TEST:

BRACAnalysis CDx™

Olaparib has shown good results in patients with germline BRCA1/2 mutation-positive HER2-negative advanced/recurrent breast cancer who have a history of receiving anthracycline and taxane-based therapies. It was considered that even in recurrent breast cancer, the presence or absence of BRCA1/2 mutations should be actively sought even in advanced cases, and the administration of olaparib should be considered.

In clinical practice, 6.5% of patients treated with castration-resistant prostate cancer carried germline BRCA1/2 pathogenic variants. Japanese castration-resistant prostate cancer patients with germline BRCA1/2 mutants have a poor prognosis and may be less responsive to treatment with androgen receptor signaling inhibitors and taxane-based chemotherapy for castration-resistant prostate cancer.

"Myriad Genetics, Inc...and Personalis, Inc...announced a non-exclusive collaboration through which Myriad will market the Personalis®ImmunoID NeXT ultra-comprehensive biomarker discovery platform to its pharmaceutical partners who use the MyRisk® Hereditary Cancer Test, BRACAnalysis CDx® and/or MyChoice® CDx cancer tests."

The diagnosis of gBRCA PV-positive PC has increased revealed in recent years. These tumors appear to be sensitive to platinum-based chemotherapy, with long term survival observed in gATM PV + LPV-positive patients.

The rate of germline BRCA1 and BRCA2 mutations found in patients with unresectable pancreatic cancer was comparable to those of previous studies.An analysis of germline BRCA1 and BRCA2 mutations has benefits for all patients with unresectable pancreatic cancer with regard to decisions on therapeutic strategies in a clinical practice setting.

Multiple bone metastases appeared 5 months after the initiation of abiraterone therapy. Three courses of docetaxel and two courses of cabazitaxel were administered, but the disease progression continued...To our knowledge, no other cases of BRCA2 mutation positive IDC-P have been reported in Japan. After we started administration of Olaparib, the patient's PSA level was lowered and the disease progression stopped.

P1; Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

No abstracts available

P1; Trial completion date: May 2024 --> Dec 2024 | Trial primary completion date: May 2024 --> Dec 2024

"Myriad Genetics...announced multiple presentations of new data at the 2022 San Antonio Breast Cancer Symposium (SABCS), including a spotlight discussion on breast cancer risk prediction....Spotlight discussion highlights how combined risk score may lead to improved breast cancer prevention and screening strategies....Additionally, there will also be poster session (P6-01-24) about an independent EndoPredict study....The study looked at prospective long-term outcome data with EndoPredict for women with early-stage breast cancer."

"Myriad Genetics, Inc...announced the launch of UroSuite, a comprehensive suite of genetic risk assessment tests that cover every stage of prostate cancer care....UroSuite includes Myriad’s Prolaris® Prostate Cancer Test, MyRisk™ Hereditary Cancer Test, BRACAnalysis CDx^® and Precise™ Tumor Molecular Profile Test. The combination of tests provides integrated genetic insights and makes it easier to tailor therapy and clinical trial selection for patients....'Today’s launch of UroSuite reinforces Myriad Genetics’ commitment to advancing health and well-being for all through a set of testing solutions for prostate cancer care, best-in-class support, and access to genetics and cancer specialists,' said Paul J. Diaz, president and CEO, Myriad Genetics."

P1, N=28, Active, not recruiting, Pfizer | Trial completion date: Jul 2022 --> Aug 2024

"Myriad Genetics...announced Japan’s Ministry of Health, Labour and Welfare (MHLW) has granted expanded coverage for the use of Myriad’s BRACAnalysis Diagnostic System as a companion diagnostic to identify patients with germline BRCA-mutated (gBRCAm) and HER2-negative high-risk recurrent breast cancer who may benefit from Lynparza (olaparib)."

P2; Olaparib treatment demonstrated activity across all cohorts. The greatest efficacy was observed in the BRCAm cohorts, regardless of gBRCAm/sBRCAm. For patients without a BRCAm, greater efficacy was observed in the HRD-positive than the HRD-negative cohorts. The safety profile was consistent with that established in previous olaparib studies.

