Study Shows that Prosigna Test Influences Docs' Chemo Recommendations for Women with ER+, Node-Negative Breast Cancer

The gist: A recent study showed that a test called Prosigna affects whether oncologists recommend chemotherapy to women with estrogen receptor (ER)-positive, node-negative breast cancer.

“NanoString Technologies, Inc. (NASDAQ:NSTG), a provider of life science tools for translational research and molecular diagnostic products, today announced that the results of the first Prosigna® Assay decision impact study presented at the 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium (SABCS) showed that the use of the test significantly changed oncologists’ treatment recommendations. Conducted in collaboration with Grupo Español de Investigación del Cáncer de Mama (GEICAM), a Spanish breast cancer research group, this prospective study of the Prosigna Assay and its impact on the treatment of women with Estrogen Receptor-Positive (ER+), HER2-negative, node-negative breast cancer showed that the use of the test informed the oncologists’ recommendation whether or not to treat with adjuvant chemotherapy in addition to adjuvant endocrine therapy.

“ ‘We are very pleased to see that in this study, Prosigna was used by oncologists to make more informed decisions regarding the administration of adjuvant chemotherapy for early-stage breast cancer patients,’ stated Brad Gray, President and Chief Executive Officer of NanoString. ‘Also, we were pleased to recapitulate the results of our earlier analytical validation study, which showed that Prosigna can be run at multiple sites and generate high-quality, consistent results…’ ”

“Overall, the investigators concluded that Prosigna can be reliably performed in hospital laboratories to provide useful information beyond standard clinicopathological variables that oncologists can use to inform adjuvant treatment recommendations in clinical practice, and that this study provides additional evidence that Prosigna has analytical validity and clinical utility in real-world settings.”


Adding Pictilisib to Anastrozole Treatment Might Improve Responses for Patients with Early-Stage, ER+, HER2-, Luminal B Breast Cancer

The gist: The drug pictilisib might improve response to treatment with the drug anastrozole for patients with early-stage, ER-positive, HER2-negative, luminal B breast cancer. In a clinical trial, patients who took pictilisib with anastrozole had better responses than patients who took anastrozole alone.

“The addition of pictilisib to anastrozole improved anti-proliferative response through the reduction of Ki67 in patients with early-stage breast cancer and particularly among those with luminal B tumors, according to study results presented at the San Antonio Breast Cancer Symposium…

“Schmid and colleagues evaluated data from 73 post-menopausal women with newly diagnosed breast cancer. All women had ER-positive, HER-2–negative disease. Fifty-three percent of the women had luminal A tumors, and 47% had luminal B tumors.

“Researchers randomly assigned patients 2:1 to the PI3K inhibitor pictilisib (GCD-0941, Genentech) plus 1 mg anastrozole (n=50) or anastrozole alone (n=23) for 2 weeks prior to surgery. The dose of pictilisib was reduced from 340 mg to 260 mg due to a concern for side effects demonstrated on other studies…

“ ‘The data presented show that the addition of the PI3 kinase inhibitor pictilisib significantly increases the anti-proliferative response of anastrozole in ER-positive breast cancer,’ Schmid said. ‘Subsequent analyses suggest increased benefit of pictilisib for patients with luminal B and highly proliferative tumors.’ ”


Weekly Paclitaxel or Docetaxel Every 3 Weeks Improves Survival in Breast Cancer

The gist: A different treatment schedule after surgery might increase survival and time without cancer worsening for women with axillary node-negative or high-risk node-negative breast cancer. A clinical trial found that these women might benefit from taking the drug paclitaxel once per week or docetaxel once every three weeks, instead of paclitaxel once every three weeks. The same trial found that women with triple negative breast cancer (TNBC) also benefit from weekly paclitaxel. But docetaxel once every three weeks showed better results for women with ER-positive, HER2–negative breast cancer.

“Women with axillary node-negative or high-risk node-negative breast cancer achieved prolonged DFS and marginally improved OS when they received adjuvant paclitaxel every week or docetaxel every 3 weeks compared with paclitaxel every 3 weeks, according to phase 3 study results presented at the San Antonio Breast Cancer Symposium.

