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    7ms
    Late Onset Familial Medullary Thyroid Cancer Arising from a Germline RET Polymorphism: The Need for Germline Screening and an Individualized Approach (ENDO 2024)
    Sporadic MTC is typically diagnosed in patients during the 4th and 6th decades of life and is attributed to somatic mutations within tumor cells. It is not apparent what proportion of patients with clinically apparent sporadic MTC have an unsuspected germline mutation in the RET gene conferring heritable disease. This case highlights the importance of screening all patients with MTC for germline RET mutations so family members can be appropriately referred for testing.
    Clinical
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    RET (Ret Proto-Oncogene)
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    RET mutation
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    CustomNext-Cancer®
    over1year
    Exploration of germline (g) vs somatic (s) origin of homologous recombination repair (HRR) gene alterations and potential associations with antitumor activity in the HRR-deficient population from TALAPRO-2 (ESMO 2023)
    Background TALAPRO-2 evaluated the PARP inhibitor talazoparib (TALA) combined with the androgen receptor pathway inhibitor enzalutamide (ENZA) as 1st-line treatment in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). Though the analyses were exploratory, a shorter rPFS in PBO + ENZA-treated gHRRm pts may reflect an intrinsically poor prognosis subgroup that could be prioritized for TALA + ENZA treatment. Further study is warranted.
    Clinical • PARP Biomarker • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))
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    CustomNext-Cancer®
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    Talzenna (talazoparib) • Xtandi (enzalutamide capsule)
    over2years
    Prevalence of DNA damage repair (DDR) alterations in patients with metastatic hormone-sensitive prostate cancer (mHSPC) receiving enzalutamide (ENZA) or placebo (PBO) plus androgen deprivation therapy (ADT): ARCHES post hoc analysis. (ASCO 2022)
    This post hoc analysis found a lower prevalence of DDR alterations in patients with mHSPC in ARCHES, compared with the 7–12% previously reported in patients with metastatic castration-resistant prostate cancer (Lozano et al. Br J Cancer 2021; Pritchard et al. N Engl J Med 2016).
    Retrospective data • Clinical
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    CustomNext-Cancer®
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    Xtandi (enzalutamide capsule)
    almost3years
    TALAPRO-1: Talazoparib monotherapy in metastatic castration-resistant prostate cancer (mCRPC) with tumor DNA damage response alterations (DDRm)—Exploration of germline DDR alteration landscape and potential associations with antitumor activity. (ASCO-GU 2022)
    Here we report a 20% incidence of gHRRm for this population of men with mCRPC preselected based on tumor HRRm status, which may be impacted by low Ns and assay specific differences in variant calling. In this population, no association with differential antitumor activity was observed with gHRRm status as assessed using germline results alone, or assessed holistically using a combination of tumor and saliva results and SGZ prediction.
    PARP Biomarker • BRCA Biomarker
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    BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C)
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    FoundationOne® CDx • CustomNext-Cancer®
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    Talzenna (talazoparib)
    over3years
    [VIRTUAL] Neoadjuvant talazoparib (TALA) in patients (pts) with germline BRCA1/2 (gBRCA1/2) mutation-positive, early HER2-negative breast cancer (BC): Exploration of tumor BRCA mutational status and zygosity and overall mutational landscape in a phase 2 study. (ASCO 2021)
    Tumor BRCA mutations were evident in nearly all pts in the biomarker analysis population, with BRCA LOH evident in all but 1 BRCA-mutated tumor . No pts had non-BRCA germline DDR gene mutations; tumor TP53 mutations were near-universal . MYC and RAD21 each exhibited CNAs in 27% of tumors, with no association with pCR .
    P2 data • Clinical • PARP Biomarker • BRCA Biomarker
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    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset) • RAD21 (RAD21 Cohesin Complex Component)
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    TP53 mutation • BRCA2 mutation • BRCA1 mutation • HER-2 negative • BRCA1 mutation + BRCA2 mutation • BRCA mutation
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    FoundationOne® CDx • BRACAnalysis CDx™ • CustomNext-Cancer®
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    Talzenna (talazoparib)
    over3years
    [VIRTUAL] TALAPRO-1 final data: Talazoparib (TALA) monotherapy in men with DNA damage response alterations (DDRalt) and metastatic castration-resistant prostate cancer (mCRPC): Exploration of DDRalt germline/somatic origin and zygosity (AACR 2021)
    In this heavily pretreated mCRPC population, based on this retrospective ad hoc exploratory subgroup analysis, pts with germline and/or homozygous tDDRalt appeared to be numerically most likely to respond to TALA. Potential reasons include gene-specific imbalances in origin/zygosity of alterations and/or sensitivity to TALA. Further investigation in larger data sets is warranted.
    PARP Biomarker • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))
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    DDR mutation
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    CustomNext-Cancer®
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    Talzenna (talazoparib)
    over4years
    [VIRTUAL] TALAPRO-1: Talazoparib (TALA) monotherapy in men with DNA damage response alterations (DDRalt) and metastatic castration-resistant prostate cancer (mCRPC): Exploration of DDRalt germline/somatic origin (ESMO 2020)
    Funding: Pfizer. Clinical trial identification: NCT03148795.
    PARP Biomarker • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • ATR (Ataxia telangiectasia and Rad3-related protein) • RAD51C (RAD51 paralog C) • MRE11A (MRE11 homolog, double strand break repair nuclease)
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    FoundationOne® CDx • CustomNext-Cancer®
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    Talzenna (talazoparib)