We are reblogging this excellent post from Joan at SHARE. She focuses on the issues that apply to metastatic patients and is informative and easy to read. Thank you, Joan.
from SHARE blog:
Joan is a SHARE helpline volunteer and co-chair of SHARE Leaders, consumer reviewer for the Department of Defense, Breast Cancer Research Program
This year’s annual San Antonio Breast Cancer Symposium was busy as usual with many oncologists and scientists from around the world presenting clinical trial results and discussing the development of new treatments and care of patients and survivors. Some clinical trials showed promise in treating women with metastatic breast cancer.
Perjeta Brightens Outlook of HER2+ Survivors
The long awaited results for overall survival (OS) in the CLEOPATRA trial showed that Perjeta extended overall survival in metastatic HER2-positive breast cancer patients.
The drug maker made the announcement about the phase 3 trial at the symposium.
The combination of Perjeta, Herceptin, and Taxotere significantly improved OS by 34%, compared to Herceptin, Taxotere, and a placebo. As of the analysis, the median OS of patients in the treatment arm had not yet been reached, as half of those patients continued to survive. In the control arm, it was 37.6 months. As a result of the survival benefit, patients in the placebo arm were allowed to cross over to the Perjeta arm.
Perjeta was FDA approved in June for first-line treatment when it met the trial’s primary endpoint of progression-free survival (PFS). The drug improved PFS by 6 months, from 12.4 months in the standard arm to 18.5 months in the experimental arm.
In the current analysis, the Grade 3 side effects of neutropenia (low white-cell count) and diarrhea remained the same as in the initial report in June. Although Herceptin may cause congestive heart failure, the addition of Perjeta did not increase the chance of heart problems.
Genentech, which makes Perjecta, expects the FDA to approve T-DMI in the first quarter of 2013. T-DM1 is another drug that has also shown benefit in women with advanced HER2+ breast cancer.
Higher Faslodex Dose Improves Benefit in Advanced ER+ Breast Cancer
Postmenopausal women with locally advanced or metastatic estrogen-receptor positive breast cancer who recurred or progressed on prior endocrine therapy did better when taking 500 mg of fulvestrant (Faslodex), rather than 250 mg. Fulvestrant is an intramuscular injection.
The higher dose showed a significant 4.1-month improvement in overall survival (OS) when compared with the lower dose, from 22.3 months to 26.4 months. It also resulted in a 19% drop in the risk of death.
For the phase 3 CONFIRM trial, investigators enrolled 736 women and randomly assigned roughly 50% of them to receive 500 mg of fulvestrant on days 0, 14 (2 placebo injections), and 28, and 28 days thereafter. The other half received 250 mg every 28 days. When the analysis was shown to favor the higher dose, women who were in the 250 mg arm of the trial were permitted to cross over and receive 500 mg. The median age of the enrollees was 61.
The 500 mg dose of fulvestrant did not significantly increase toxicities. About 10% of the women taking the higher dose experienced at least one serious adverse event (SAE), compared with roughly 7% in the 250 mg arm. SAE’s were acute myocardial infarction, acute renal failure, cardiopulmonary failure, dyspnea (shortness of breath), and hypertension.
Angelo Di Leo, M.D., Ph.D., presented the final results of the CONFIRM trial at the symposium. He is head of the department of medical oncology at the Hospital of Prato, Instituto Toscano Tumori in Prato, Italy.
Targeted Compound Improves PFS in Advanced ER+ Breast Cancer
Women with postmenopausal advanced breast cancer who received a targeted agent along with the aromatase inhibitor letrozole (Femara) showed a meaningful improvement in median progression free survival (PFS), according to the results of a phase 2 trial.
The data showed that postmenopausal women who took the oral drug PD 0332991, or PD991 for short, had a significant, median PFS of 26.1 months compared with 7.5 months for women in the control arm.
The researchers enrolled 165 women in the trial. The enrollees had estrogen-receptor positive, HER2 negative metastatic breast cancer.
PFS was the primary endpoint. Secondary endpoints included response rate, overall survival, safety, and biomarker studies.
The response rate was 45% for the combined regimen and 31% for letrozole alone. The clinical benefit rate, which showed complete and partial responses, as well as stable disease, was 70% versus 44%, respectively.
In an attempt to determine meaningful biomarkers, the researchers also studied tumors that were amplified for CCND1 and/or had loss of p16. Both have sensitivity to PD991 in vitro. CCND1 is a gene that regulates cell cycle progression. It may contribute to tumorigenesis. The protein p16 relates to the ability of the body to suppress tumors.
Based on the promising data, the researchers plan to begin a phase 3 trial in 2013.
The results were reported by Richard S. Finn, M.D., associate professor of medicine at the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles.
Neoadjuvant Chemo May Provide Clues for mTNBC
Scientists are looking at the response of triple negative breast cancer (TNBC) tumors in the neoadjuvant setting to potentially identify cell abnormalities that can lead to treating TNBC in the adjuvant and metastatic settings.
In early stage breast cancer, neoadjuvant chemotherapy is administered prior to breast surgery and can result in either complete or partial shrinkage of the tumor.
The authors of this study genetically examined residual tumor tissue from 114 women after the patients completed neoadjuvant chemotherapy. They discovered that 90% of the samples had an abnormality in at least one of five cell pathways. The pathways have clinically actionable targets: DNA-repair targeting agents and inhibitors of PI3K/mTOR, RAF/MEK, cell cycle/miotic spindle, and RTK.
Research has already shown that not all TNBC’s are alike, and the results of this study suggest that women with metastatic disease could be grouped into clinical trials depending on the abnormalities of their tumor, in order to test pathway inhibitors.
Justin M. Balko, Pharm.D., Ph.D. presented the results of this study. He is with Vanderbilt-Ingram Cancer Center in Nashville, Tenn.