Olaparib Maintenance for Ovarian Cancer Most Effective in Women with BRCA Mutations

Editor’s note: After initial treatment, some cancer patients receive maintenance therapy to keep their cancer from returning. In a recent clinical trial with volunteer patients, scientists tested the effectiveness of maintenance therapy for platinum-sensitive recurrent serous ovarian cancer. Some of the women had BRCA1 or BRCA2 mutations, and some did not. Also, all of the women had previously been treated with platinum-based chemotherapy, and experienced tumor shrinkage or complete disappearance of their tumors. In the clinical trial, scientists randomly divided the women into two groups. One group received maintenance therapy with the drug olaparib, and for comparison, the other group was treated with a “fake” placebo drug. The scientists found that women with BRCA1 or BRCA2 mutations were more likely to benefit from the maintenance therapy treatment than women without BRCA mutations.

“Women with platinum-sensitive recurrent serous ovarian cancer who harbored BRCA mutations are more likely than BRCA wild-type patients to benefit from maintenance monotherapy with olaparib, results of a phase 2 study suggest.

“ ‘To our knowledge, our study is the first phase 2 trial in ovarian cancer to show that patients with BRCA1 or BRCA2 mutations respond preferentially to a PARP inhibitor,’ Jonathan Ledermann, MD, of UCL Cancer Institute at University College London, and colleagues wrote.

“Ledermann and colleagues conducted a randomized, double blind study that included 265 women with platinum-sensitive recurrent serous ovarian cancer. All patients received at least two platinum-based regimens and demonstrated a complete or partial response to their most recent platinum-based regimen.”


Faster Genetic Testing Method will Likely Transform Care for Many Patients with Breast Cancer

“When a woman is diagnosed with breast cancer, it’s important to know as much about her tumour as possible to determine the best treatment. Most cases of breast cancer are sporadic, but a minority are hereditary and caused by one or more mutations in genes such as BRCA1 or BRCA2. To find such genetic mutations in newly diagnosed patients, researchers must sequence the woman’s DNA, which is generally a relatively slow process that generates results weeks or months after patients have started treatment. Next generation sequencing (NGS) is a newer method of sequencing DNA that processes large amounts of data. It’s faster and more expensive than conventional sequencing, but in recent years it has become cheaper and more widely accessible by rapid advances in computing power. With the use of NGS, which will soon become the mainstay of clinical genetics, breast cancer units will likely be able to get the results of genetic testing before patients begin their breast cancer treatment.”


The Poly(ADP-Ribose) Polymerase Inhibitor Niraparib (MK4827) in BRCA Mutation Carriers and Patients with Sporadic Cancer: A Phase 1 Dose-Escalation Trial

“Niraparib (MK4827) is an oral potent, selective PARP-1 and PARP-2 inhibitor that induces synthetic lethality in preclinical tumour models with loss of BRCA and PTEN function. Its safety, tolerability, maximum tolerated dose, pharmacokinetic and pharmacodynamic profiles were investigated in a Phase I trial for advanced prostate, lung and ovarian cancer. Patient cohorts were enriched for mutations in BRCA1 or BRCA2. Niraparib should be further assessed in inherited and sporadic cancers with homologous recombination DNA repair defects and to target PARP-mediated transcription in cancer.”


The poly(ADP-ribose) polymerase inhibitor niraparib (MK4827) in BRCA mutation carriers and patients with sporadic cancer: a phase 1 dose-escalation trial

“Poly(ADP-ribose) polymerase (PARP) is implicated in DNA repair and transcription regulation. Niraparib (MK4827) is an oral potent, selective PARP-1 and PARP-2 inhibitor that induces synthetic lethality in preclinical tumour models with loss of BRCA and PTEN function. We investigated the safety, tolerability, maximum tolerated dose, pharmacokinetic and pharmacodynamic profiles, and preliminary antitumour activity of niraparib.”


Role of Engrailed-2 (EN2) as a Prostate Cancer Detection Biomarker in Genetically High Risk Men

“Controversy surrounds the use of PSA as a biomarker for prostate cancer detection, leaving an unmet need for a novel biomarker in this setting; urinary EN2 may identify individuals with clinically relevant prostate cancer. Male BRCA1 and BRCA2 mutation carriers are at increased risk of clinically significant prostate cancer and may benefit from screening. Urine samples from 413 BRCA1 and BRCA2 mutation carriers and controls were evaluated. Subjects underwent annual PSA screening with diagnostic biopsy triggered by PSA > 3.0 ng/ml; 21 men were diagnosed with prostate cancer. Urinary EN2 levels were measured by ELISA and had a sensitivity of 66.7% and specificity of 89.3% for cancer detection. There was no statistically significant difference in EN2 levels according to genetic status or Gleason score. Urinary EN2 may be useful as a non-invasive early biomarker for prostate cancer detection in genetically high-risk individuals.”


Promise for BRCA-Defective Cancers

“Germline mutations of either BRCA1 or BRAC2 are particularly associated with an increased risk for breast and ovarian cancer. The initial results of a Phase I/II trial reported at the annual meeting of the American Society of Clinical Oncology indicate that a new drug, BMN-673, developed by BioMarin Pharmaceuticals in…”


Promise for BRCA-Defective Cancers

“Germline mutations of either BRCA1 or BRAC2 are particularly associated with an increased risk for breast and ovarian cancer. The initial results of a Phase I/II trial reported at the annual meeting of the American Society of Clinical Oncology indicate that a new drug, BMN-673, developed by BioMarin Pharmaceuticals in…”


First Man Has Prostatectomy Because of BRCA Gene Mutation

The first man has undergone prostatectomy after finding that out that he carries the BRCA2 gene mutation. BRCA gene mutations increase the risk for a number of cancers, including prostate cancer. They were in the news last week after superstar Angelina Jolie announced that she had a prophylactic mastectomy to avoid breast cancer.


PARP Inhibitor Shows Activity in Pancreatic, Prostate Cancers Among Patients Carrying BRCA Mutations

In the largest clinical trial to date to examine the efficacy of PARP inhibitor therapy in BRCA 1/2 carriers with diseases other than breast and ovarian cancer, the oral drug olaparib was found to be effective against advanced pancreatic and…