“Further, weekly paclitaxel extended DFS and OS in women with triple-negative breast cancer, whereas docetaxel administered every 3 weeks improved DFS in women with ER-positive, HER-2–negative disease.

“Joseph A. Sparano, MD, professor of medicine and women’s health at Albert Einstein College of Medicine, and colleagues evaluated various regimens in 4,954 women with axillary node-positive or high-risk node-negative breast cancer. Previously released results, based on a median 5.3 years of follow-up, showed those who received adjuvant weekly paclitaxel (HR=0.73; P=.0006) or docetaxel every 3 weeks (HR=0.77; P=.02) demonstrated longer DFS than women who received paclitaxel every 3 weeks.

“The current analysis occurred after a median 12.1 years of follow-up. The numbers of DFS events (1639 vs. 1048) and deaths (1283 vs. 686) in the current analysis vs. the previous report were substantially higher.”


Promising Drug Staves Off Cancer Worsening in Hormone Receptor-Positive Breast Cancer Patients

The gist: A drug called palbociclib may increase the amount of time that passes without cancer worsening for patients with advanced, estrogen receptor (ER)-positive, HER2-negative breast cancer. In a clinical trial, some patients were treated with palbociclib along with letrozole, and some were treated with letrozole alone. Patients who took both drugs went for twice as long without their cancer worsening than patients who took only letrozole. Learn more about palbociclib in breast cancer.

“In a groundbreaking study that offers new hope for women with advanced breast cancer, researchers from UCLA’s Jonsson Comprehensive Cancer Center have published final clinical trial results that showed the amount of time patients were on treatment without their cancer worsening (called progression-free survival) was effectively doubled in women with advanced breast cancer who took the experimental drug palbociclib.

“An investigational drug discovered and being developed by Pfizer Inc., palbociclib targets a key family of proteins (CDK4/6) responsible for cell growth by preventing them from dividing. Results of the multi-year phase 2 study showed a significant increase in PFS for patients with advanced breast cancer that was estrogen receptor positive (ER+), HER2-negative (HER2-), who were given a combination of the standard anti-estrogen treatment, letrozole, and palbociclib compared to letrozole alone.

” ‘We’re essentially putting the brakes on cell proliferation and causing these tumor cells to stop growing,’ said Dr. Richard Finn, associate professor of medicine at UCLA and lead author of the study.

“The study was published online ahead of print in the journal The Lancet Oncology.”


SABCS 2014: PI3K Inhibition With Pictilisib in Hormone Receptor–Positive Breast Cancer Not Ready for Prime Time

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.”


Novel Approach for Estrogen-Receptor-Positive Breast Cancer Reported

The gist: Drugs called gamma secretase inhibitors (GSI) are being explored as a potential way to overcome resistance to endocrine therapy drugs (like tamoxifen or letrozole) for women with estrogen-receptor-positive (ER+) breast cancer. A GSI drug called MK-0752 was recently given to patients in a clinical trial. The researchers found 18 tumor genes that could be used to predict how well GSI might work for a given patient. A larger study will explore the gene “signature” and measure just how effective GSI drugs are for breast cancer patients.

“Loyola researchers and collaborators have reported promising results from a novel therapeutic approach for women with estrogen-receptor-positive breast cancer.

“The new approach, a new drug class called gamma secretase inhibitors (GSI), specifically inhibits Notch and shuts down critical genes and cancer cells responsible for tumor growth.

“Kathy Albain, MD, FACP, who led the study, will present findings Dec. 11 during the 2014 San Antonio Breast Cancer Symposium.

“Existing cancer drugs are effective in killing mature breast cancer cells. But a handful of immature breast cancer stem cells are resistant to such drugs. They survive and are responsible for tumor growth and progression. Resistance to standard therapy is a major cause of death in women with estrogen-receptor-positive breast cancer. Approximately 75 percent of breast cancers are estrogen-receptor positive…

“Researchers are planning a larger, phase II study to evaluate the efficacy of the GSI class of drugs added to endocrine therapy versus endocrine therapy alone. This study also will determine how well the 18 gene “signature” will predict who responds to therapy.

