“Combining the new breast cancer drug palbociclib with paclitaxel (Taxol) shrank tumors in nearly half of patient with estrogen-receptor (ER) positive breast cancer, according to new research from the Perelman School of Medicine at the University of Pennsylvania. The results will be presented Saturday at the 2015 San Antonio Breast Cancer Symposium. A second study provides new clues to how breast cancer develops resistance to the palbociclib, a common occurrence among many patients who take the drug.
” ‘Results of the first study found that palbociclib and paclitaxel can be safely combined on an alternating dosing schedule,’ said Angela DeMichele, MD, MSCE, the Alan and Jill Miller Associate Professor in Breast Cancer Excellence in Penn’s Abramson Cancer Center, and senior author on the study. ‘The high response rate we saw suggests this combination may hold benefits for patients over paclitaxel alone. Based on these results, a larger clinical trial to determine the benefits is warranted.’ “
Women diagnosed with localized breast cancer face difficult decisions with their doctors. What kind of neoadjuvant (before surgery) treatment to choose? Should chemotherapy follow surgery? Based on the subtype of breast cancer, should specific chemotherapy drugs be used? Continue reading…
“As reported in the Journal of Clinical Oncology, Turnbull et al identified a four-gene predictive model of response to aromatase inhibitor therapy that was highly predictive of response on the basis of pretreatment and 2-week on-treatment measurements. The classifier was a significant predictor of recurrence-free and breast cancer–specific survival.
“In the study, 89 postmenopausal women who had estrogen receptor-alpha–positive breast cancer and were receiving neoadjuvant letrozole underwent biopsy for transcript profiling before letrozole treatment and at 2 weeks and 3 months after starting treatment. Dynamic clinical response was assessed by three-dimensional ultrasound measurements.
“Molecular response to letrozole was characterized, and a four-gene classifier of clinical response was identified. The classifier consisted of levels of two genes before treatment (IL6ST, associated with immune signaling, and NGFRAP1, associated with apoptosis) and the levels of two proliferation genes (ASPM and MCM4) after 2 weeks of therapy.”
Earlier this year, a new treatment option was added to the arsenal for ER-positive breast cancer in postmenopausal women when the U.S. Food and Drug Administration (FDA) approved the combination of letrozole (Femara) and palbociclib (Ibrance). Continue reading…
“Kari Wisinski, MD, medical oncologist with University Of Wisconsin Health and the University of Wisconsin Carbone Cancer Center, discusses the use of palbociclib for patients with ER-positive and HER2-negative breast cancer.
“Currently there is not a specific patient population that has been identified as ideal for palbociclib, says Wisinski.
“The PALOMA-3 trial demonstrated that palbociclib plus fulvestrant compared with fulvestrant plus placebo improved progression-free survival (PFS) in women with ER-positive and HER2-negative metastatic breast cancer following disease progression. Based on these results, the drug gained accelerated approval in February 2015.
“The PFS data is impressive, says Wisinski, and the swift approval of the drug has benefited patients who need to delay chemotherapy while maintaining PFS.”
“Patricia Ganz, MD, medical oncologist at the Jonsson Comprehensive Cancer Center at UCLA, discusses an education session at the ASCO Annual Meeting that examined reasons why chemoprevention is underutilized in patients with breast cancer.
“ ‘In spite of high-level evidence from multiple randomized clinical trials that show substantial reduction in the risk of getting breast cancer — especially ER-positive breast cancer — very few women are identified as being at high risk,’ Ganz told HemOnc Today. ‘And even of those who are identified, the recommendation and the use of … tamoxifen and raloxifene is very infrequent.’ ”
“A Phase III trial of Pfizer Inc’s Ibrance showed that, in combination with hormone therapy, the drug more than doubled the duration of disease control for women with the most common type of breast cancer.
“At the time of an interim analysis, patients given Ibrance and AstraZeneca Plc’s Faslodex (fulvestrant), a widely used treatment to block estrogen, lived an average of 9.2 months before their cancer worsened. This compared with 3.8 months for patients treated with Faslodex and a placebo.
“The trial, presented in Chicago at a meeting of the American Society of Clinical Oncology, enrolled 521 patients whose breast cancer was classified as estrogen-receptor positive, human epidermal growth factor receptor 2-negative. This category accounts for about 75 percent of all breast cancers.
“Ibrance, or palbociclib, was given conditional approval by the U.S. Food and Drug Administration in February for such patients, but only those who had not previously been treated for advanced breast cancer.”
“The dual mTOR inhibitor AZD2014, when combined with the hormonal therapy fulvestrant (Faslodex), was found to be safe in patients with advanced estrogen receptor–positive breast cancer, and some of them experienced clinical benefit from the drug combination, according to phase I clinical trial data presented at the AACR Annual Meeting 2015, April 18 to 22 in Philadelphia (Abstract CT233).
“ ‘Patients with estrogen receptor–positive breast cancer respond to hormonal therapy, but over time, some eventually develop resistance to treatment. Their tumors become dependent on a cell-signaling pathway called the mTOR pathway for survival,’ said Manish R. Patel, MD, Associate Director of Drug Development for Sarah Cannon Research Institute and Director of Drug Development at the Florida Cancer Specialists and Research Institute.
“ ‘We are testing whether combining the hormonal therapy fulvestrant with the dual mTOR inhibitor AZD2014 can help overcome this resistance. AZD2014 is a new anticancer therapy and represents a potential improvement compared with other drugs that have similar mechanisms of action,’ Dr. Patel added.
“ ‘In this trial, we tested two dosing schedules of AZD2014: continuous dosing, in which the drug is given every day, and intermittent dosing, in which the drug is given only 2 days of each week,’ Dr. Patel explained. ‘We compared the side-effect profiles of the two dosing schedules. The response of individual patients to treatment was also monitored.’ “
“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.’ “