“A dual approach to overcoming resistance to endocrine therapy in patients with advanced hormone receptor (HR)–positive breast cancer is under investigation in a phase III trial that adds the novel drug entinostat to standard exemestane therapy after disease progression.
“The combination has generated excitement in the oncology drug development field after demonstrating an 8-month overall survival (OS) benefit over exemestane alone in the phase II ENCORE 301 study. Those positive results prompted the FDA to grant a breakthrough therapy designation to entinostat in this setting.”
“Plasma analysis of ESR1 mutations may aid in the identification of appropriate endocrine therapy for patients with advanced breast cancer who progress after treatment with aromatase inhibitors, according to study results published in Journal of Clinical Oncology.
“ ‘Although diverse mechanisms of resistance to endocrine therapy have been described, recent evidence identified mutations in the ER gene (ESR1),’ Nicholas C. Turner, MA, MRCP, PhD, consultant medical oncologist at The Royal Marsden NHS Foundation Trust and team leader at the Breakthrough Breast Cancer Research Centre at Institute for Cancer Research, London, and colleagues wrote. ‘ESR1 mutations occur rarely in primary breast cancer, but have a high prevalence in advanced breast cancers previously treated with aromatase inhibitors, implying evolution through selective treatment pressure.’ ”
Do you have questions about this story? Let us know in a comment below. If you’re wondering whether this story applies to your own cancer case or a loved one’s, we invite you to use our Ask Cancer Commons service.
“Roughly 5 years ago, a study demonstrated that neoadjuvant endocrine therapy increases the rates of breast conservation surgery in patients with breast cancer as a result of the downstaging of disease.
“Now, an analysis of roughly 80,000 women with breast cancer in the United States shows that this study has done little to increase the use of this treatment modality.
” ‘Neoadjuvant endocrine therapy use has increased since the publication of Z1031 [the American College of Surgeons Oncology Group (ACOSOG) Z1031 study]. However, the overall rate of neoadjuvant endocrine therapy use is low, at 3.2%,’ said Akiko Chiba, MD, a breast surgery fellow at the Mayo Clinic, Rochester, Minnesota, who presented the study at the Society of Surgical Oncology (SSO) 2016 Cancer Symposium.”
“The Food and Drug Administration (FDA) has granted an expanded indication for the cyclin-dependent kinase 4/6 inhibitor palbociclib (Ibrance). The drug is now approved for use in combination with fulvestrant in women with hormone receptor (HR)-positive, HER2-negative advanced or metastatic breast cancer whose disease progressed following endocrine therapy.
“Palbociclib was initially approved in February 2015 for the treatment of estrogen receptor–positive, HER2-negative metastatic breast cancer, in women who had not yet received endocrine therapy. The new approval was granted under the FDA’s breakthrough therapy designation.
“The additional indication for palbociclib is based on results from the PALOMA-3 trial, which was stopped early in April 2015 after an interim analysis showed benefit in combination with fulvestrant when compared to fulvestrant and placebo.”
“An American Society of Clinical Oncology (ASCO) expert panel issued an updated guideline recommending that higher-risk premenopausal women with estrogen receptor (ER)-positive breast cancer receive ovarian suppression in addition to adjuvant endocrine therapy. Lower-risk patients, however, should not receive ovarian suppression.
“ ‘In the past year, randomized trials with robust methodological designs have analyzed the effect of ovarian suppression among premenopausal women with ER-positive breast cancers treated with tamoxifen,’ wrote the panel, led by ASCO expert Harold J. Burstein, MD, PhD, of Dana-Farber Cancer Institute in Boston. In the past, studies of this therapy have suffered from problems such as selection criteria confounding.
“The guideline update is based on four randomized controlled trials. These include the Eastern Cooperative Oncology Group 3193 (E-3193) trial, the Suppression of Ovarian Function Trial (SOFT), the Tamoxifen and Exemestane Trial (TEXT), and the Austrian Breast Cancer Study Group (ABCSG)-12 trial. Overall, the studies did not find a significant difference with regard to overall survival between tamoxifen alone, tamoxifen plus ovarian suppression, or aromatase inhibitors (AIs) plus ovarian suppression. The guideline update was published in the Journal of Clinical Oncology.”
