Expanded-Access Study of Palbociclib in Combination With Letrozole for Treatment of Postmenopausal Women With Hormone Receptor–Positive, HER2-Negative Advanced Breast Cancer

Abstract Purpose Palbociclib is a cyclin-dependent kinase (CDK) 4 and 6 inhibitor that was conditionally approved in the United States (February 2015) and Canada (March 2016) with letrozole as initial endocrine-based therapy for postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. A palbociclib expanded-access program (EAP) was initiated as an interim measure to provide drug access before commercial availability of drug. Patients and Methods Eligible women were 18 years or older and postmenopausal with diagnosed metastatic HR-positive, HER2-negative breast cancer and were suitable candidates for letrozole therapy. Treatment continued until disease progression, unacceptable toxicity, withdrawal of consent, or commercial availability of palbociclib. We report combined safety data in both cohorts, and patient-reported outcomes in the Canadian cohort. Results From September 2014 to May 2016, a total of 334 patients were enrolled onto the EAP. With rapid regulatory approval and transfer to commercial supply, median duration of palbociclib treatment while on study was 77 days (range, 2-245 days). At least one dose reduction occurred in 24.3% of patients, and 3.6% of patients permanently discontinued palbociclib because of treatment-emergent adverse events. The most common adverse events (> 20%) of any grade included neutropenia (66.5%), fatigue (38%), infection (25.4%), and nausea (22.5%). Grade 3/4 adverse events included neutropenia (54.5%), leukopenia (8.1%), fatigue (4.2%), anemia (3.9%), thrombocytopenia (3.6%), infection (3.3%), and febrile neutropenia (2.1%). Conclusion In a real-world EAP setting, palbociclib in combination with letrozole was well tolerated, and the safety profile was consistent with other reported clinical trial literature of HR-positive, HER2-negative advanced breast cancer.