“The now-published results from the EMBRACA study confirm that talazoparib (Pfizer), a poly-adenosine diphosphate-ribose polymerase (PARP) inhibitor, prolongs progression-free survival (PFS) in patients with advanced BCRA-positive breast cancer compared with single-agent chemotherapy alone, and that it also significantly improves quality of life.
” ‘This is the largest randomized trial in BRCA mutation carriers [ever undertaken] and demonstrates PARP efficacy,’ Jennifer Litton, MD, associate professor in the Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, told Medscape Medical News in an email.”
“A new drug application (NDA) for the PARP inhibitor talazoparib has been granted a priority review by the FDA for the treatment of patients with germline BRCA mutation–positive, HER2-negative locally advanced or metastatic breast cancer, according to Pfizer, the manufacturer of the agent.
“In results from the phase III EMBRACA trial, on which the application is based, talazoparib reduced risk of disease progression or death by 46% compared with chemotherapy in patients with BRCA-positive advanced breast cancer. At a median follow-up of 11.2 months, the Median progression-free survival (PFS) at the median follow-up of 11.2 months was 8.6 months (95% CI, 7.2-9.3) with talazoparib versus 5.6 months (95% CI, 4.2-6.7) with physician’s choice of therapy (HR, 0.54; 95% CI, 0.41-0.71; P <.0001). The objective response rate (ORR) was 62.6% (95% CI, 55.8-69.0) compared with 27.2% (95% CI, 19.3-36.3), respectively (odds ratio, 4.99; 95% CI, 2.9-8.8; 2-sided P value <.0001).”
“In a small Phase II study of early-stage breast cancer patients with BRCA1/2 mutations, researchers at The University of Texas MD Anderson Cancer Center found that more than half of the women who took the PARP inhibitor talazoparib once daily prior to surgery had no evidence of disease at the time of surgery. If further validated in larger, confirmatory trials, the oral medication could replace chemotherapy for these patients.
“The trial, which expands upon a feasibility study published in npj Breast Cancer, was presented today as an oral presentation at the 2018 American Society of Clinical Oncology Annual Meeting by Jennifer Litton, M.D., associate professor of Breast Medical Oncology.”
“Approximately 5% of patients with sporadic breast cancer harbor mutations in BRCA1 or BRCA2; genes that are involved in the DNA repair process. Several phase I/II clinical studies have shown activity of single agent poly(ADP-ribose) polymerase (PARP) inhibitors in patients with metastatic breast cancer (MBC) and BRCA1/2 mutations. Recently in the randomized phase III OlympiAD trial, the PARP inhibitor olaparib improved progression-free survival (PFS) by 2.8 months over standard chemotherapy in patients with human epidermal growth factor 2 (HER2)–negative MBC and germline BRCA mutations.”
“The PARP inhibitor talazoparib significantly increased progression-free survival (PFS) over physician’s choice of therapy in a randomized phase III trial of patients with advanced breast cancer and a germline BRCA mutation.
“ ‘Talazoparib is a highly potent, dual-mechanism PARP inhibitor. It prevents the repair of DNA damage, and results in cell death,’ said Jennifer K. Litton, MD, of the University of Texas MD Anderson Cancer Center in Houston. A previous phase II study showed encouraging efficacy with the agent in patients with BRCA1/2 mutations, which led to the new EMBRACA trial. Litton presented results of the trial at the 2017 San Antonio Breast Cancer Symposium (SABCS), held December 5–9.”
Non-metastatic breast cancers are most often treated with surgery, but if the tumors are fairly large, or involve nearby lymph nodes, neoadjuvant (pre-operative) treatments with chemotherapy (NAC) are done first. NAC often reduces the tumor size and kills cancer cells in lymph nodes, if present, prior to surgery, improving the outcome. The best possible result of neoadjuvant treatment is pCR (pathologic compete response), when the tumor is no longer visible in imaging studies. Here, I review the new directions in which neoadjuvant treatments are evolving.
Today, treatments for metastatic breast cancers are tailored for specific subtypes. Starting with the introduction of the drug trastuzumab (Herceptin) for HER2-positive cancers, new, more specific treatment options were eventually developed and approved for other types as well. Estrogen deprivation endocrine therapies, lately prescribed in combination with CDK4/6 inhibitors, are used in estrogen receptor (ER)-positive cancers. Triple negative cancers (TNBC) are still treated mostly with chemotherapy, but immune checkpoint drugs and PARP inhibitors are explored in clinical trials, with some successes reported.
However, neoadjuvant treatments (except for HER2+ cancers) remain largely limited to chemotherapy regimens. This is starting to change now, with new approaches tailored to the cancer type being investigated in clinical trials.
In this regard, it is important to mention the I-SPY2 trial, NCT01042379, which started in 2010 and is for women with stage II-III breast cancer. It offers about a dozen drugs that are chosen based on particular features of the newly diagnosed cancers. This trial has a unique design and has produced some important results. Additional treatments and trials for various types of breast cancer are discussed below. Continue reading…
Last month, the annual American Society of Clinical Oncology (ASCO) meeting took place in Chicago. Thousands of oncologists, patients, and journalists gathered to learn about the most recent developments in cancer research and treatment. Here are some breast cancer highlights from the meeting:
Triple negative breast cancer (TNBC) is considered more responsive to treatment with immune checkpoint drugs than any other type of breast cancer. So far, these drugs have primarily been explored in metastatic TNBC, in combination with chemotherapy. The combination of “anti-PD-L1” and “anti-PD-1” immune checkpoint drugs with chemotherapy has now been examined in early-stage TNBC, in which a breast tumor can be surgically removed after neoadjuvant chemotherapy. Continue reading…
“Pfizer Inc. (NYSE:PFE) today announced Phase 2 data showing that its investigational, dual-mechanism poly ADP ribose polymerase (PARP) inhibitor, talazoparib, demonstrated anti-tumor activity in patients with germline (inherited) BRCA1/2-positive (gBRCA+) advanced breast cancer. Results from the Phase 2 ABRAZO trial were presented during an oral session at the 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago.”
“All 13 newly diagnosed breast cancer patients with BRCA mutations had their tumors shrink significantly when treated with a PARP inhibitor ahead of frontline presurgical chemotherapy in a pilot study at The University of Texas MD Anderson Cancer Center.
“Tumor shrinkage after two months of treatment with the PARP inhibitor talazoparib, measured by ultrasound, ranged from 30 to 98 percent with an average reduction in tumor volume of 78 percent among the 13 patients.”