Pfizer Receives Expanded FDA Approval For Ibrance (palbociclib) In HR , HER2- Metastatic Breast Cancer

In continuation of my updates on palbociclib

Pfizer Inc. (NYSE:PFE) announced that the U.S. Food and Drug Administration (FDA) has approved a new indication expanding the use of Ibrance (palbociclib) 125mg capsules, Pfizer’s metastatic breast cancer therapy. Now Ibrance also is approved for the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer in combination with fulvestrant in women with disease progression following endocrine therapy.1 Pfizer’s supplemental New Drug Application (sNDA) for Ibrance was reviewed and approved under the FDA’s Breakthrough Therapy designation and Priority Review programs based on results from the Phase 3 PALOMA-3 trial in pre-, peri- and post-menopausal women with HR+, HER2- metastatic breast cancer whose disease progressed on or after prior endocrine therapy in the adjuvant or metastatic setting.

Ibrance first was approved in February 2015 and also is indicated for the treatment of HR+, HER2- advanced or metastatic breast cancer in combination with letrozole as initial endocrine-based therapy in postmenopausal women.1 The indication in combination with letrozole is approved under accelerated approval based on progression-free survival (PFS). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.1 The confirmatory Phase 3 trial, PALOMA-2, is fully enrolled.

Ibrance is the first and only cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor approved by the FDA.

Pfizer Receives Expanded FDA Approval For Ibrance (palbociclib) In HR , HER2- Metastatic Breast Cancer

New oral breast cancer drug has potential to combat other types of cancer

In continuation of my update on Palbociclib

Palbociclib, a new oral drug whose efficacy in combating breast cancer has been demonstrated alone and in combination with endocrine therapy, also has potential to combat other types of cancer, according to a literature review and additional original research conducted by experts at the Abramson Cancer Center (ACC) in the University of Pennsylvania published this month in JAMA Oncology.

Palbociclib targets the rapid division of tumor cells by inhibiting the activity of the enzymes CDK4 and CDK6, which propel cell division and increase in number in most cancers. It is the first CDK4/6 inhibitor to be approved for the treatment of breast cancer.

"All living cells undergo cell division and palbociclib's unique capacity to halt the cell division process (also known as the 'cell cycle') therefore has potentially broad applicability," said the study's lead author Amy S. Clark, MD, MSCE, an assistant professor of Hematology/Oncology at Penn's Perelman School of Medicine and ACC. "Pairing palbociclib with other anti-cancer therapies such as endocrine therapy, chemotherapy, and targeted therapy can create a powerful combinatorial effect with real promise for addressing a variety of cancers." For example, amplification of CDK4 is reported in a high percentage of melanomas and esophageal cancers.

Targeted therapy uses medication and other interventions to more accurately identify and attack cancer cells, usually while doing no or little damage to normal cells.

"This drug has minor effects on normal cells other than neutrophils (white blood cells)," said the study's senior author, Peter J. O'Dwyer, MD, a professor of Hematology/Oncology at Penn and director of the Developmental Therapeutics Program at the ACC. "In tumors, it can cause shrinkage, or more commonly, arrest of growth. As we discover new functions for the CDK4/6 target of this medicine, we are likely to use it in combinations to make other anti-cancer agents work better."

New oral breast cancer drug has potential to combat other types of cancer

New Breast Cancer Drug May Be Effective Against Other Types of Cancer, Abramson Cancer Center Experts Find

In continuation of my update on Palbociclib,

Palbociclib, a new oral drug whose efficacy in combating breast cancer has been demonstrated alone and in combination with endocrine therapy, also has potential to combat other types of cancer, according to a literature review and additional original research conducted by experts at the Abramson Cancer Center (ACC) in the University of Pennsylvania published this month in JAMA Oncology.

Palbociclib targets the rapid division of tumor cells by inhibiting the activity of the enzymes CDK4 and CDK6, which propel cell division and increase in number in most cancers. It is the first CDK4/6 inhibitor to be approved for the treatment of breast cancer.

“All living cells undergo cell division and palbociclib’s unique capacity to halt the cell division process (also known as the ‘cell cycle’) therefore has potentially broad applicability,” said the study’s lead author Amy S. Clark, MD, MSCE, an assistant professor of Hematology/Oncology at Penn’s Perelman School of Medicine and ACC. “Pairing palbociclib with other anti-cancer therapies such as endocrine therapy, chemotherapy, and targeted therapy can create a powerful combinatorial effect with real promise for addressing a variety of cancers.” For example, amplification of CDK4 is reported in a high percentage of melanomas and esophageal cancers.

Targeted therapy uses medication and other interventions to more accurately identify and attack cancer cells, usually while doing no or little damage to normal cells. 

