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Association details:
| Biomarker: | BRCA2 mutation |
|---|---|
| Cancer: | Breast Cancer |
| Drug: | Lynparza (olaparib) (PARP inhibitor) |
| Direction: | Sensitive |
Evidence:
Source:
Title:
Management of Hereditary Breast Cancer: American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Guideline
Published date:
04/03/2020
Excerpt:
Recommendations...Poly (ADP-ribose) polymerase (PARP) inhibitors (olaparib and talazoparib) are preferable to nonplatinum single-agent chemotherapy for treatment of advanced BC in BRCA1/2 carriers.
Secondary therapy:
Chemotherapy
DOI:
10.1200/JCO.20.00299
Source:
Excerpt:
While olaparib and talazoparib are FDA indicated in HER2-negative disease, the panel supports use in any breast cancer subtype associated with a germline BRCA1 or BRCA2 mutation.
Source:
Title:
VP1-2022: Pre-specified event driven analysis of Overall Survival (OS) in the OlympiA phase III trial of adjuvant olaparib (OL) in germline BRCA1/2 mutation (gBRCAm) associated breast cancer
Published date:
04/01/2022
Excerpt:
IDFS and DDFS were sustained with similar effect size: IDFS HR 0.63 (95% CI 0.50, 0.78), 4-yr IDFS 82.7% vs 75.4% (diff. 7.3%; 95% CI 3.0%, 11.5%). DDFS HR 0.61; 95% CI 0.48, 0.77); 4-yr DDFS 86.5% vs 79.1% (diff. 7.4%; 95% CI 3.6%, 11.3%)….In pts with gBRCAm and high-risk HER2-negative EBC after [N]ACT, at 3.5 years MFU, adjuvant olaparib significantly improved OS, as well as IDFS and DDFS...
DOI:
https://doi.org/10.1016/j.annonc.2022.03.008
Source:
Title:
4355 - Analysis of BRCA genes and homologous recombination deficiency (HRD) scores in tumours from patients (pts) with metastatic breast cancer (mBC) in the OlympiAD trial
Published date:
09/30/2019
Excerpt:
In olaparib (ola) pts with a BRCAm, ORR was 60% (6/10) and 57% (37/65) in pts with HRD score <42 and ≥42, respectively...BRCA2; PFS was 8.2 months for ola and BRCA1; PFS was 6.5 months for ola...
DOI:
10.1093/annonc/mdz268
Trial ID:
Title:
Lynparza approved in Japan for the treatment of advanced ovarian, prostate and pancreatic cancers
Excerpt:
AstraZeneca and MSD’s Lynparza (olaparib) has been approved in Japan for the treatment of advanced ovarian, prostate and pancreatic cancers….The three approvals authorise Lynparza for:...maintenance treatment after platinum-based chemotherapy for patients with BRCAm curatively unresectable pancreas cancer.
Source:
Title:
Study to Evaluate TNG348 Alone and With a PARP Inhibitor in Patients With BRCA 1/2 Mutant or HRD+ Solid Tumors
Excerpt:
...- All participants must have documented BRCA 1/2 mutant or other HRD+ in solid tumor, which is identified through a validated sequencing test...
Trial ID:
Source:
Title:
an open explorative phase II, open label study of olaparib in the treatment of advanced cancer in patients carrying a somatic or germline mutation in a homologous recombination gene.
Excerpt:
...1- Provision of informed consent prior to any study specific procedures 2- Female or male aged > 18 years 3- Histologically proven advanced cancer, either locally or metastatic, harboring a specific pathogenic genetic alteration (with the exception of breast, pancreas, ovarian or prostate cancer patients harboring a BRCA1/2 mutation) 4- No approved targeted therapy for the specific genetic alteration in the specific tumor type 5- No other genomic driven phase I, II or III trial available for the specific genomic alteration in the specific tumor type 6- Available tumor tissue for verification of the mutation by Sanger sequencing. ...
Trial ID:
More C2 evidence
Source:
Title:
Olaparib in the Treatment of BRCA1/2 Unmutated and BRCA1 Promoter Methylated Recurrent and Metastatic Triple-negative Breast Cancer
Excerpt:
...Histologically confirmed recurrent and metastatic TNBC patients without BRCA1/2 mutation and BRCA1 promoter methylation....
