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 (trial number: NCT02142868).”

Breast Conserving Therapy Shows Survival Benefit Compared to Mastectomy in Early-Stage Patients

Editor’s note: Women with early-stage breast cancer have surgery to remove their tumors. They can choose between a mastectomy to remove the entire breast or a lumpectomy to remove the diseased part of the breast (breast conserving therapy, or BCT). Until now, it was thought that a mastectomy and BCT had similar results in terms of long-term survival for a patient. But a new study shows that BCT offers better survival for women who are PR-positive or ER-positive. Further studies are needed to figure out why. The researchers speculate it may have to do with the radiation treatment usually given just after BCT to keep the cancer from returning. Unfortunately, there appear to be socioeconomic barriers to receiving BCT instead of a mastectomy.

“When factoring in what is now known about breast cancer biology and heterogeneity, breast conserving therapy (BCT) may offer a greater survival benefit over mastectomy to women with early stage, hormone-receptor positive disease, according to research from The University of Texas MD Anderson Cancer Center.

“The study findings defy the conventional belief that the two treatment interventions offer equal survival, and show the need to revisit some standards of breast cancer practice in the modern era.

“The research was presented at the 2014 Breast Cancer Symposium by Catherine Parker, MD, formerly a fellow at MD Anderson, now at the University of Alabama Birmingham.”

Gene Marker may Predict Breast Cancer Response to Tamoxifen

The gist: Oncologists can sometimes check a patient’s tumor for specific genetic mutations that indicate how well different treatment options might work. Researchers recently discovered a genetic mutation found in some breast cancer tumors that could help oncologists predict how well the drug tamoxifen will work for a patient with ER-positive breast cancer. Further studies are needed to explore just how useful the discovery might be.

“Researchers have identified genes that may help predict whether a patient with estrogen receptor (ER)-positive breast cancer is likely to benefit from tamoxifen therapy, according to a study published in the July 15 issue of Cancer Research.

“Hendrika M. Oosterkamp, M.D., of The Netherlands Cancer Institute in Amsterdam, and colleagues conducted a large-scale loss-of-function genetic screen in ZR-75-1 luminal breast cancer cells to identify candidate genes for tamoxifen resistance.

“The researchers found that loss of function in the deubiquitinase USP9X prevented proliferation arrest by tamoxifen, but not by the ER downregulator fulvestrant. RNAi-mediated attenuation of USP9X stabilized ERα on chromatin in the presence of tamoxifen, and this caused a global activation of ERα-responsive genes driven by tamoxifen. A gene signature defined by differential expression after USP9X attenuation in the presence of tamoxifen was used to identify patients with ERα-positive breast cancer experiencing a poor outcome after adjuvant therapy with tamoxifen. Correlation of the gene signature with survival was not observed in patients with breast cancer who did not receive endocrine therapy.

” ‘Overall, our findings identify a gene signature as a candidate biomarker of response to tamoxifen in breast cancer,’ the authors write.”