“This drug has minor effects on normal cells other than neutrophils (white blood cells),” said the study’s senior author, Peter J. O’Dwyer, MD, a professor of Hematology/Oncology at Penn and director of the Developmental Therapeutics Program at the ACC. “In tumors, it can cause shrinkage, or more commonly, arrest of growth. As we discover new functions for the CDK4/6 target of this medicine, we are likely to use it in combinations to make other anti-cancer agents work better.”

In addition to inhibiting the cell cycle, palbociclib has been shown, for example, to alter several recently described non–cell cycle functions of CDK4/6, a finding expected to expand its therapeutic role, O’Dwyer added.

Assessing 130 relevant publications in the literature, as well as interpreting their own continuing studies, the all-Penn team found that in addition to its safety and effectiveness in fighting certain types of breast cancer, early trials of palbociclib have shown promise of effectiveness in cases of lymphoma, sarcoma, and teratoma, tumors that while rare, often afflict younger patients.

A phase 2 trial showed that, among 17 patients with previously treated mantle-cell lymphoma, palbociclib resulted in one complete response and two partial responses. Although, median progression-free survival was four months, five patients had progression-free survival greater than one year. Another phase 2 trial with 29 sarcoma patients treated with palbociclib showed a progression-free survival of 66 percent at 12 weeks.

Also, combining palbociclib with other anti-cancer agents is feasible, and early results in myeloma and some solid tumors have led to more definitive studies.

New Breast Cancer Drug May Be Effective Against Other Types of Cancer, Abramson Cancer Center Experts Find

PALOMA3 supports palbociclib use in advanced breast cancer

In continuation of my update on palbociclib... 

Advanced breast cancer patients who have failed prior endocrine treatment may receive a progression-free survival (PFS) benefit if palbociclib is added to fulvestrant, a phase III trial indicates.

The advantage accorded by the small-molecule inhibitor of CDK4 and CDK6 was irrespective of the menopausal status of the women, the team reports in The New England Journal of Medicine.

The research was concurrently presented at the annual meeting of the American Society of Clinical Oncology, held in Chicago, Illinois, USA.

The double-blind PALOMA3 trial comprised women with advanced breast cancer positive for oestrogen and/or progesterone hormone receptors but negative for epidermal growth factor receptor 2 who had progressed or relapsed during endocrine therapy.

PALOMA3 supports palbociclib use in advanced breast cancer

Palbociclib extends progression-free survival in advanced breast cancer patients

In continuation of my update on Palbociclib

Palbociclib, an investigational oral medication that works by blocking molecules responsible for cancer cell growth, is well tolerated and extends progression-free survival (PFS) in newly diagnosed, advanced breast cancer patients, including those whose disease has stopped responding to traditional endocrine treatments. Results of the phase II study, led by researchers in the Abramson Cancer Center and the Perelman School of Medicine at the University of Pennsylvania , were published this month in Clinical Cancer Research. Earlier phase I results by researchers at Penn Medicine contributed to the development of palbociclib, which was recently approved by the U.S. Food and Drug Administration (FDA) for metastatic breast cancer patients just beginning to undergo endocrine therapy.

"The FDA approval has expanded treatments options for many metastatic breast cancer patients, but these new results are showing how effective the drug can also be for breast cancer patients who have already tried endocrine therapies and may be running out of options," said lead investigator Angela DeMichele, MD, MSCE , associate professor in the division of Hematology/Oncology and Epidemiology and co-leader of the Breast Cancer Research Program at the Abramson Cancer Center. "Combined with the promising results from other trials looking at the effectiveness of this drug, our results indicate that palbociclib can extend the duration of disease control and produce tumor shrinkage in patients with estrogen-receptor positive (ER+) breast cancer, without the debilitating side effects of chemotherapy."

The newly-published phase II trial primarily sought to evaluate disease response and control, while monitoring for the presence of side effects such as neutropenia, an abnormally low white blood cell count. Patients enrolled in the trial had previously undergone several prior chemotherapy and hormonal regimens for metastatic disease. Palboclib was administered once daily for 21 days each month.

Overall, researchers noted a median PFS, the time before a tumor worsens or the patient dies, of 3.7 months for patients taking the drug. However, patients with hormone receptor-positive (HR+) breast cancer -where the breast cancer cells depend on the hormones estrogen and progesterone to grow - had significantly longer PFS (5.1 months) compared to that of the HR-negative group (84 percent and 11 percent of the enrolled population, respectively). And those who had previously progressed through at least two rounds of hormonal therapy saw significantly greater benefits, suggesting substantial activity in the setting of acquired endocrine resistance.

Palbociclib extends progression-free survival in advanced breast cancer patients