“A combination treatment composed of the PARP inhibitor olaparib and the investigational PI3K inhibitor BKM120 demonstrated activity and safety for women with triple-negative breast cancer or high-grade serous ovarian cancer, according to study findings presented at the American Association for Cancer Research Annual Meeting.
“High-grade serous ovarian cancer and triple-negative breast cancer are similar in that they often have germline BRCA mutations, have a sensitivity to platinum agents and have high copy number alterations based on The Cancer Genome Atlas, according to study background. Further, preclinical data have suggested olaparib (Lynparza, AstraZeneca) is synergistic with BKM120 (Novartis) and BYL719 (Novartis) in both cancers.
“Ursula A. Matulonis, MD, medical director of gynecologic oncology at the Susan F. Smith Center for Women’s Cancers at Dana-Farber Cancer Institute and associate professor of medicine at Harvard University Medical School, and colleagues evaluated olaparib plus BKM120 in 12 patients with triple-negative breast cancer and 34 patients with high-grade serous ovarian cancer. Thirty-five patients had germline BRCA mutations.
“ ‘This is one area where we in ovarian cancer are in the forefront,’ Matulonis said during a press conference. ‘We are using an FDA-approved biomarker through germline BRCA status to basically say when a patient is eligible to receive olaparib.’ “
University of North Carolina at Chapel Hill School of Medicine | Apr 23, 2015
“No approved targeted therapies exist to treat triple-negative breast cancer, but new chemotherapeutic treatment strategies are helping shrink tumors so that less breast tissue needs to be removed during surgery. New research led by Brigham and Women’s Hospital in collaboration with the UNC Lineberger Comprehensive Cancer Center finds that breast-conserving therapy – or the removal of less breast tissue via a lumpectomy – was successful in more than 90 percent of the women who became eligible for this procedure after treatment with chemotherapy. Despite these findings, 31 percent who were eligible for breast conserving therapy chose to have the entire breast removed via mastectomy.
“The complete manuscript of this study and its presentation at the American Surgical Association’s 135th annual meeting today in San Diego, California, is anticipated to be published in the Annals of Surgery pending editorial review.
“ ‘We’ve shown that we can offer breast-conserving therapy to more women using these drug combinations, and if they convert, we’re really successful,’ said senior author David Ollila, MD, James and Jesse Millis Distinguished Professor of Surgery at University of North Carolina School of Medicine, co-director of the UNC Breast Program and a member of the UNC Lineberger Comprehensive Cancer Center. ‘We have more and more women eligible for breast preservation, and still we saw more than 30 percent of women choosing mastectomy.’ “
“Combination treatment with the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib plus the phosphatidylinositol 3-kinase (PI3K) inhibitor BKM120 resulted in clinical activity in women with triple-negative breast cancer and those with high-grade serous ovarian cancer.
“Patients that had BRCA-mutant and BRCA wild-type tumors responded to the treatment.
“The results of this phase I trial were presented at a press briefing at the American Association for Cancer Research (AACR) Annual Meeting, held April 18 to 22 in Philadelphia.”
“Early data in a preliminary human study show that an experimental immune system drug is generally safe and well tolerated in women with metastatic, triple-negative breast cancer, a persistently difficult form of the disease to treat.
“Results of the early-phase clinical trial of the therapy, called MPDL3280A, which aims to restore the immune system’s ability to recognize and attack cancer cells, are expected to be presented at the American Association for Cancer Research’s 2015 Annual Meeting in Philadelphia from April 18-22. Triple-negative breast cancer cells lack expression of estrogen receptor, progesterone receptor and HER2 protein, the established targets for breast cancer therapies.
“The small study was conducted on 54 patients treated at the Johns Hopkins Kimmel Cancer Center and several other institutions.
” ‘Early data in this trial show that the drug is generally safe and well-tolerated, and it appears to be able to control disease in some of these patients,’ says Leisha Emens, M.D., Ph.D., an associate professor of oncology at the Johns Hopkins University School of Medicine. ‘Now we’ll need to test it further in more patients and compare it with standard therapies to establish its therapeutic value.’ “
“Roche Holding AG will skip a mid-stage study of an experimental immunotherapy for breast cancer and proceed directly to a phase 3 trial later this year.
