Professor Yao Shuzhong: First-line maintenance of PARP inhibitors to maintain therapy biomarkers from BRCA to HRD plus, HRD Score testing helps screening of people benefiting from ovarian cancer

With the progress of PARP inhibitor research, thethe path ofof ovarian cancer is expandingEspecially in the first-line maintenance treatment approved by theFDA, from Olapa's use of BRCA mutation population, to Olapari-Bevalzumab for HRD-positive populations, achieved a breakthrough in the first-line maintenance treatment beneficiaries of PARP inhibitors from BRCA to HRD-plus populationsNirapali's first-line maintenance therapy, while approved for the entire population, is still better benefited from BRCA plus HRD plusClinical research advances related to PARP inhibitors have also contributed to the updating and development of guidelines at home and abroad, such as the NCCN Clinical Practice Guidelines for Ovarian Cancer in the United States and the Clinical Application Guidelines for Ovarian Cancer PARP Inhibitors of the Chinese Medical Association's Gynaecological Oncology Branch, which have made new recommendations for the first-line maintenance of ovarian cancerThe value of HRD testing is emphasized in the recommendations of first-line maintenance therapy2020 edition of the NCCN Ovarian Cancer Clinical Practice Guide, the first line of maintenance treatment update, recommended BRCA wild patients reference HRD status guidance medication
the first choice of treatment of ovarian cancer is surgery, or new auxiliary chemotherapy after surgery, after obtaining satisfactory tumor cell reduction surgery, and then to the patient after postoperative chemotherapyOvarian cancer patients are generally sensitive to chemotherapy, after which complete or partial remission can be achieved, i.eCR or PRIn the past, in this case, we stopped intervening with patients, but re-treated after relapse, but treatment after relapse becomes more and more difficultIn recent years, as research into the treatment of ovarian cancer has continued, it has been found that the use of drugs to intervene can prolong the patient's progression-free survival (PFS) from CR or PR after initial treatment to relapse of symptoms In the SOLO1 study, patients with BRCA mutationreceiving received olapari first-line maintenance therapy, which significantly delayed relapse compared to placebos, and in the PRIMA study of , the first-line maintenance therapy in Nirapari extended PFS in all population patients, but the brcA plus and HRD plus populations benefited more significantly PAOLA-1 study published at the 2019 ESMO Conference showed that the use of olapari in combination belaval smoofes for first-line maintenance therapy can significantly benefit BRCA plus and HRD-plus populations based on the data from the above study, the 2020 NCCN Clinical Practice Guidelines for Ovarian Cancer have been updated in the first-line maintenance treatment section, and parP inhibitors have become standard treatment options for first-line maintenance therapy based on the BRCA mutation status and the use of bebarazumab in first-line treatment Specifically: initial treatment did not receive belaval stomp: BRCA1/2 wild type or unknown, recommended nirapali (class 2A) maintenance therapy; initial treatment received treatment with belaval beads monotomatic: BRCA1/2 wild or unknown, recommended belaval beads monotomatodsis , or belapalitavirus (class 2A) maintenance therapy; it is worth noting that the applicable population for maintenance therapy in ncCN guidelines is patients with stage II to IV, patients with stage I are not recommended, and phase II evidence is limited It is only available to patients who obtain CR or PR after initial treatment In the new NCCN guidelines, although first-line maintenance medications are recommended for BRCA mutation status, it is also stated in footnotes that "for non-BRCA mutation patients, HRD status may provide reference information on the benefits of PARP inhibitor treatment." "
and NCCN guidelines, the domestic guidelines to include HRD status in the ovarian cancer first-line maintenance treatment choices of stratification factors
the Chinese Medical Association Gynaecological Oncology Branch of the "Clinical Application Of Ovarian Cancer PARP Inhibitors Guidelines" also recommend parP inhibitors for first-line maintenance treatment Unlike NCCN guidelines, which recommend first-line maintenance treatment based on the presence of no use of belavzumab and BRCA mutation states in initial treatment, the Chinese Medical Association's guidelines also consider HRD status as a further stratification factor, in addition to considering BRCA mutation status and the use of first-line belaval beads The recommended drug is essentially the same as the NCCN guidelines, but the recommended level is slightly different no use of belavzumab in initial chemotherapy BRCA wild type/HRD positive: based on data of 0.5 for the BRCA wild/HRD-positive subgroup of BRCA wild type/HRD-positive subgroup, which was recommended as a category 1 The NCCN guidelines recommendnirapali in BRCA wild patients as a Class 2A based on data from the PAOLA-1 study, the domestic guidelines add Olapari (Class 2B) recommendations, while NCCN guidelines do not used belava zuma singums BRCA wild type/HRD positive in initial chemotherapy: based on the data of 0.43 data of olapari-Bervalsssingpf-bifare