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    Home > Active Ingredient News > Urinary System > Talazoparib used in BRCA2 germline mutant mCRPC patients has an ORR of 50%!

    Talazoparib used in BRCA2 germline mutant mCRPC patients has an ORR of 50%!

    • Last Update: 2021-05-10
    • Source: Internet
    • Author: User
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    Founded in 1907, the AACR Association is the world's earliest and largest scientific organization dedicated to comprehensive, innovative and high-level cancer research.
    Many large-scale research results will be announced at the conference.

    The first week of this AACR annual meeting ended on April 15.

    During the meeting, TALAPRO-1 research published the final analysis results.

    Background: The TALAPRO-1 study included measurable lesions and disease progression assessed by RECIST1.
    1, and may be sensitive to PARP inhibitors (ATM, ATR, BRCA1, BRCA2, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, RAD51C) DNA damage response mutation (tDDRalt) in patients with metastatic castration-resistant prostate cancer (mCRPC).

    The enrolled patients had previously received at least one yew-based chemotherapy regimen and progressed after receiving at least one new endocrine therapy.

    The primary endpoint is the objective response rate (ORR).

    Method: Use FoundationOne® to detect tumor tissue, and use Ambry Custom Next-Cancer panel to detect saliva.

    Known/probably pathogenic tDDRalts are classified as germline mutations (also present in saliva) or somatic mutations (not present in saliva) or of unknown origin (ATR and FANCA mutations are not present in the germline Panel).

    The researchers assessed the heterozygosity of somatic mutation-germline mutations.

    Results: 128 patients were included in the study, and 127 patients received at least one dose of Talazoparib (safety population).

    Of 52 DDR-deficient patients assessed for germline and tumor DDR mutations, 27 (52%) had at least one tDDRalt germline mutation, 24 (46%) had somatic mutations, and 2 (4%) had mutations The source is unknown.

    The tDDRalt of one patient was derived from germline and somatic cells.

    The most common tDDRalts were BRCA (14 cases were germline mutations, 10 cases were somatic mutations) and ATM (4 cases were germline mutations, 7 cases were somatic mutations).

    The ORR of patients with germline mutations was 25%, the ORR of patients with BRCA2 germline mutations was 50%, and the ORR of patients with BRCA somatic mutations was 20% (P = 0.
    210).

    Overall, in the safety population (77 cases) for which heterozygosity can be assessed, 20.
    8% of patients had loss of heterozygosity (LOH) at tDDRalt, 22.
    1% of patients had heterozygosity, and 57.
    1% of patients had unknown heterozygosity.

    The ORR of heterozygous and LOH tDDRalt tumors were 43.
    8% and 11.
    8%, respectively (OR=5.
    83, P=0.
    057).

    Conclusion: This study showed that, among patients with mCRPC treated with multiple lines, germline mutations and/or heterozygous patients appear to be more responsive to Talazoparib treatment.

    Possible reasons include imbalance in gene specificity of the source of the mutation and sensitivity to TALA.

    A large sample size research is needed for further verification.

    Reference: CT027-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
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