“New research published in the March 2016 issue of The FASEB Journal, shows that a commonly prescribed class of high blood pressure drugs may have the potential to slow the growth of triple negative breast cancer tumors. These drugs, called ‘beta blockers’ work by counteracting the pro-growth effect caused by adrenaline by affecting the the beta2-adrenoceptor.
” ‘Previous studies have linked increased stress with accelerated onset of metastasis in some forms of breast cancer,’ said Michelle L. Halls, Ph.D., a researcher involved in the work from the Drug Discovery Biology Theme at Monash Institute of Pharmaceutical Sciences at Monash University in Parkville, Victoria, Australia. ‘By understanding how stress accelerates invasion in aggressive breast tumor cells, this work will inform future studies into whether beta-blockers could be a useful adjuvant therapy in the treatment of some aggressive breast cancers.’ “
“The FDA has granted sacituzumab govitecan (IMMU-132) breakthrough therapy designation for the treatment of patients with triple-negative breast cancer (TNBC) following at least 2 treatments for metastatic disease, according to Immunomedics, the manufacturer of the investigational antibody-drug conjugate.
“The designation, which will expedite the development and review of sacituzumab govitecan in TNBC, is based on a phase II trial in which the therapy induced a response rate of 31% in heavily pretreated patients with metastatic TNBC.
“ ‘We believe breakthrough therapy designation for IMMU-132 further validates this potential therapeutic for patients with TNBC, and we are delighted to receive this important recognition,’ Cynthia L. Sullivan, president and chief executive officer, of Immunomedics, said in a statement. ‘We continue to assess partnering opportunities while completing the scale-up manufacturing and regulatory activities for an international, randomized, controlled, registration trial in TNBC, based on the special protocol assessment agreement that was already granted by the FDA,’ she added.”
TNBC has long been considered to be more amenable to immune system-based treatments than other types of breast cancer because it is more immunogenic; that is, relatively high levels of immune cells accumulate within or adjacent to TNBC tumors. These immune cells could be triggered to attack tumors if properly activated. TNBC tumors are also likely to have a higher mutational burden (number of genetic mutations). This is one of the predictors of sensitivity to a type of treatment called immune checkpoint blockade. Drugs known as checkpoint inhibitors block the proteins PD-1 or PD-L1. In cancer, PD-L1 proteins on tumor cells bind to PD-1 proteins on immune T cells and inhibit their tumor-killing activity. Immune checkpoint drugs disable this interaction and enable activation of T cells. These drugs are actively being explored in TNBC in clinical trials.
“Upfront treatment with the PD-L1 inhibitor atezolizumab (MPDL3280A) plus nab-paclitaxel (Abraxane) showed a confirmed objective response rate (ORR) of 66.7% in patients with metastatic triple-negative breast cancer (TNBC), according to data presented at the 2015 San Antonio Breast Cancer Symposium.
“In the phase Ib study, atezolizumab plus nab-paclitaxel was explored across several lines of treatment regardless of PD-L1 status for patients with metastatic TNBC. In the second-line setting, the confirmed ORR was 25% and in the third-line and beyond the ORR was 28.6%. Across the full trial, the ORR was 41.7%.
“ ‘For the efficacy, we saw a very high response rate, which is extremely exciting and encouraging,’ said lead investigator Sylvia Adams, MD, associate professor of Medicine, NYU Perlmutter Cancer Center. ‘The combination was well-tolerated without additive toxicity. We saw only toxicity that was predictable for the single agents alone.’ “
“The treatment paradigm for patients with triple-negative breast cancer is set to undergo a dramatic transformation, as standard chemotherapeutic approaches are perfected and novel antibody-drug conjugates are developed.
“The treatment paradigm for patients with triple-negative breast cancer (TNBC) is set to undergo a dramatic transformation, as standard chemotherapeutic approaches are perfected and novel antibody-drug conjugates (ADCs) are developed. Kimberly Blackwell addressed this topic at the 2015 Chemotherapy Foundation Symposium, a meeting of over 1,000 oncologists and oncology professionals in New York City in November.
“ ‘I think we will see significant improvements in triple-negative breast cancer within the next few years,’ said Blackwell, an oncologist at the Duke Cancer Institute. ‘There are two ADCs that I am fairly excited about that are in late stage development.’ “
“IMMU-132, an anti-Trop-2 antibody-drug conjugate (ADC) was safe, tolerable, and yielded meaningful clinical activity in heavily pretreated patients with metastatic triple-negative breast cancer (TNBC), according to data from a phase II clinical trial presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, held Nov. 5–9.
” ‘TNBC comprises about 15 to 20 percent of all invasive breast cancers diagnosed in the United States and is more prevalent in young and African-American women. It has a high recurrence rate and is perhaps the most difficult type of breast cancer to treat successfully with current cytotoxic agents. Currently, there are no targeted treatments available for TNBC,’ said Aditya Bardia, MD, MPH, assistant professor of medicine at Harvard Medical School, and attending physician of medical oncology at the Massachusetts General Hospital Cancer Center in Boston.”
“Immunomedics, Inc. (Nasdaq: IMMU) today announced that patients with metastatic triple-negative breast cancer (TNBC) lived for a median of seven months without tumor progression, after receiving at least 3 doses of sacituzumab govitecan, the Company’s lead investigational antibody-drug conjugate (ADC) for solid cancer therapy, in a Phase 2 clinical study. The study also indicated that the responses were very durable, showing a median time-to-progression, based on computed tomography, of 9.4 months (range of 1.8+ to 13.2+ months), which included patients with stable disease, and partial and complete responses.
” ‘Patients in this late-stage setting usually have a median PFS of three to four months when treated with other agents,’ stated Aditya Bardia, MD, MPH, Assistant Professor of Medicine at Harvard Medical School, Attending Physician at the Massachusetts General Hospital Cancer Center in Boston, and an investigator in this trial. ‘Sacituzumab govitecan is a promising agent that offers hope for these patients with poor prognosis,’ Dr. Bardia added.”
“Adjuvant radiation therapy (RT) after lumpectomy for elderly women with early stage triple negative breast cancer (TNBC) improved overall survival (OS) and disease specific survival (DSS), a retrospective analysis of cases from the Surveillance, Epidemiology, and End Result (SEER) database has shown.
“The review showed that adjuvant radiation was associated with an overall six-fold decrease in any death, as well as death from breast cancer, Sean Szeja, MD, of The University of Texas Medical Branch at Galveston, and colleagues reported in a poster session at the American Society of Clinical Oncology (ASCO) Breast Cancer Symposium (Sept. 25-27).
“Some 23 months after diagnosis, 98.2% of women who received lumpectomy and radiation were alive, compared with 85.6% of those who received lumpectomy alone, the investigators said. In addition, the analysis revealed that breast cancer-related deaths were more common in the lumpectomy only group (6%) compared with the lumpectomy and radiation group (1%).”
“Rita Nanda, MD, assistant professor of Medicine, associate director, Breast Medical Oncology, The University of Chicago Medicine, discusses the efficacy of pembrolizumab and atezolizumab for the treatment of patients with metastatic triple-negative breast cancer (TNBC).
“Response rates seen with the two immunotherapy agents in two separate clinical trials in a heavily pretreated metastatic population was slightly under 20%, Nanda explains. This is significant due to how heavily pretreated these patients were, she adds.
“Furthermore, these responses were found to be durable and lasted up to 40 weeks. Both pembrolizumab and atezolizumab were shown to be well-tolerated. Patients experienced low-grade toxicities that were easily managed.”