sepsis in the PAOLA-1 study The recommended class of olapari-belaval bead suplavitum in BRCA wild patients in ncCN guidelines is Class 2A The PRIMA study did not include whether the initial treatment had used belaval sebutax as a stratification factor in the group, and given the benefits of Nirapali in BRCA wild and HRD-positive patients, the domestic guidelines recommended nirapali as a category 2A for BRCA wild/HRD-positive patients BRCA Wild/HRD Negative: Domestic Guidelines do not recommend Olapari-Bevalzumab Since the NCCN guidelines do not stratify HRD, the BRCA wild type is recommended for Olapari and Beval-Bead monotoidal (Class 2A) BRCA wild/HRD negative, the domestic guide to Nirapali as a Class 2B recommendation, NCCN guidelines do not make recommendations HRD testing makes PARP inhibitors first-line maintenance therapy recommend more accurate , the beneficiary population more ovarian cancer first-line maintenance treatment options if based on the BRCA gene mutation state, then patients without BRCA mutation targeted treatment options are quite limited Because of ovarian cancer diagnosed only 25% have BRCA mutations, of which 15% are germ BRCA mutations The proportion of HRD-positive in the overall ovarian cancer population was as high as 50%, including BRCA mutations, BRCA1 and RAD51 promoter methylation, BRIP1 and other mutations, in other words, half of hrD-positive patients were BRCA wild Based on the results of the PRIMA study and the PAOLA-1 study, in addition to patients with BRCA mutations, PATIENTs with BRCA wild but HRD-positive had significant benefits from PARP inhibitors The first-line maintenance treatment approved by the FDA before fda approval is olapari for patients with BRCA mutations, and last month, nirapali was approved for use in whole population patients, olapari-bevalo zuma supaina for HRD-positive patients The approval of HRD status in FDA first-line maintenance treatment and the recommendation of domestic and foreign guidelines are of great practical significance for the first-line maintenance treatment of ovarian cancer On the one hand, HRD testing further broadens the beneficiary population of PARP inhibitors, and on the other hand, HRD, combined with BRCA mutation status, can be more targeted for first-line maintenance treatment recommendations, such as: BRCA wild type/HRD-positive patients, olapari-bevalzumab or Olapari or Nirapari can be recommended Patients with BRCA wild/HRD negative can only recommend Nirapali, not Olapari hence the need for HRD testing, which is of guiding value in our selection of different types of drugs develop hrD score model based on Chinese groups to provide Chinese patients with more suitable screening testing for people benefiting from PARP inhibitors
the successful development and marketing of a drug, depending on the development of biomarkers Regarding HRD testing, the representative product that has been approved abroad is myChoice, myChoice participated in the famous NOVA trial, initiated the first large-scale clinical validation in ovarian cancer, and explored the significance of HRD score in the maintenance therapy in patients with platinum-sensitive recurrence using PARP inhibitors Although the final approval was for platinum-sensitive populations, HRD score did distinguish between different populations, i.e BRCA mutations benefited the most, HRD positive scored, and HRD negative severned Later myChoice experienced quadRA research, PAOLA-1 and PRIMA studies, which were well clinically validated for Chinese patients, if domestic enterprises can develop similar products, has a very important clinical practical significance, on the one hand can be easy to use, on the other hand, there is a price advantage, so that more patients are tested It is worth noting that HRD score scored through genomic instability is based on the genome-wide single nucleotide polymorphism (SNP) site fraction to output the scores of the three markers, while the distribution of the SNP is someone's difference, the domestic urgent need to develop Chinese its own HRD Score model in China, The following two points of Reference Technology HRD detection product development have achieved: based on the genetic background development of Chinese groups, can well cover the Chinese group of high polymorphic site SNP comprehensive detection of LOH, TAI and LST genome scar markers, better layered Chinese group HRD state , a randomized, dual-blind, placebo-controlled, multicenter-center Phase III clinical study of domesticPARP inhibitors, jointly initiated by Priebus and clinical experts, was designed to explore parP inhibitors or combined drug contrasts with placebos for post-platinum chemotherapy for advanced ovarian cancer The clinical trial used The HRD score test of Prebenchmark Technology to study the effect of HRD status on the efficacy of PARP inhibitors domestic HRD detection products based on Chinese group background development, Pribenchmark Technology developed in the HRD model algorithm, as well as the participation of the core team of TCGA, the output of the raw letter algorithm is more accurate We look forward to using this clinical trial application to provide more validation data for hrD testing in China, and to provide Chinese patients with more suitable screening testing for people benefiting from PARP inhibitors Source: Cancer Information