"This is the first report of the clinical outcome of PARP inhibitor and platinum-containing chemotherapy in a patient with a BRCA1 R1699Q variant. Despite BRCA1 mutation and high GIS, used as indicators of drug sensitivity, the recurrent tumor did not respond well to platinum agents and olaparib. BRCA1 R1699Q variant could differ from others in cancer risk and in drug response. Further studies are needed to confirm these observations."

P1; Trial completion date: Dec 2023 --> May 2024 | Trial primary completion date: Dec 2023 --> May 2024

In final OS analyses, maintenance olaparib capsules showed consistent clinical activity in BRCAm and sBRCAm PSROC pts. Exploratory analyses suggest similar activity in non-BRCA HRRm pts. No new safety signals were observed.

P1; Trial completion date: May 2023 --> Dec 2023 | Trial primary completion date: Nov 2022 --> Dec 2023

"Myriad Genetics...announced the U.S. Food and Drug Administration (FDA) has approved Myriad’s BRACAnalysis® CDx test for use as a companion diagnostic to identify patients with germline BRCA-mutated (gRBCAm) HER2 negative, high-risk early-stage breast cancer who may benefit from Lynparza (olaparib)....BRACAnalysis CDx is intended to detect and interpret germline BRCA1 and BRCA2 variants. The test identifies deleterious or suspected deleterious germline BRCA variants in patients with HER2 negative high-risk early breast cancer."

The genetic medicine for primary breast cancer patients with BRCA1/2 germline mutation is accelerating rapidly in Japan. Therefore, establishing a system for the genetic medicine would be urgent.

In these cases, the histological type, stage, subtype, BRCA mutation site, etc., were different from each other, and detailed support by genetic counseling was taken according to each medical condition such as surgery and postoperative adjuvant therapy.

P3; Very high concordance was demonstrated between tumor and germline BRCA testing, supporting wider implementation of tumor BRCA testing in ovarian cancer. Near 100% rates of bi-allelic loss of BRCA in platinum-sensitive relapsed ovarian tumors suggest routine testing for BRCA zygosity is not required in this population and reflects BRCA loss being a driver of tumorigenesis.

Moreover, salpingectomy alone is said to not decrease the risk of developing ovarian or breast cancer, so further discussion is evidently required. We discuss the current situation and problems in doing BRCA genetic test and RRSO in this review article.

In the final OS analysis, 18-mo OS ranged from 60–88% across the 4 cohorts . Consistent with the primary analysis, the 18-mo OS rate was highest in the BRCAm cohorts (similar OS in g and sBRCAm); among pts without a BRCAm, 18-mo OS was highest in the HRD +ve cohort . No new safety signals were observed compared with the primary analysis and with prior olaparib studies.

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 .

PFS in pts with PSROC who received maintenance olaparib was similar irrespective of s or g BRCAm status. Activity of maintenance olaparib was also shown in pts with a non-BRCA HRRm. PFS, HRQoL and tolerability were consistent with previous olaparib studies in this population.

P=N/A; Recruiting --> Completed

In patients with BRCA-mutated (BRCAm) tumors, olaparib monotherapy demonstrated a 70% reduction in the risk of disease progression or death compared to placebo and olaparib in combination with bevacizumab demonstrated a 67% reduction in the risk of disease progression or death compared to bevacizumab alone in homologous recombination deficient (HRD)-positive tumors. These approvals represent a major advance for the treatment of women with advanced ovarian cancer who are in complete or partial response following their initial platinum-based chemotherapy.

P=N/A; Not yet recruiting --> Recruiting

P2 | "Olaparib treatment demonstrated activity across all cohorts. As observed in the maintenance setting, similar efficacy was seen in the gBRCAm and sBRCAm cohorts. For non-BRCAm pts, longer median PFS and higher ORR were observed in the HRD+ve cohort."

P; N=200; Not yet recruiting; Sponsor:AstraZeneca