DDR-targeting agents.Recent findings DDR alterations are more frequent in metastatic than in localized prostate cancer and some of them associate with aggressive disease whereas the significance of others remain unclear. The most appropriate management approach for DDR-defective prostate cancer patients is unknown. Clinical trials have demonstrated the efficacy of different poly-ADP ribose polymerase inhibitors (PARPi) to treat metastatic castration-resistant prostate cancer patients with BRCA1/2 alterations, although there may be other DDR alterations that sensitize patients to these drugs. Multiple strategies to target DDR defects are being investigated, including PARPi in combination, platinum-based chemotherapy and immunotherapy, both in earlier and late disease stages. Optimization of molecular testing is paramount for the implementation of precision oncology in prostate cancer. SummaryCertain DDR defects present in prostate cancer have prognostic and therapeutic implications whereas the significance of other DDR alterations is yet to be elucidated.

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Section: Key Pointsmentioning

confidence: 99%

Implications of DNA damage repair alterations for the management of prostate cancer

Lozano

Olmos

Castro

2022

Current Opinion in Urology

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“…Patients with BRCA2 mutations seemed to demonstrate superior progression-free survival in the PROfound subgroup analysis [74], most likely because of the high rate of two hits or biallelic inactivation of BRCA2 versus ATM, RAD51C or other genes, which may not be as frequently biallelically inactivated. DNA repair mutations might also confer sensitivity to taxanes but results have been conflicting [80][81][82]. More research is needed to better understand the therapeutic implications of each individual DNA repair mutation and when PARP inhibitors versus taxanes are best indicated for mCRPC patients.…”

Section: Advanced Prostate Cancermentioning

confidence: 99%

The role of genetic testing in prostate cancer screening, diagnosis, and treatment

Calle

Bhanji²,

Pavlovich³

et al. 2022

Current Opinion in Oncology

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Purpose of reviewThis review provides an overview of the current role of genetic testing in prostate cancer screening, diagnosis, and treatment. Recent findingsRecent studies have uncovered few but highly penetrant rare pathogenic mutations (RPMs), in genes, such as BRCA2, with strong prostate cancer risk and outcomes associations. Over 260 single nucleotide polymorphisms (SNPs) have also been identified, each associated with small incremental prostate cancer risk and when combined in a polygenic risk score (PRS), they provide strong prostate cancer risk prediction but do not seem to predict outcomes. Tumor tissue sequencing can also help identify actionable somatic mutations in many patients with advanced prostate cancer and inform on their risk of harboring a germline pathogenic mutation. SummaryRPM testing, PRS testing, and tumor sequencing all have current and/or potential future roles in personalized prostate cancer care. Keywords genetic testing, germline mutations, polygenic risk score, prostate cancer MEASURES OF INHERITED PROSTATE CANCER RISK Family history and genetic ancestryRecording family history, self-reported race and ethnicity are some of the earliest forms of 'genetic' testing, and along with age remain some of the

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PARP Inhibition, a New Therapeutic Avenue in Patients with Prostate Cancer

Flippot

Patrikidou

Aldea

et al. 2022

Drugs

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Cabazitaxel activity in men with metastatic castration-resistant prostate cancer with and without DNA damage repair defects

Cited by 6 publications

References 28 publications

Implications of DNA damage repair alterations for the management of prostate cancer

Implications of DNA damage repair alterations for the management of prostate cancer

The role of genetic testing in prostate cancer screening, diagnosis, and treatment

PARP Inhibition, a New Therapeutic Avenue in Patients with Prostate Cancer

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