Bo Lively, Mercer University College of Pharmacy
Breast cancer is considered to be one of the most common types of cancer that infects American women. It is estimated that one in eight women in the United States will develop invasive breast cancer during their lifetime.1 Hormone receptor-positive tumors contain both estrogen and progesterone receptors. These cancer cells are sensitive to endogenous female hormones and provide a means to target therapy.2 Current guidelines set forth by the American Society of Clinical Oncology recommended the use of endocrine therapy for women with hormone receptor-positive breast cancer.3 Palbociclib has been recently approved and is indicated in the treatment of hormone receptor-positive breast cancer.4
|Title: Palbociclib in Hormone-Receptor–Positive Advanced Breast Cancer5|
|Design||Double-blind, phase three study; N = 521|
|Objective||To assess the efficacy of palbociclib and fulvestrant in advanced breast cancer|
|Study Groups||Participants were randomized into two groups.
Palbociclib and fulvestrant (n = 345)
Placebo and fulvestrant (n = 172)
|Methods||Participants were randomly assigned to receive palbociclib (125 mg per day orally for 3 weeks, followed by 1 week off) and fulvestrant (500 mg intramuscularly every 14 days for the first three injections and then every 28 days) or matching placebo and fulvestrant.
Treatment continued until objective demonstration of disease progression, unacceptable toxic effects, or withdrawal.
One cycle was defined as three weeks on, followed by one week off (palbociclib or placebo). All patients had to provide tumor samples from a biopsy of a recurrent breast cancer.
Imaging was performed at screening within four weeks before randomization, and then repeated every eight weeks until disease progression.
|Duration||October 7, 2013-August 26, 2014|
|Primary Outcome Measure||Investigator-assessed progression-free survival|
|Baseline Characteristics||The median age was 57 years, 59.7% of the patients had visceral disease, 79.3% were postmenopausal, and 78.7% had cancers that were sensitive to prior endocrine therapy. All patients had human epidermal growth factor receptor 2 (HER2) negative disease, 67.0% had both estrogen-receptor–positive and progesterone-receptor–positive disease, and 26.7% had estrogen-receptor–positive but progesterone-receptor–negative disease.|
|Results||The median progression-free survival was 9.2 months (95% confidence interval [CI], 7.5 to not estimable) with palbociclib–fulvestrant and 3.8 months (95% CI, 3.5 to 5.5) with placebo–fulvestrant (hazard ratio for disease progression or death, 0.42; 95% CI, 0.32 to 0.56; P<0.001).|
|Adverse Events||Common Adverse Events:
Palbociclib-fulvestrant group: neutropenia (78.8 %), leukopenia (45.5%), fatigue (38%), and nausea (29%)
Placebo-fulvestrant group: fatigue (26.7%), nausea (26.2%), and headache (17.4%)
|Serious Adverse Events:
Palbociclib-fulvestrant group: Pyrexia (0.9%), Pulmonary embolism (0.9%)
Placebo-fulvestrant group: Pyrexia (0.6%)
|Percentage that Discontinued due to Adverse Events: None reported|
|Study Author Conclusions||This study showed that adding palbociclib to fulvestrant resulted in substantially longer progression-free survival than fulvestrant alone in patients with advanced hormone receptor-positive breast cancer.|
This study showed that treating hormone receptor-positive breast cancer with palbociclib affords the patient an increased time of progression-free survival. Palbociclib has a unique mechanism and this study proves that palbociclib’s targets represent a new approach in breast cancer treatment. The development of novel drugs such as palbociclib helps continue our pharmacological fight against cancer.
- American Cancer Society.Cancer Facts & Figures 2015. Atlanta, Ga: American Cancer Society; 2015.
- Barnett CM, Michaud L, Esteva FJ. Chapter 105. Breast Cancer. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9e. New York, NY: McGraw-Hill; 2014.
- Burstein HJ, Prestrud AA, Seidenfeld J, et al. American Society of Clinical Oncology clinical practice guideline: update on adjuvant endocrine therapy for women with hormone receptor-positive breast cancer. J Clin Oncol. 2010;28(23):3784-96.
- Product Information: IBRANCE(R) oral capsules, palbociclib oral capsules. Pfizer Inc. (per FDA), New York, NY, 2015.
- Turner NC, Ro J, André F, et al. Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2015;