Trial ID:
Source:
Title:
Assessing the Efficacy of Paclitaxel and Olaparib in Comparison to Paclitaxel / Carboplatin Followed by Epirubicin/Cyclophosphamide as Neoadjuvant Chemotherapy in Patients With HER2-negative Early Breast Cancer and Homologous Recombination Deficiency
Excerpt:
...Assess the efficacy of olaparib in HER2-negative early Breast Cancer and HRD (BRCA 1/2 mutations and/or HRD positive). ...
Trial ID:
Source:
Title:
ANZ 1103 Study of Olaparib Clinical Effect in Patients with Breast Cancer or Ovarian Cancer
Excerpt:
......
Trial ID:
Source:
Title:
Olaparib in Locally Advanced ER, PgR and HER2 Negative (Triple Negative) and in Locally Advanced Germline BRCA Mutation-positive Breast Cancer Patients
Excerpt:
...- Germline BRCA1 or BRCA2 mutation that is considered deleterious or suspected deleterious (include those mutations or translocations termed "deleterious" or "suspected deleterious" according to lab reporting)....
Trial ID:
Source:
Title:
Olaparib as Adjuvant Treatment in Patients With Germline BRCA Mutated High Risk HER2 Negative Primary Breast Cancer
Excerpt:
...- Documented germline mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function)....
Trial ID:
Source:
Title:
Assessment of the Efficacy and Safety of Olaparib Monotherapy Versus Physicians Choice Chemotherapy in the Treatment of Metastatic Breast Cancer Patients With Germline BRCA1/2 Mutations.
Excerpt:
...- Germline mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious....
Trial ID:
Source:
Title:
Olaparib In Metastatic Breast Cancer
Excerpt:
...- Documented somatic mutation (deleterious or suspected deleterious) in BRCA1 or BRCA2 through any CLIA approved lab only if in addition to the lack of a germline BRCA1/2 mutation is demonstrated through a CLIA approved lab....
Trial ID:
Source:
Title:
Predicting Olaparib Sensitivity in Patients With Unresectable Locally Advanced/Metastatic HER2-negative Breast Cancer.
Excerpt:
......
Trial ID:
Source:
Title:
Olaparib in Combination With Carboplatin for Refractory or Recurrent Women s Cancers
Excerpt:
...Men with BRCA1/2 mutation and metastatic breast cancer will be eligible for study....
Trial ID:
Source:
Title:
AZD2281 Plus Carboplatin to Treat Breast and Ovarian Cancer
Excerpt:
...For patients enrolling in the sporadic serous epithelial ovarian cancer group, Group B, a negative family history (BRCAPRO score less than or equal to 20% or negative BRCA1/2 mutation test)....
Trial ID:
Source:
Title:
A Phase I, Open-Label, 2 Part Multicentre Study to Assess the Safety and Efficacy of Olaparib in Combination With Carboplatin in Patients With Advanced HER-2 Negative Breast Cancer
Excerpt:
...- Documented germline mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious...
Trial ID:
Source:
Title:
Radiation Therapy With or Without Olaparib in Treating Patients With Inflammatory Breast Cancer
Excerpt:
...Germline and somatic BRCA status (genetic testing) are planned for future correlative evaluation, in order to examine treatment and circulating tumor deoxyribonucleic acid (ctDNA) response as stratified by BRCA 1/2 mutational status....
Trial ID:
Source:
Title:
Analysis of Olaparib Response in Patients With BRCA1 and/or 2 Promoter Methylation Diagnosed of Advanced Breast Cancer
Excerpt:
...Absence of deleterious or suspected deleterious germline mutations in BRCA1 and BRCA2....
Trial ID:
Source:
Title:
Efficacy and Safety of Olaparib (MK-7339) in Participants With Previously Treated, Homologous Recombination Repair Mutation (HRRm) or Homologous Recombination Deficiency (HRD) Positive Advanced Cancer (MK-7339-002 / LYNK-002)
Excerpt:
...- For participants who have non-breast or -ovarian cancers that are breast cancer susceptibility gene 1/2 (BRCA1/2) mutated (BRCAm), or who have cancers that are BRCA1/2 non-mutated and homologous recombination repair nonmutated:...