” ‘This is an exciting new strategy to overcome resistance to a very common class of drugs (tamoxifen, letrozole), so it is our hope that in the future a vast number of patients with estrogen-receptor-positive breast cancer could benefit,’ Dr. Albain said.”


New Drug Combination for Advanced Breast Cancer Delays Disease Progression

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.”


Subsidies Help Breast Cancer Patients Adhere to Hormone Therapy

“A federal prescription-subsidy program for low-income women on Medicare significantly improved their adherence to hormone therapy to prevent the recurrence of breast cancer after surgery.

” ‘Our findings suggest that out-of-pocket costs are a significant barrier’ to women complying with hormone therapy, said Dr. Alana Biggers, assistant professor of clinical medicine at the University of Illinois at Chicago College of Medicine, and lead investigator on the study. Programs that lower these costs can ‘improve adherence—and, hopefully, breast cancer outcomes—for low-income women,’ she said. Biggers presented the results of the study at an Oct. 14 press conference in advance of the American Society for Clinical Oncology Quality Care Symposium in Boston.

“Breast cancer is a leading cause of cancer-related deaths for women of all races, but survival rates differ by race and socioeconomic status, with African American women and women of low income having higher rates of death.”


Pfizer Announces FDA Acceptance of Palbociclib New Drug Application with Priority Review

The gist: In the U.S., a drug must be approved by the U.S. Food and Drug Administration (FDA) in order for it to be prescribed to patients with specific diseases. Particularly promising drugs might be granted Priority Review, meaning that the FDA agrees to work with the drug manufacturer to accelerate the approval process. The FDA recently granted priority review to a drug meant to treat certain breast cancer patients. The drug is called palbociclib. It is meant to be combined with another drug called letrozole as a treatment for “postmenopausal women with estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer who have not received previous systemic treatment for their advanced disease.”  The FDA’s decision was based on promising results for the treatment in a clinical trial that tested it in volunteer patients. People who are interested in getting the treatment before it is approved can look into participating in Pfizer’s expanded access trial.

“Pfizer Inc. today announced the New Drug Application (NDA) for palbociclib has been accepted for filing and granted Priority Review by the United States Food and Drug Administration (FDA). This NDA requests FDA approval of palbociclib, in combination with letrozole, as a first-line treatment for postmenopausal women with estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer who have not received previous systemic treatment for their advanced disease. The submission is based on the final results of PALOMA-1, a randomized, Phase 2 trial comparing palbociclib plus letrozole versus letrozole alone in this population of patients.

“The FDA’s Priority Review status accelerates the review time from 10 months to a goal of six months from the day of acceptance of filing and is given to drugs that may offer major advances in treatment or may provide a treatment where no adequate therapy exists. The Prescription Drug User Fee Act (PDUFA) goal date for a decision by the FDA is April 13, 2015.

“Palbociclib received Breakthrough Therapy designation from the FDA in April 2013, for the first-line systemic treatment of women with advanced or metastatic ER+, HER2- breast cancer.

“ ‘If approved as a first-line therapy in combination with letrozole, palbociclib will be an important new option for the thousands of women in the U.S. who are living with metastatic breast cancer,’ said Garry Nicholson, president, Pfizer Oncology. ‘We look forward to continuing to work closely with the FDA through the review process.’

“Pfizer recently announced the initiation of a multi-center, open-label expanded access program (EAP) in the United States for palbociclib. Through the program, palbociclib is available to post-menopausal women with hormone receptor-positive (HR+), HER2- advanced breast cancer who are eligible for letrozole therapy and for whom enrolling in other palbociclib clinical trials is not an option. Healthcare professionals and patients can learn more about the palbociclib EAP by visiting www.clinicaltrials.gov (trial number: NCT02142868).”