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Impact of DNA damage repair defects and aggressive variant features on response to carboplatin-based chemotherapy in metastatic castration-resistant prostate cancer.


ABSTRACT: Platinum-based chemotherapy is not standard of care for unselected or genetically selected metastatic castration-resistant prostate cancer (mCRPC) patients. A retrospective assessment of 71 patients was performed on platinum use in the Netherlands. Genetically unselected patients yielded low response rates. For a predefined subanalysis of all patients with comprehensive next-generation sequencing, 30 patients were grouped based on the presence of pathogenic aberrations in genes associated with DNA damage repair (DDR) or aggressive variant prostate cancer (AVPC). Fourteen patients (47%) were DDR deficient (DDRd), of which seven with inactivated BRCA2 (BRCA2mut). Six patients classified as AVPC. DDRd patients showed beneficial biochemical response to carboplatin, largely driven by all BRCA2mut patients having >50% prostate-specific antigen (PSA) decline and objective radiographic response. In the wild-type BRCA2 subgroup, 35% had a >50% PSA decline (P = .006) and 16% radiographic response (P?

SUBMITTER: Slootbeek PHJ 

PROVIDER: S-EPMC7756382 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Impact of DNA damage repair defects and aggressive variant features on response to carboplatin-based chemotherapy in metastatic castration-resistant prostate cancer.

Slootbeek Peter H J PHJ   Duizer Marleen L ML   van der Doelen Maarten J MJ   Kloots Iris S H ISH   Kuppen Malou C P MCP   Westgeest Hans M HM   Uyl-de Groot Carin A CA   Pamidimarri Naga Samhita S   Ligtenberg Marjolijn J L MJL   van Oort Inge M IM   Gerritsen Winald R WR   Schalken Jack A JA   Kroeze Leonie I LI   Bloemendal Haiko J HJ   Mehra Niven N  

International journal of cancer 20201003 2


Platinum-based chemotherapy is not standard of care for unselected or genetically selected metastatic castration-resistant prostate cancer (mCRPC) patients. A retrospective assessment of 71 patients was performed on platinum use in the Netherlands. Genetically unselected patients yielded low response rates. For a predefined subanalysis of all patients with comprehensive next-generation sequencing, 30 patients were grouped based on the presence of pathogenic aberrations in genes associated with D  ...[more]

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