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.’ “


Ibrance Trial Stopped Early Because of Strong Evidence of Drug's Efficacy in Metastatic ER+ HER2- Breast Cancer

“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.”


Adding Bevacizumab to Endocrine Therapy No Help in Advanced Breast Cancer

“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.’ “


Treatment with Fulvestrant Improved Survival Over Anastrozole in Untreated, Advanced, HR+ Breast Cancer

The gist: A clinical trial with volunteer patients found that a drug called fulvestrant outperformed the drug anastrozole for women with advanced, hormone receptor-positive breast cancer. None of the women had received any other treatment for their cancer. “Patients assigned fulvestrant survived a median of 54.1 months compared with 48.4 months for anastrozole.”

“Fulvestrant 500 mg significantly improved overall survival compared with anastrozole, among women with treatment-naive, advanced, hormone receptor-positive breast cancer, according to data from the phase II FIRST trial presented at the 2014 San Antonio Breast Cancer Symposium (SABCS).

“ ‘This is now the second randomized controlled trial where fulvestrant 500 mg has shown a time-to-progression and survival advantage over the control arm,” said study presenter John Robertson, MD, professor of surgery, University of Nottingham, Royal Derby Hospital, United Kingdom.

“The phase III CONFIRM study found fulvestrant 500 mg to have a survival advantage over anastrozole in the second-line setting.

“According to Robertson, fulvestrant was originally developed in a 250 mg dosage. However, early trials of fulvestrant 250 mg in the first and second line showed only equivalence to anastrozole and similarity to tamoxifen. However, when it was decided to double the dose, and the CONFIRM study showed a survival advantage for fulvestrant 500 mg, the researchers decided to also look at outcomes with the higher dose in the first-line setting.”