“Pfizer Inc. (NYSE:PFE) today announced that the U.S. Food and Drug Administration (FDA) has accepted for filing and granted Priority Review for a supplemental New Drug Application (sNDA) for Pfizer’s breast cancer medication, IBRANCE® (palbociclib). If approved, the sNDA would expand the approved use of IBRANCE to reflect findings from the Phase 3 PALOMA-3 trial, which evaluated IBRANCE in combination with fulvestrant versus fulvestrant plus placebo in women with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+, HER2-) metastatic breast cancer, regardless of menopausal status, whose disease progressed after endocrine therapy, including those with and without prior treatment for their metastatic disease. The Prescription Drug User Fee Act (PDUFA) goal date for a decision by the FDA is April 2016.”
“The new investigational estrogen receptor (ER) degrader GDC-0810 was safe and tolerable in postmenopausal women with advanced ER-positive breast cancer, and a subset of the women, all of whom were previously treated with standard endocrine therapy, gained clinical benefit from the drug, according to data from a first-in-human phase I/IIa clinical trial presented here at the AACR Annual Meeting 2015, April 18-22.
” ‘Most breast cancers diagnosed in the United States are ER-positive, and their growth is fueled by the hormone estrogen,’ said Maura N. Dickler, MD, associate member of the Breast Medicine Service at Memorial Sloan Kettering Cancer Center and Weill Medical College of Cornell University in New York. ‘Resistance to currently available therapies targeting estrogen and the estrogen receptor causes morbidity and mortality for women with metastatic ER-positive breast cancer and new therapies that have activity against tumors resistant to currently available treatments are urgently needed.
” ‘The phase I dose-escalation portion of the study enrolled heavily pretreated patients, and the observed antitumor activity is promising for GDC-0810, which is demonstrating clinical benefit in these patients who have developed resistance to other endocrine therapies for ER-positive breast cancer patients,’ continued Dickler. ‘The phase IIa dose-expansion portion of the study is ongoing. It is evaluating GDC-0810 efficacy in more defined patient subpopulations and will provide more information about how effective this estrogen receptor degrader is.’ “
“The addition of bevacizumab did not prolong progression-free survival (PFS) or overall survival in postmenopausal women with HER2-negative, hormone receptor–positive advanced breast cancer treated with first-line endocrine therapy.
“The results of the Letrozole/Fulvestrant and Avastin (LEA) study were published in the Journal of Clinical Oncology.
“The median PFS was 14.4 months in the endocrine therapy arm and 19.3 months in the endocrine therapy plus bevacizumab arm (hazard ratio = 0.83; P = .126). The overall response rate was 22% and 41% in the control arm and the bevacizumab arm (P < .001). The duration of response was 13.3 months in the control arm compared with 17.6 months in the bevacizumab arm (P = .434). The time to treatment failure and overall survival were similar in both treatment arms.
“Study author Miguel Martín, MD, PhD, of Complutense University of Madrid told Cancer Network that there was a trend towards a better PFS in favor of the combination of bevacizumab and hormones. ‘Therefore, we cannot simply conclude that bevacizumab is ineffective in this setting.’ “
The gist: A clinical trial compared postmenopausal breast cancer patients who took tamoxifen after surgery with patients who took tamoxifen plus the drug anastrozole. They researchers found that, after three years, more women with lobular breast cancer who took anastrozole were alive than those who took only tamoxifen. These results suggest that anastrozole may benefit postmenopausal women with lobular breast cancer.
“The survival benefit postmenopausal patients with breast cancer derive from anastrozole vs. tamoxifen varies considerably by histology, according to an analysis of phase 3 study results presented at the San Antonio Breast Cancer Symposium.
“Researchers suggested the finding may help refine adjuvant endocrine treatment decisions.
“Several prior studies showed aromatase inhibitors improved outcomes among postmenopausal patients with breast cancer compared with tamoxifen monotherapy. A meta-analysis by Forbes and colleagues, which included data on 11,798 patients included in randomized trials that compared 5 years of tamoxifen vs. a sequence of tamoxifen followed by aromatase inhibitors, showed patients assigned aromatase inhibitors demonstrated a significant reduction in recurrence (RR=0.84; 95% CI, 0.73-0.97). Researchers also observed significantly fewer deaths in the aromatase inhibitor group (RR=0.84; 0.73-0.97)…
“ ‘In summary, among all patients with lobular cancer, anastrozole was associated with a significant reduction in OS events compared to tamoxifen,’ Knauer said. ‘However, anastrozole efficacy was strongly depending on histology and intrinsic subtype of breast cancer.’ ”