The Case of the CTCAE Assessment for CDK4/6 Adverse Events
Mrs. Jones is a 66-year-old postmenopausal woman who developed left breast pain and a palpable mass. A mammogram and ultrasound showed a 4.6 cm mass with an enlarged axillary node. A core biopsy revealed invasive ductal carcinoma that is estrogen receptor positive, progesterone receptor positive, and HER2 negative. Positron-emission tomography and computed tomography scans revealed metastatic disease.
The oncology provider prescribes Mrs. Jones palbociclib plus letrozole which, per National Comprehensive Cancer Network guidelines (https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf), is a recommended option for postmenopausal, hormone-receptor positive, HER2-negative, metastatic disease. The palbociclib dose is 125 mg orally daily for 21 days followed by a seven-day rest period (28-day cycle). The letrozole is 2.5 mg orally daily. Which blood work is necessary to obtain prior to initiation of palbociclib?
What Would You Do?
The advent of CDK 4/6 inhibitors has changed the treatment landscape for hormone receptor-positive, HER2-negative advanced or metastatic breast cancer. Currently, three CDK 4/6 inhibitors are U.S. Food and Drug Administration approved in the United States for breast cancer treatment: palbociclib (http://labeling.pfizer.com/ShowLabeling.aspx?id=2191), ribociclib (https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/kisqali.pdf), and abemaciclib (http://pi.lilly.com/us/verzenio-uspi.pdf). Hematologic adverse events are common with CDK 4/6 inhibitors, specifically palbociclib and ribociclib. Although hematologic toxicities (https://doi.org/10.1634/theoncologist.2017-0142) can occur with abemaciclib, gastrointestinal toxicities and fatigue are more common.
Because of the neutropenia risk with palbociclib, a complete blood count should be obtained prior to the initiation of therapy and at the beginning of each cycle, on day 15 of the first two cycles, and as clinically indicated.
On day 17 of cycle 2, Mrs. Jones calls to report increased fatigue and that she “just doesn’t feel well.” Her bloodwork results show an absolute neutrophil count (ANC) of 1,120/mm3, which the Common Terminology Criteria for Adverse Events (CTCAE) classifies as a grade 2 neutropenia (see Table 1). According to the palbociclib (http://labeling.pfizer.com/ShowLabeling.aspx?id=2191) prescribing information, with grade 1 or 2 neutropenia, no dose adjustment is required.
In cycle 4 of therapy, Mrs. Jones ends up hospitalized with a neutropenic fever of 38.8°C and an ANC of 720/mm3, which requires a dose modification to withhold the palbociclib (http://labeling.pfizer.com/ShowLabeling.aspx?id=2191) until the neutropenia recovers to grade 2 or lower and to resume with the next lower dose. The recommended dose modifications for adverse reactions with palbociclib are:
- Starting dose is 125 mg per day.
- First dose reduction is 100 mg per day.
- Second dose reduction is 75 mg per day.
- If further dose reduction is needed beyond 75 mg per day, palbociclib should be discontinued.
Palbociclib and other CDK 4/6 inhibitors have very clear guidelines and recommendations regarding dose modifications related to toxicities. To provide safe care to patients who are prescribed these agents, nurses must be familiar with the recommendations on monitoring for toxicities, how to grade the toxicities if they occur, and where to locate and how to decipher the dose modifications that are recommended.