“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.’ “
“Pfizer Inc. PFE, +1.01% today announced that the Phase 3 PALOMA-3 trial for IBRANCE® (palbociclib) met its primary endpoint of demonstrating an improvement in progression-free survival (PFS) for the combination of IBRANCE plus fulvestrant compared with fulvestrant plus placebo in women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer following disease progression during or after endocrine therapy. The study was stopped early due to efficacy based on an assessment by an independent Data Monitoring Committee (DMC). These are the first randomized Phase 3 trial results for IBRANCE, a new anti-cancer medicine with the novel mechanism of cyclin-dependent kinase 4/6 (CDK 4/6) inhibition.
“ ‘The results of this trial are especially important because they help us understand the potential of IBRANCE to improve outcomes in patients with this difficult to treat cancer. We’re gratified to be able to stop the trial early and are engaging in discussions with health authorities regarding a regulatory path forward,’ said Dr. Mace Rothenberg, senior vice president of Clinical Development and Medical Affairs and chief medical officer for Pfizer Oncology.
“The adverse events observed with IBRANCE in combination with fulvestrant in PALOMA-3 were generally consistent with their respective known adverse event profiles. Detailed efficacy and safety results from PALOMA-3 will be submitted for presentation at the American Society of Clinical Oncology (ASCO) 2015 Annual Meeting.”
“Improved prognosis for women with estrogen receptor–positive breast cancer who experience a large reduction in mammographic density following the initiation of tamoxifen treatment extends to premenopausal as well as postmenopausal women, researchers reported in the Journal of the National Cancer Institute. While a previous analysis linked decline in mammographic density following initiation of tamoxifen with improved survival in postmenopausal women, this more recent evaluation of change also showed improved survival in premenopausal women ‘for whom tamoxifen is the primary anti-endocrine therapy,’ Nyante et al wrote.
“ ‘Mammographic density reflects the fibroglandular composition of the breast, and women with the highest levels have approximately four-fold higher breast cancer risk compared with women with the lowest density,’ the investigators noted. ‘Emerging evidence,’ they added, ‘indicates that density reductions specifically among tamoxifen users may predict treatment effectiveness in adjuvant and chemopreventative settings, which could have value for planning long-term treatment.’ ”
“Palbociclib, an investigational oral medication that works by blocking molecules responsible for cancer cell growth, is well tolerated and extends progression-free survival (PFS) in newly diagnosed, advanced breast cancer patients, including those whose disease has stopped responding to traditional endocrine treatments. Results of the phase II study, led by researchers in the Abramson Cancer Center and the Perelman School of Medicine at the University of Pennsylvania , were published this month in Clinical Cancer Research. Earlier phase I results by researchers at Penn Medicine contributed to the development of palbociclib, which was recently approved by the U.S. Food and Drug Administration (FDA) for metastatic breast cancer patients just beginning to undergo endocrine therapy.
” ‘The FDA approval has expanded treatments options for many metastatic breast cancer patients, but these new results are showing how effective the drug can also be for breast cancer patients who have already tried endocrine therapies and may be running out of options,’ said lead investigator Angela DeMichele, MD, MSCE , associate professor in the division of Hematology/Oncology and Epidemiology and co-leader of the Breast Cancer Research Program at the Abramson Cancer Center. ‘Combined with the promising results from other trials looking at the effectiveness of this drug, our results indicate that palbociclib can extend the duration of disease control and produce tumor shrinkage in patients with estrogen-receptor positive (ER+) breast cancer, without the debilitating side effects of chemotherapy.’ “
The gist: In October, the U.S. Food and Drug Administration (FDA)announced that it had granted Priority Review to new breast cancer drug palbociclib, meaning that it would speed its review process to get the drug to more patients sooner. However, as of January 2015, the FDA has not yet planned a meeting to evaluate the drug. The reason for the delay has not been announced. Palbociclib has shownpromise for postmenopausal women with advanced, ER-positive, HER2-negative breast cancer. If it is approved by the FDA, doctors across the U.S. will be able to prescribe palbociclib to these patients.
“The U.S. Food and Drug Administration isn’t planning an advisory committee meeting at this time to evaluate Pfizer Inc.’s experimental breast-cancer treatment, despite the drug having received priority-review status in October, the company said Thursday.
“Pfizer didn’t provide reasons for the delay, but said it continues to talk with the FDA about the application for palbociclib, also known by the brand name Ibrance.
“An FDA spokesperson wasn’t immediately available to respond.
“The drug is one of many experimental therapies that targets certain proteins in the body known as CDKs. Cancer hijacks these proteins to help tumor cells grow. Recent studies suggest that stopping these proteins can help stall cancer.”