“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.’ “
“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.”
“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 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.”
The gist: Researchers are hoping a treatment approach called ‘PI3K inhibition’ might improve outcomes for people with hormone receptor-positive breast cancer. But it’s unclear whether the approach will be successful, and a recent attempt did not give stellar results. In a clinical trial, researchers gave patients the PI3K inhibitor drug pictilisib along with the drug fulvestrant (Faslodex). It did not significantly lengthen the amount of time patients went without their cancer worsening. But later analysis showed that it did stave off cancer getting worse in certain patients: women whose breast cancer is both estrogen receptor-positive (ER+) and progesterone receptor–positive (PR+). Further research is needed to see if any PI3K drugs are particularly effective. For more information, click through to the full article and see this other article from Cancer Network.
“Interest is high in studying the PI3K pathway in hormone receptor–positive breast cancer, but it is not clear which of the PI3K inhibitors under development—if any—will be a ‘home run.’
“Adding the pan-class I selective PI3K inhibitor pictilisib to fulvestrant (Faslodex) did not significantly improve progression-free survival in women with estrogen receptor–positive breast cancer, but in an exploratory analysis of the trial, progression-free survival was significantly extended in women with both estrogen receptor–positive and progesterone receptor–positive breast cancer. The findings were presented at the 2014 San Antonio Breast Cancer Symposium (Abstract S2-02).
“ ‘When we considered only women with breast cancer positive for both estrogen receptor and progesterone receptor, adding pictilisib resulted in a significant doubling of progression-free survival in an exploratory analysis. We plan to investigate whether the benefit of pictilisib for women with estrogen receptor-/progesterone receptor–positive breast cancer holds true in an additional cohort of patients within this study,’ stated lead author Ian Krop, MD, Director of Clinical Research for the Breast Oncology Program at the Dana-Farber Cancer Institute, Boston.”
The gist: A new treatment that combines the drugs bortezomib and fulvestrant has shown promise in treating post-menopausal women with metastatic hormone receptor-positive breast cancer whose disease worsened after being treated with drugs called aromatase inhibitors. The combo treatment was tested in 118 patients in a clinical trial. It doubled the number of patients still alive after 12 months, and it lowered the chance of patients’ cancer worsening. Further studies will continue to measure the effectiveness of the treatment.
“A new combination of cancer drugs delayed disease progression for patients with hormone-receptor-positive metastatic breast cancer, according to a multi-center phase II trial. The findings of the randomized study (S6-03) were presented at the 2014 San Antonio Breast Cancer Symposium, held Dec. 6-9, by Kerin Adelson, M.D., assistant professor of medical oncology at Yale Cancer Center and chief quality officer at Smilow Cancer Hospital at Yale-New Haven.
“The trial enrolled 118 post-menopausal women with metastatic hormone-receptor-positive breast cancer whose cancer continued to progress after being treated with an aromatase inhibitor. The study, based on work done by Doris Germain of Mt. Sinai Hospital, found that the combination of the drugs bortezomib and fulvestrant—versus fulvestrant alone—doubled the rate of survival at 12 months and reduced the chance of cancer progression overall.
“Bortezomib, used most commonly in treating multiple myeloma, is a proteasome inhibitor that prevents cancer cells from clearing toxic material. Fulvestrant causes clumping of the estrogen-receptor protein. When bortezomib blocks the ability of the cell to clear these protein clumps, they grow larger and become toxic to the cancer cells. This, in turn, amplifies the effectiveness of fulvestrant, a drug commonly used in this subset of patients.
“The drug combination doubled the number of patients whose cancer had not progressed after one year from 14% to 28%, according to Adelson.”