FDA Expands Palbociclib Approval for Breast Cancer

“The Food and Drug Administration (FDA) has granted an expanded indication for the cyclin-dependent kinase 4/6 inhibitor palbociclib (Ibrance). The drug is now approved for use in combination with fulvestrant in women with hormone receptor (HR)-positive, HER2-negative advanced or metastatic breast cancer whose disease progressed following endocrine therapy.

“Palbociclib was initially approved in February 2015 for the treatment of estrogen receptor–positive, HER2-negative metastatic breast cancer, in women who had not yet received endocrine therapy. The new approval was granted under the FDA’s breakthrough therapy designation.

“The additional indication for palbociclib is based on results from the PALOMA-3 trial, which was stopped early in April 2015 after an interim analysis showed benefit in combination with fulvestrant when compared to fulvestrant and placebo.”


ESMO Asia 2015 Press Release: Asian Women with Endocrine-Resistant Breast Cancer Benefit from Combination Therapy

“Data collected in Japanese and Korean patients included in the global PALOMA3 trial provides evidence that combining palbociclib with fulvestrant is an effective strategy to overcome endocrine resistance in women with hormone receptor positive (HR+), HER2 negative (HER2-) advanced breast cancer. The analysis of efficacy and safety of the combined therapy in an Asian population will be presented (1) at the first ESMO Asia 2015 Congress in Singapore, and results are in line with those reported in all patients (both Asian and non-Asian) earlier this year.

“Endocrine resistance is a major clinical issue that makes advanced breast cancer more difficult to treat. Hormone therapy is generally well tolerated and an easy-to-administer option for breast cancer, with demonstrated benefits in patients whose tumours express hormone receptors (HR), particularly the HR+/HER2- subgroup. The ideal option for patients is to be on one endocrine therapy after another, as long as the disease responds or remains unchanged. ‘However, unavoidably, resistance develops in almost all advanced patients a median ten months after the first-line hormonal agent is administered, and a much shorter median time after the second- or third-line hormonal agents, eventually driving patients to switch to the more toxic chemotherapy,’ one of the study authors, Dr. Jungsil Ro, Center for Breast Cancer at the National Cancer Center, Goyang, Korea, said.”


Palbociclib's Role in Endocrine-Resistant Breast Cancer

“Palbociclib (Ibrance, Pfizer), the first CDK4/6 inhibitor to be approved for the treatment of breast cancer, has been welcomed by experts for its role in improving outcomes in patients with endocrine-resistant breast cancer.

“The drug should a significant improvement in progression-free survival (PFS) when it was added to fulvestrant (Faslodex, AstraZeneca) in the phase 3 PALOMA 3 trial, as reported recently by Medscape Medical News. The addition of palbociclib to fulvestrant increased median PFS to 9.2 months in patients with estrogen receptor (ER)–positive/HER2-negative endocrine-resistant breast cancer compared with 3.8 months in the placebo-fulvestrant group (P < .001).

“The overall survival data are still immature.

“The full results have now been published in print in the July 16 issue of the New England Journal of Medicine.


Video: Dr. Kari Wisinski on Palbociclib for Metastatic Breast Cancer

“Kari Wisinski, MD, medical oncologist with University Of Wisconsin Health and the University of Wisconsin Carbone Cancer Center, discusses the use of palbociclib for patients with ER-positive and HER2-negative breast cancer.

“Currently there is not a specific patient population that has been identified as ideal for palbociclib, says Wisinski.

“The PALOMA-3 trial demonstrated that palbociclib plus fulvestrant compared with fulvestrant plus placebo improved progression-free survival (PFS) in women with ER-positive and HER2-negative metastatic breast cancer following disease progression. Based on these results, the drug gained accelerated approval in February 2015.

“The PFS data is impressive, says Wisinski, and the swift approval of the drug has benefited patients who need to delay chemotherapy while maintaining PFS.”


Ibrance Trial Stopped Early Because of Strong Evidence of Drug's Efficacy in Metastatic ER+ HER2- Breast Cancer

“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.”