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    Home > Medical News > Latest Medical News > About the study of the benefits of PARP inhibitors in OS in advanced breast cancer

    About the study of the benefits of PARP inhibitors in OS in advanced breast cancer

    • Last Update: 2021-02-01
    • Source: Internet
    • Author: User
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    As an example of precise treatment of potential genetic causes of cancer, the development of polyADP cypolycolymer (PARP) inhibitors spans a wide range of cancer types, most notably ovarian and breast cancer patients with BRCA mutations, and has shown therapeutic potential for other cancers as well as non-tumor diseases.
    1. PFS and OS results of phase III trials evaluating PARP inhibitors in different cancer types of BRCA1/2 mutations About 5% of breast cancer patients were associated with BRCA1/2 gene embryo line mutations (BRCA1 gene 3%, BRCA2 Genes 2%) and BRCA1 mutations lead to mostly triple-negative breast cancer (70%), while BRCA2 mutations are more likely to lead to estrogen-positive breast cancer (70%), and the mutation is more likely to occur in patients with a family history of breast cancer, young and triple-negative breast cancer.
    January 2018, the FDA approved Olapali as the first PARP inhibitor to treat patients with BRCA1/2 mutation, HER2-negative advanced breast cancer (ABC).
    year, two other Phase III studies evaluating the efficacy of PARP inhibitors in patients with BRCA1/2 mutant advanced breast cancer have opened up new treatment options, but there are still some outstanding issues.
    : OlympioD study Olaparib's approval is based on Data from Phase III study OlympiAD.
    in the study, women with BRCA1/2 mutations in the reproductive line were randomly assigned chemotherapy drugs (Eliblin, Carpentabine, or Changchun Ruibin) chosen by Olapali or a doctor.
    the trial included advanced patients who had previously received ≤2-line chemotherapy (including new assisted, assisted chemotherapy), previously received cyclocycline and yew, and had been estrogen-positive (ER-plus), and ≥1-line endocrine therapy.
    excluded (new) patients who developed the disease within 12 months of (new) complementary platinum drug therapy or during platinum drug therapy.
    : NextMed database results show that Olapali's total remission rate (ORR), medium progression-free lifetime (PFS), and toxicity characteristics are all better than chemotherapy.
    significant difference in total lifetime (OS) was not confirmed in the intent therapy (ITT) population, but the results were favorable to Olapali.
    , however, pre-planned strated subgroup analysis showed that patients receiving olapali as a first-line treatment benefited from OS for 22.6 months, while the chemotherapy group benefited for 14.7 months (HR 0.51, 95% CI 0.29-0.90).
    notable, 29 percent of patients in the Olapali and 42 percent of the chemotherapy group received follow-up platinum therapy, and 0.5 percent and 8 percent received follow-up PARP inhibitors, respectively.
    tarazapani: EMBRACA Research EMBRACA Research is an open, randomized, global Phase III study designed to compare the efficacy and safety of the PARP inhibitor Talazoparib and single-drug chemotherapy (Capatabin, Erebrin, Gisitalabin, or Changchun Ruibin) for the treatment of local late stage or metastasis HER2-negative breast cancer with BRCA1/2 mutations in the embryo line.
    based on this study, he became the second PARP inhibitor to be approved by regulators for advanced breast cancer.
    the trial included ABC patients who had previously received ≤3-line chemotherapy (including new assisted, assisted chemotherapy) and cyclocycline and/or yew alkanes.
    excluded patients who developed the disease within 6 months of (new) complementary platinum drug therapy or during platinum drug therapy.
    source: NextMed database results show that he has twice as much ORR and better PFS than chemotherapy.
    recently updated OS analysis shows that the middle OS of the ITT population has not benefited.
    It is worth noting that in his lazopani group, 46 per cent of patients continued to receive follow-up platinum medications and 4.5 per cent continued to receive PARP inhibitors, compared with 42 per cent and 33 per cent in the control group, respectively.
    similar toxic characteristics to his lazopani, mainly hematological toxicity, nausea and fatigue.
    in two studies, Olympioad and EMBRACA, the quality of life (QOL) of the PARP inhibitor treatment group was better than that of chemotherapy, with a delay in the time to disease deterioration.
    : The BROCADE3 study, recently published in The Lancet Oncology, was the first Phase III study to evaluate the platinum-containing co-PARP inhibitor Vilipani in ABC patients with BRCA1/2 mutations in the embryo line.
    the trial included ABC patients who had previously received ≤2-line chemotherapy (including new assisted, assisted chemotherapy) and ≤1-line platinum drugs and had no disease progressation during or within 12 months of treatment.
    patients were randomly assigned to receive a joint or non-combined Velipani treatment with yew alcohol and carpone.
    who stop chemotherapy before the disease progresses can continue to receive a single dose of Vilipani or a placebo.
    control group were treated with the open-label Velipani monotherapy after the disease progressed.
    : NextMed Database Study shows that the Vilipani group significantly extended the mid-PFS (14.5 months vs 12.6 months; HR 0.71; P=0.0016) compared to the control group.
    effects persist, with 2-year PFS at 33.6% vs 19.8% and 3-year PFS at 25.7% vs 10.7%.
    safety, the occurrence and severity of adverse events increased significantly, especially hematological toxicity.
    41% of patients in the Vilipani group and 34% in the control group were discontinued before the disease progressed due to adverse events and then received blind monotherapy.
    , 44 percent of patients in the control group received follow-up Vilipani treatment.
    most common time for conversion to blind monotherapy is after 6 cycles of combined chemotherapy.
    the neutral OS data supports Vilipani numerically, but is not statistically significant.
    QOL in the Wilipani group did not improve compared to the placebo group.
    it real or not? These three studies have undoubtedly opened up a "place" for PARP inhibition in the application of BRCA1/2 defect ABC therapy;
    a major criticism that neither of the studies set OS as a common primary endpoint, greatly limiting the likelihood of detecting OS benefits. table
    : CLINICAL trials of PARP inhibitors in ABC patients with BRCA1/2 mutations in the reproductive system (Source: Nat Rev Clin Oncol) In addition, the patients in these study groups, especially those involved in single-drug therapy, were heterogeneous in terms of the number of previous treatment lines and could dilute any OS benefit.
    in three studies, more than 40 percent of patients continued to receive follow-up PARP inhibitors or platinum drugs.
    the late separation of the PFS curve between the Wilipani group and the control group in the BROCADE3 study (source: lancet oncol) must also be careful in explaining the late separation of the PFS curve in the BROCADE3 study, for two key reasons.
    , a significant proportion of patients who stopped combined chemotherapy and did not progress continue to receive blind monotherapy, therefore, Vilipani monotherapy may drive curve separation.
    , 2 and 3 years PFS is not an empirical substitute for breast cancer OS benefits.
    The cross-comparison of PFS between single-drug therapy studies and BROCADE3 is particularly cautious, taking into account the higher proportion of subjects who have previously received excessive line therapy in single-drug treatment studies and the differences in the proportion of patients previously exposed to platinum