“The Swiss company will study MPDL3280A for triple-negative breast cancer, which is currently treated mostly with chemotherapy, spokeswoman Holli Dickson said in a phone interview. The drug will be tested in combination with chemotherapy.
“The company will present results from an early-stage study of the drug at a cancer meeting in Philadelphia on April 20. Roche is competing with Merck & Co. to develop a drug for a segment of the breast cancer market that may reach as much as $5 billion in peak sales, according to Goldman Sachs Group Inc. analysts.”
“Cisplatin plus gemcitabine demonstrated superior PFS outcomes compared with paclitaxel plus gemcitabine for women with metastatic triple-negative breast cancer, according to results of a randomized phase 3 study.
“ ‘Despite general improvements in the management of breast cancer, triple-negative breast cancer represents a continuing challenge because, when compared with other subtypes, it is associated with a higher frequency of recurrence, shorter DFS and poor OS, despite similar therapeutic approaches to other breast cancers,’ Xi-Chun Hu, MD, of the department of medical oncology at the Fudan University Shanghai Medical College, and colleagues wrote. ‘The median distant disease-free interval for relapsed triple-negative breast cancer is about 1 to 2 years and the median survival for metastatic triple-negative breast cancer is about 1 year.’
“Hu and colleagues evaluated data from 236 patients (median age, 47 years) from 12 institutions or hospitals within the Chinese Breast Cancer Study Group. Patients had not undergone previous chemotherapy for metastatic disease and they had an ECOG performance status of 0 to 1.
“Researchers randomly assigned patients 1:1 to a chemotherapy regimen of 1,250 mg/m2 gemcitabine on days 1 and 8 plus 75 mg/m2 cisplatin or 175 mg/m2 paclitaxel on day 1 for eight 3-week cycles.”
“Celldex Therapeutics has reported positive data from the Phase II EMERGE trial of glembatumumab vedotin, an antibody-drug conjugate, in patients with metastatic breast cancer.
“Data from this trial supported the initiation of the ongoing, pivotal Phase II METRIC trial in patients with triple negative breast cancers that over-express glycoprotein NMB (gpNMB).
“Glembatumumab vedotin targets and binds to gpNMB, a protein expressed by multiple tumor types, including breast cancer.
“A total of 124 patients with advanced, heavily pre-treated breast cancer were enrolled in the randomized, multi-center, controlled EMERGE trial and they were randomized (2:1) to receive glembatumumab vedotin or ‘Investigator’s Choice’ (IC) single agent, approved chemotherapy.”
“At Ricki Fairley’s annual check-up in 2012, doctors found a tiny lump. She was diagnosed with triple negative breast cancer, a less common and more aggressive form of the disease that has very few treatment options. Approximately 15 percent of all breast cancer cases are categorized as triple negative.
“Triple negative breast cancer can be effectively treated if the disease is caught early, and Fairley, now 58 years old, is living proof. She underwent a long course of aggressive chemotherapy and radiation and is now doing well.
“Triple negative is one of four subtypes of breast cancer, and a new report emphasizes how important it is for doctors to identify the risks and treatments for each. For example, triple negative cancers do not respond to certain hormonal therapies that can help other women.
“The nationwide data — published in the Journal of the National Cancer Institute and co-authored by the American Association of Central Cancer Registries, the American Cancer Society, the Centers for Disease Control and Prevention, and the National Cancer Institute at the National Institutes of Health — may help doctors identify which patients are at most risk for each type of breast cancer and which treatments may be most effective.”
“Australian researchers have found that so-called ‘triple-negative breast cancers’ are two distinct diseases that likely originate from different cell types. This helps explain why survival prospects for women with the diagnosis tend to be either very good or very bad.
“The Sydney-based research team has found a gene that drives the aggressive disease, and hopes to find a way to ‘switch it off’.