FDA Approves Palbociclib/Ibrance for HER2-Negative, Advanced Breast Cancer

“Federal health regulators on Tuesday approved a highly anticipated medicine from Pfizer Inc. to treat postmenopausal women with a certain type of advanced breast cancer who have not already taken other drugs.

“The Food and Drug Administration approved Ibrance for women who have tumors that do not contain a protein known as HER-2. Ibrance, known generically as palbociclib, works by blocking molecules linked to .

“Pharmaceutical industry analysts expect Ibrance to grow into a mega-blockbuster, with annual sales as high as $4 billion by 2020.

“The drug is intended to be used in combination with another cancer medication known generically as letrozole.

“The FDA granted the drug accelerated approval—more than two months ahead of its April 13 target date—based on a 165-patient study showing that it slowed the progression of . Patients taking Ibrance and letrozole lived 20.2 months on average before their tumors worsened. That was about twice as long as the benefit for women in a comparison group who only received letrozole. The study is ongoing and it’s not yet clear whether Ibrance’s benefits result in increased survival times for patients.”


FDA Has Not Yet Planned Meeting to Evaluate Palbociclib for Postmenopausal Women with Advanced ER+ HER2- Breast Cancer

The gist: In October, the U.S. Food and Drug Administration (FDA) announced that it had granted Priority Review to new breast cancer drug palbociclib, meaning that it would speed its review process to get the drug to more patients sooner. However, as of January 2015, the FDA has not yet planned a meeting to evaluate the drug. The reason for the delay has not been announced. Palbociclib has shown promise for postmenopausal women with advanced, ER-positive, HER2-negative breast cancer. If it is approved by the FDA, doctors across the U.S. will be able to prescribe palbociclib to these patients.

“The U.S. Food and Drug Administration isn’t planning an advisory committee meeting at this time to evaluate Pfizer Inc.’s experimental breast-cancer treatment, despite the drug having received priority-review status in October, the company said Thursday.

“Pfizer didn’t provide reasons for the delay, but said it continues to talk with the FDA about the application for palbociclib, also known by the brand name Ibrance.

“An FDA spokesperson wasn’t immediately available to respond.

“The drug is one of many experimental therapies that targets certain proteins in the body known as CDKs. Cancer hijacks these proteins to help tumor cells grow. Recent studies suggest that stopping these proteins can help stall cancer.”


Adding Palbociclib to Letrozole Treatment Delays Cancer Worsening in Postmenopausal Women with Advanced ER+ HER2- Breast Cancer

The gist: Adding the drug palbociclib to letrozole treatment might help delay cancer getting worse in postmenopausal women with advanced, ER-positive, HER2-negative breast cancer. That was the conclusion of a recent clinical trial that tested the drug combo in volunteer patients. The trial specifically tested the palbociclib/letrozole combo as a “first-line” treatment, meaning the first drugs given to a patient to treat their advanced cancer.

“In the phase II PALOMA-1/TRIO-18 trial reported in The Lancet Oncology, Finn et al found that the addition of palbociclib to letrozole resulted in significant improvement in progression-free survival as first-line treatment for advanced disease in postmenopausal women with estrogen receptor–positive/HER2-negative breast cancer. Palbociclib is an oral small-molecule inhibitor of cyclin-dependent kinases 4 and 6.

“In the open-label study, patients were enrolled in two sequential cohorts, one including patients on the basis of estrogen receptor–positive/HER2-negaitve status alone (cohort 1) and another that required presence of amplification of cyclin D1 (CCND1), loss of p16 (INK4A or CDKN2A), or both (cohort 2). In both cohorts, patients were randomly assigned between December 2009 and May 2012 to receive continuous letrozole at 2.5 mg daily with or without palbociclib at 125 mg once daily for 3 weeks followed by 1 week off in 28-day cycles…

“The investigators concluded: ‘The addition of palbociclib to letrozole in this phase 2 study significantly improved progression-free survival in women with advanced oestrogen receptor-positive and HER2-negative breast cancer. A phase 3 trial is currently underway.’ “


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.”


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).”


Pfizer Submits NDA For Breast Cancer Drug Palbociclib Combined With Letrozole

Editor’s note: Before a new cancer treatment can be prescribed by doctors in the U.S., it must be approved by the U.S. Food and Drug Administration (FDA). Recently, the drug company Pfizer submitted an application to the FDA in the hopes that its new breast cancer treatment might be approved. The treatment combines two drugs called palbociclib and letrozole. It is specifically meant for treating advanced or metastatic breast cancer in post-menopausal women whose tumors have tested ER+ and HER2-. In addition, the women must not have already taken any other cancer treatments that travel through the bloodstream. The new treatment has performed well in a clinical trial with volunteer patients.

“Pharma giant Pfizer, Inc. ( PFE ) announced Monday that it submitted a New Drug Application or NDA, to the U.S. Food and Drug Administration or FDA, for palbociclib, in combination with letrozole, as first-line systemic treatment advanced or metastatic breast cancer in post-menopausal women.

” ‘Today’s submission marks an important milestone for Pfizer and palbociclib, and a potential advance for women with advanced breast cancer,’ said Garry Nicholson, President, Pfizer Oncology.

” is an investigational oral targeted agent that selectively inhibits cyclin-dependent kinases 4 and 6 to regain cell cycle control and block tumor cell proliferation.

“The NDA seeks approval for the treatment of 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.”


Palbociclib Plus Letrozole Extended PFS in Metastatic Breast Cancer

“The addition of palbociclib to letrozole during first-line treatment significantly extended PFS in post-menopausal patients with ER-positive, HER-2–negative advanced breast cancer, according to final results of a randomized, open-label, phase 2 trial presented at the American Association for Cancer Research annual meeting.

“Palbociclib (PD-0332991, Pfizer), an inhibitor of cyclin-dependent kinases (CDK) 4 and 6, prevents DNA synthesis by blocking cell cycle progression. Results of preclinical studies showed HR-positive breast cancer cells are dependent on CDK-4/6 for growth, and a phase 1 study showed the combination of palbociclib and the antiestrogen drug letrozole appeared to be a safe, effective combination.”

Editor’s note: “PFS” stands for “progression-free survival.” It refers to a period of time in which a cancer patient does not experience worsening of his/her disease. In the clinical trial described here, a combination of two drugs —palbociclib and letrozole—extended PFS for some people with ER-positive, HER-2-negative advanced breast cancer.


Squamous Lung Cancer ‘Master Protocol’ Brings Cancer Research into the 21st Century


Clinical trials help determine whether new cancer treatments are safe and effective, and they provide access to cutting-edge drugs that patients wouldn’t otherwise be able to have. But the clinical trial system is notoriously inefficient, slow, expensive, and laborious. Now, a new and ambitious clinical trial design called the Lung Cancer Master Protocol seeks to overhaul the system, promising to benefit patients and drug companies alike. Continue reading…


Competitors Collaborate on Melanoma Combo Treatment

Two pharmaceutical giants are teaming up on a phase I/II clinical trial to see if their anti-melanoma drugs work better together than on their own. The drugs are GlaxoSmithKline’s Mekinist (trametinib), a U.S. Food and Drug Administration (FDA)-approved MEK inhibitor (a drug that targets MEK proteins), and Pfizer’s palbociclib, an experimental inhibitor of proteins called cyclin dependent kinases. These proteins make cells divide and are abnormally active in many cancers; the FDA has fast-tracked the review of using palbociclib to treat breast cancer. In addition, GlaxoSmithKline is already testing the combination of Mekinist with dabrafenib, the company’s experimental BRAF inhibitor.