    Finally, when incorporating these studies into background analysis, it is important to emphasize that in EMBRACA and OlympioAD studies, the clinical efficacy and quality of life of PARP inhibitors are slightly better than that of standard chemotherapy, which is particularly important in treating patients with triple negative breast cancer (TNBC), even without OS benefits.
    in the late stages of incurability, the balance of quality of life and survival time is critical, and the main goal of treatment is to improve QOL without reducing efficacy.
    Conclusion Currently, PARP inhibitors appear to be the first-line treatment of choice for people with BRCA1/2 mutations in the reproductive system, while there is still much debate about how PD-L1-positive people choose between immunosupamine inhibitors (ICIs) and PARP inhibitors.
    for patients with advanced breast cancer with ER plus, HER2, the preferred first-line treatment is a combined CDK4/6 inhibitor for endocrine therapy, independent of the BRCA1/2 state.
    there are still many outstanding issues in the future, such as the application value of PARP inhibitors compared to platinum monotherapy in BRCA1/2 mutation ABC patients.
    With the widespread use of CDK4/6 inhibitors in ER-plus, HER2-advanced breast cancer, and ICIs in PD-L1-TNBC, head-to-head comparisons in the first-line background will be difficult to implement, but can be further explored as a second-line treatment option.
    addition, further follow-up of these queues is necessary to understand the potential resistance of chemotherapy after exposure to PARP inhibitors and the cross-resistance between PARP inhibitors and platinum drugs.
    : 1 s Paluch-Shimon S, Cardoso F. PARPors come of age. Nat Rev Clin Oncol. 2020 Nov 25. 2# Grinda T, Delaloge S. Survival benefits of PARP inhibitors in advanced breast cancer: a mirage? Ann Oncol. 2020 Nov; 31(11):1432-1434.
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