“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.”
“Sequential doxorubicin plus cyclophosphamide followed by weekly paclitaxel is a reasonable adjuvant treatment option for triple-negative breast cancer, according to 12-year follow-up of the Eastern Cooperative Oncology Group’s E1199 phase III trial evaluating optimal taxane type and scheduling in operable breast cancer.
“No similar benefits were observed for patients with hormone receptor-positive tumors or disease not overexpressing HER-2, and obesity and black race were found to be independently associated with recurrence and death, reported investigators online in the Journal of Clinical Oncology.
” ‘Improved outcomes initially observed for weekly paclitaxel were qualitatively similar but quantitatively less pronounced with longer follow-up, although exploratory analysis suggested substantial benefit in triple-negative disease,’ wrote multicenter researchers led by Joseph A. Sparano, MD, a medical oncologist at Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, N.Y.
“Updating their 5-year findings, they reported on almost 5,000 eligible women with stage II-III breast cancer treated with four cycles of doxorubicin plus cyclophosphamide. The four-arm trial then randomly assigned them to receive paclitaxel or docetaxel on a standard schedule every three weeks for four doses, or weekly for 12 doses using a 2 x 2 factorial design, with the regimens designated as P3, P1, D3, and D1, respectively. The primary endpoint was disease-free survival (DFS).”
“The German Breast Group (GBG) presented two analyses that can serve as predictors of response to treatment by further subdividing preoperative (neoadjuvant) patients with HER 2 positive breast cancer and those with triple negative breast cancer based on tumor DNA repair capabilities and related factors.
“Prof. Dr. Gunter von Minckwitz, president of the GBG Research Institute, noted, ‘Taken together these studies demonstrate that a deeper understanding of the variations among breast cancer types that go beyond hormone response and BRCA gene mutations can inform treatment options with increased precision.’
“One study (Abstract No: 1004) fromlead author Dr. von Minckwitz found cancer-related BRCA mutations in the tumor are more common (30.3%) than inherited BRCA mutations (19.8%) in patients with triple-negative breast cancer. The homologous recombination (HR) assay measures DNA repair capacity beyond those related to BRCA mutation. HR deficiency defined as having either a BRCA mutation of the tumor or a high HR score was found in 70.5% of the patients. These findings can affect treatment options. Patients with a tumor BRCA mutation and/or a high HR score showed a high complete response to preoperative (neoadjuvant) chemotherapy. Our findings suggest those patients are also benefiting more from the additional use of carboplatin than tumors without HR deficiency.”
“Immunomedics, Inc., (IMMU) today announced that among 49 patients with metastatic triple-negative breast cancer (TNBC) evaluated for response to treatments with sacituzumab govitecan in a mid-stage clinical study, 31%, or 15 patients, showed a reduction in tumor size of 30% or more. They include 2 patients with complete response. Response assessments were based on the rules set by the Response Evaluation Criteria In Solid Tumors (RECIST 1.1). Adding the 22 patients with responses between less than 30% tumor shrinkage and less than 20% tumor increase, the disease control rate was 76%.
“Sacituzumab govitecan also produced significant duration of response in these responding patients. Measured as the time it takes from the beginning of sacituzumab govitecan treatments to when the cancer progresses, the median progression-free survival (PFS) for the 48 patients who received the optimal doses of 8 or 10 mg/kg was 6.0 months. Importantly, 63% of patients (22 of 35) had a time-to-progression longer than their last therapy, notwithstanding disease progression has not yet happened in 56% of patients at the time of analysis.
“These results were presented at the 2015 Annual Meeting of the American Society of Clinical Oncology by Dr. Aditya Bardia of Massachusetts General Hospital Cancer Center in Boston, MA, and a faculty member at Harvard Medical School, who commented, ‘Given that a majority of the patients enrolled into this study had failed 4 or more prior cancer therapies, some as many as 11, we are quite encouraged with sacituzumab govitecan in this late-stage setting in an aggressive disease that is difficult to treat.’ “
“Generex Biotechnology Corporation (www.generex.com) (OTCQB: GNBT) announced today that updated data from the on-going Phase II clinical trial of the AE37 breast cancer vaccine under development at the Company’s wholly-owned subsidiary, Antigen Express, Inc. (www.antigenexpress.com), will be presented at the upcoming annual meeting of the American Society of Clinical Oncology (ASCO). The current analysis was performed on data that was examined one year after the last patient was enrolled into the trial. The ASCO meeting will be held from May 29 to June 2, 2015 in Chicago, IL.
“The abstract, entitled ‘Final Pre-specified Analysis of the Phase II Trial of the AE37+GM-CSF Vaccine in High Risk Breast Cancer Patients to Prevent Recurrence”, by Julia Greene, et al will be presented on May 30 during the Breast Cancer – HER2/ER session. The study reports on the anticipated five year disease free survival in patients enrolled in a controlled, randomized, and single-blinded Phase II trial that completed enrollment in January of 2014. A prior interim analysis conducted in 2011, as well as a primary efficacy analysis conducted in 2013, pointed to a benefit of the AE37 vaccine in patients not receiving Herceptin and, in particular, patients with triple negative breast cancer. This latter group represents a patient population of high unmet need. The present study continues to show a trend in this population, with a 35% reduction in the relative risk of recurrence in patients receiving the AE37 vaccine.”
“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.’ “