Pfizer Announces FDA Acceptance of IBRANCE® (palbociclib) Supplemental New Drug Application with Priority Review in HR+, HER2- Metastatic Breast Cancer

“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.”


Phase III BELLE-2 Trial Meets Primary Endpoint of Progression-free Survival

“Among women with locally advanced or metastatic hormone receptor-positive breast cancer that was resistant to hormone therapy, those who had mutated PIK3CA detected in their blood benefited from a combination of the investigational PI3K inhibitor buparlisib and fulvestrant, according to data from the phase III BELLE-2 trial presented at the 2015 San Antonio Breast Cancer Symposium, held Dec. 8–12.

“ ‘BELLE-2 is a randomized, phase III clinical trial designed to assess the efficacy of the investigational PI3K inhibitor buparlisib in combination with fulvestrant in breast cancer patients whose tumors no longer respond to aromatase inhibitors,’ said José Baselga, MD, PhD, physician-in-chief and chief medical officer at Memorial Sloan Kettering Cancer Center in New York.”


FDA Grants Priority Review to Ibrance for New Indication in Advanced Breast Cancer

“The FDA granted priority review to a supplemental new drug application for the breast cancer medication palbociclib.

“Palbociclib (Ibrance, Pfizer) — an oral agent that inhibits cyclin-dependent kinases (CDK) 4 and 6 — already is approved for use in combination with letrozole for treatment of postmenopausal women with ER-positive, HER-2–negative advanced breast cancer as initial endocrine-based therapy for metastatic disease.

“The supplemental application requests that the approval be expanded to allow for use of palbociclib in combination with fulvestrant in women with hormone receptor-positive, HER-2–negative metastatic breast cancer that progressed after endocrine therapy. The application requests approval in this setting regardless of patients’ menopausal status or receipt of prior treatment for metastatic disease.”


Phase 1 Results Point to Larger Trial of Enzalutamide and Fulvestrant in Breast Cancer

“Results of a multicenter phase 1 clinical trial presented today at the 2015 San Antonio Breast Cancer Symposium show that the anti-androgen agent enzalutamide is active and well-tolerated alone and with fulvestrant in patients with advanced breast cancer. The study takes another important step toward larger clinical trials targeting androgen receptors in breast cancer.

” ‘We’ve known for years that prostate cancer is driven by androgens and now it’s increasingly clear that androgens and androgen receptors can influence many breast cancers as well. AR is actually even more prevalent in breast cancer than estrogen or progesterone receptors. Targeting androgen receptors in breast cancer gives us a new way to attack the disease,’ says Jennifer Richer, PhD, investigator at the University of Colorado Cancer Center. Results represent collaboration with CU Cancer Center clinical collaborator Anthony Elias, MD, Memorial Sloan Kettering, Medivation, Inc. and Astellas Pharma Global Development.”


Palbociclib's Role in Endocrine-Resistant Breast Cancer

“Palbociclib (Ibrance, Pfizer), the first CDK4/6 inhibitor to be approved for the treatment of breast cancer, has been welcomed by experts for its role in improving outcomes in patients with endocrine-resistant breast cancer.

“The drug should a significant improvement in progression-free survival (PFS) when it was added to fulvestrant (Faslodex, AstraZeneca) in the phase 3 PALOMA 3 trial, as reported recently by Medscape Medical News. The addition of palbociclib to fulvestrant increased median PFS to 9.2 months in patients with estrogen receptor (ER)–positive/HER2-negative endocrine-resistant breast cancer compared with 3.8 months in the placebo-fulvestrant group (P < .001).

“The overall survival data are still immature.

“The full results have now been published in print in the July 16 issue of the New England Journal of Medicine.


Top Takeaways from ASCO: Breast Cancer

“Physicians managing patients with various breast cancer diagnoses left ASCO 2015 with new data to consider when making decisions every day – some practice-changing, others potentially so.

“Key opinion leaders offer their views on positive results from trials investigating an adjunct endocrine therapy, an aromatase inhibitor as an option to tamoxifen, a novel chemotherapy and bisphosphonates.

“Nicholas C. Turner, MD, PhD, a consultant medical oncologist at the Royal Marsden and a team leader at the Institute of Cancer Research in London, and colleagues assessed the safety and efficacy of combining palbociclib (Ibrance, Pfizer), an oral agent that blocks cyclin dependent kinases 4 and 6, with fulvestrant (Faslodex, AstraZeneca) in women with hormone receptor-positive, HER-2–negative advanced breast cancer who had progressed on prior endocrine therapy.

“ ‘The palbociclib data with fulvestrant builds on this whole concept of partnering endocrine therapy with another agent,’ William J. Gradishar, MD, FACP, professor of medicine in the division of hematology and medical oncology, Northwestern University Feinberg School of Medicine, and breast cancer section editor for HemOnc Today, told Healio.com.”


ASCO Highlight: Another Treatment Option for ER-Positive Breast Cancer


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…


Video: Dr. Kari Wisinski on Palbociclib for Metastatic Breast Cancer

“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.”


Combination of a Dual mTOR Inhibitor and Fulvestrant Tested in ER+ Metastatic 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.’ “