Chicago—The cyclin-dependent kinase-4 and -6 inhibitor palbociclib improves progression-free survival in patients with estrogen receptor-positive, metastatic breast cancer (and potentially in other forms of cancer, as well). However, treatment with palbociclib is also associated with severe neutropenia (grade 3 or 4), which can affect treatment adherence and overall outcomes.
To better understand the overall risk of palbociclib-associated neutropenia, Yan Mao, MD, and colleagues at The Affiliated Hospital of Qingdao University Medical College in China, and the University of Southern California Norris Comprehensive Cancer Center in Los Angeles, conducted a systematic literature search of abstracts presented at the American Society of Clinical Oncology (ASCO) Annual Meetings from 2009 to 2016, and clinical trials published in Web of Science, Medline, and other databases through November 2016.
A total of eight studies published between 2012 and 2016, involving 1515 patients with cancer, were eligible for inclusion. Results were presented in a publication-only abstract published in conjunction with the 2017 ASCO Annual Meeting.
For their meta-analysis, the authors evaluated data from prospective clinical trials involving patients with cancer treated with daily palbociclib 125 mg for 3 to 4 weeks that also had available data on neutropenia. They calculated incidence and relative risk (RR) of neutropenia in this cohort by using “a random-effects or fixed-effects model, depending on the heterogeneity of the included studies.”
In patients treated with palbociclib, the incidence of all-grade neutropenia was 77.4% (95% confidence interval [CI], 70.9-82.8), and the incidence of high-grade neutropenia was 60.9% (95% CI, 57.8-63.8). The authors reported a significant difference in neutropenia incidence between patients with metastatic breast cancer and patients whose disease had not metastasized (all-grade neutropenia: RR, 1.26; 95% CI, 1.01-1.56; p=0.041; high-grade neutropenia: RR, 1.57; 95% CI, 1.23-2.00; p=0.000).
Treatment with palbociclib was also associated with “a significantly increased risk of all-grade neutropenia in patients with cancer with an RR of 15.03 (95% CI, 10.17-22.21; p<0.001) compared with controls.”
Because patients with breast cancer (especially patients with metastatic disease) treated with palbociclib are at significant risk for developing neutropenia, the authors recommended that treating clinicians monitor these patients to adjust dose and modify treatment intervals to avoid infections.
Source: Mao Y, Lu J, Wang H, Nie G. Incidence and risk of neutropenia with palbociclib in patients with cancer: A systematic review and meta-analysis. J Clin Oncol 35, 2017 (suppl; abstr e12530).