Trial ID:
Less C2 evidence
Source:
Title:
Olaparib Use in Patients With Metastatic Breast Cancer Harboring Somatic BRCA1/2 Mutations or Mutations in Non-BRCA1/2, DNA Damage Repair Genes
Published date:
12/30/2021
Excerpt:
In this retrospective, single institution study, patients who were treated with off-label, off-protocol olaparib for metastatic breast cancer harboring sBRCA1/2 or germline or somatic non-BRCA1/2, HRR mutations were identified.....The median progression free survival in patients with a sBRCA1/2 mutation was 6.5 months (range 5-9 months) vs. 3 months (range 2-4 months) in patients with non-BRCA1/2, HRR mutations....This single institution experience adds to recent larger reports confirming evidence for PARPi therapy in patients with metastatic breast cancer harboring sBRCA1/2 mutations.
DOI:
10.1016/j.clbc.2021.12.007
Source:
Title:
TBCRC 048: A phase II study of olaparib monotherapy in metastatic breast cancer patients with germline or somatic mutations in DNA damage response (DDR) pathway genes (Olaparib Expanded).
Published date:
05/13/2020
Excerpt:
Patients received olaparib 300 mg...Responses were gene specific (Table): gPALB2 and sBRCA mutations predicted response…
DOI:
10.1200/JCO.2020.38.15_suppl.1002
Trial ID:
Source:
Title:
Olaparib monotherapy in pretreated patients with BRCA1/2 alterations: Results of a DRUP trial cohort.
Published date:
05/13/2020
Excerpt:
Nine different cancer types were included: prostate (n=11), breast (n=4), ovarian (n=2), pancreatic (n=3), colorectal (n=2), biliary tract (n=2), kidney (n=1), adrenal gland (n=1) and endometrial (n=1). The primary endpoint was clinical benefit (CB: objective response or stable disease (SD) ≥ 16 weeks). CB was observed in pts with both somatic and germline BRCA alterations and across tumor types.
DOI:
10.1200/JCO.2020.38.15_suppl.3633
Trial ID:
Source:
Title:
Inhibition of Poly(ADP-Ribose) Polymerase in Tumors from BRCA Mutation Carriers
Excerpt:
Of the three patients with BRCA2 breast cancer, one had a complete remission, according to RECIST, and another had stable disease for 7 months...The patient with BRCA2 breast cancer had a complete remission lasting for more than 60 weeks.
DOI:
10.1056/NEJMoa0900212
Trial ID:
Source:
Title:
TBCRC 048: Phase II Study of Olaparib for Metastatic Breast Cancer and Mutations in Homologous Recombination-Related Genes
Excerpt:
Patients received olaparib 300 mg orally twice a day until progression….In cohort 1, ORR was 33% (90% CI, 19% to 51%) and in cohort 2, 31% (90% CI, 15% to 49%). Confirmed responses were seen only with gPALB2 (ORR, 82%) and sBRCA1/2 (ORR, 50%) mutations....PARP inhibition is an effective treatment for patients with MBC and gPALB2 or sBRCA1/2 mutations, significantly expanding the population of patients with breast cancer likely to benefit from PARPi beyond gBRCA1/2 mutation carriers.
DOI:
10.1200/JCO.20.02151
Trial ID:
Source:
Title:
PSPC1 Inhibition Synergizes with Poly(ADP-ribose) Polymerase Inhibitors in a Preclinical Model of BRCA-Mutated Breast/Ovarian Cancer
Published date:
12/03/2023
Excerpt:
Here, we investigated the ability of paraspeckle component 1 (PSPC1), as an additional synthetic lethal partner with BRCA1/2, to enhance olaparib sensitivity in preclinical models of BRCA1/2-mutated breast and ovarian cancers. In vitro, the combined olaparib and PSPC1 small interfering RNA (siRNA) exhibited synergistic anti-proliferative activity in BRCA1/2-mutated breast and ovarian cancer cells. The combination therapy also demonstrated synergistic tumor inhibition in a xenograft mouse model.
DOI:
https://doi.org/10.3390/ijms242317086
Source:
Title:
Olaparib enhances sensitization of BRCA-proficient breast cancer cells to x-rays and protons
Published date:
10/30/2023
Excerpt:
Two BRCA-proficient BC cell lines, MDA-MB-231 and T47D BC, were used….MDA-MB-231 cells exhibited a higher dose enhancement factor for Olaparib than T47D cells. Olaparib increased radiation-induced G2/M cell cycle arrest and apoptosis specifically in MDA-MB-231 cells....This study found that Olaparib enhanced radiation efficacy in BRCA-proficient breast cancer cells...
DOI:
10.1007/s10549-023-07150-4
