News - BRCA1 mutation + ATM mutation

2ms

TRITON3: A Study of Rucaparib Versus Physician's Choice of Therapy in Participants With Metastatic Castration-resistant Prostate Cancer and Homologous Recombination Gene Deficiency (clinicaltrials.gov)

P3, N=405, Active, not recruiting, pharmaand GmbH | Trial completion date: Mar 2024 --> Dec 2024

2 months ago

Trial completion date • Metastases

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • BRCA (Breast cancer early onset)

BRCA2 mutation • BRCA1 mutation • ATM mutation • BRCA1 mutation + ATM mutation

docetaxel • Xtandi (enzalutamide capsule) • Rubraca (rucaparib) • abiraterone acetate

5ms

BRCAAway: A randomized phase 2 trial of abiraterone, olaparib, or abiraterone + olaparib in patients with metastatic castration-resistant prostate cancer (mCRPC) bearing homologous recombination-repair mutations (HRRm). (ASCO-GU 2024)

Median age: 67 years (range 42-85); 55 White, 6 Black; prior Docetaxel 26% for mHSPC, Darolutamide/Enzalutamide 3.3% for nmCRPC; disease sites: bone n=44, viscera n=12, lymph node n=31, other n=3; median baseline PSA: 14 ng/ml (range 0.15-4,037 ng/ml). In mCRPC pts with BRCA1/2 or ATM alterations, abiraterone/prednisone + olaparib was well tolerated and resulted in a longer PFS vs either agent alone or sequentially. Clinical trial information: NCT03012321.

5 months ago

Clinical • P2 data • BRCA Biomarker • PARP Biomarker • Metastases

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency)

BRCA2 mutation • BRCA1 mutation • ATM mutation • BRCA1 mutation + ATM mutation

Lynparza (olaparib) • docetaxel • Xtandi (enzalutamide capsule) • abiraterone acetate • Nubeqa (darolutamide)

7ms

Mutations in TP53 and DNA damage repair genes have a negative impact on the response to first-line systemic therapy in men with prostate cancer (DGHO 2023)

The impact of DDR gene or TP53 mutations on progression-free survival (PFS) under first-line systemic therapy (androgen deprivation therapy, ADT, n= 84, 48.3%; ADT plus docetaxel, n=76, 43.7%; ADT plus abiraterone or enzalutamide, n=14, 8%) as well as the overall survival (OS) was assessed. Patients with hormone-sensitive prostate cancer and mutations in BRCA1/2, ATM or TP53 show a poorer PFS and OS when compared to patients with other DDR gene mutations or no mutation. These patients also show a trend towards a more unfavorable PFS under standard first-line treatment. Our results argue in favor of a more intensified first-line treatment in these patients possibly under inclusion of PARP inhibitors or platinum compounds.

7 months ago

Clinical • BRCA Biomarker • PARP Biomarker

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase)

TP53 mutation • BRCA2 mutation • BRCA1 mutation • ATM mutation • BRCA1 mutation + ATM mutation

docetaxel • Xtandi (enzalutamide capsule) • abiraterone acetate

9ms

P3, N=405, Active, not recruiting, zr Pharma & GmbH | Trial completion date: Mar 2023 --> Mar 2024

9 months ago

Trial completion date • Metastases

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • BRCA (Breast cancer early onset)

BRCA2 mutation • BRCA1 mutation • ATM mutation • BRCA1 mutation + ATM mutation

docetaxel • Xtandi (enzalutamide capsule) • Rubraca (rucaparib) • abiraterone acetate

over1year

Role of Rucaparib in the Treatment of Prostate Cancer: Clinical Perspectives and Considerations. (PubMed, Cancer Manag Res)

We also compared rucaparib's use and safety profile with Olaparib, niraparib and talazoparib, three other PARP inhibitors tested for the treatment of mCRPC. Finally, more research is needed to elucidate rucaparib's effect on HRR mutations other than BRCA1/2. Advancements in understanding the genetic landscape of mCRPC will also assist in understanding rucaparib's full therapeutic potential.

over 1 year ago

Review • Journal • BRCA Biomarker • PARP Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency)

BRCA2 mutation • BRCA1 mutation • ATM mutation • BRCA1 mutation + ATM mutation

Lynparza (olaparib) • Talzenna (talazoparib) • Zejula (niraparib) • Rubraca (rucaparib)

over1year

Somatic genomic landscape of East Asian epithelial ovarian carcinoma and its clinical implications from prospective clinical sequencing; A Korean Gynecologic Oncology Group study (KGOG 3047). (PubMed, Int J Cancer)

Furthermore, we utilized machine-learning algorithms to identify molecular correlates that conferred increased sensitivity to platinum and olaparib treatments including somatic mutations in BRCA1, ATM, and MYC. Conversely, patients with ALK mutation were considerably resistant to both treatment modalities. Collectively, our results demonstrate the clinical feasibility of prospective genetic sequencing to facilitate personalized treatment opportunities for patients with EOC.

over 1 year ago

Journal • BRCA Biomarker • PARP Biomarker

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • NOTCH1 (Notch 1)

TP53 mutation • KRAS mutation • BRCA1 mutation • BRAF mutation • PIK3CA mutation • ATM mutation • ARID1A mutation • ALK mutation • CDKN2A mutation • BRCA1 mutation + ATM mutation

Lynparza (olaparib)

2years

TRITON3: A Study of Rucaparib Versus Physician's Choice of Therapy in Patients With Metastatic Castration-resistant Prostate Cancer and Homologous Recombination Gene Deficiency (clinicaltrials.gov)

P3, N=405, Active, not recruiting, Clovis Oncology, Inc. | Recruiting --> Active, not recruiting | Trial completion date: Apr 2022 --> Mar 2023 | Trial primary completion date: Feb 2022 --> Jun 2022

2 years ago

Enrollment closed • Trial completion date • Trial primary completion date

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase)

BRCA2 mutation • BRCA1 mutation • ATM mutation • BRCA1 mutation + ATM mutation

docetaxel • Xtandi (enzalutamide capsule) • Rubraca (rucaparib) • abiraterone acetate