Older Age Associated With Palbociclib Dose Reduction in Patients With Advanced Breast Cancer

A study presented at the Hematology/Oncology Pharmacy Association Annual Conference 2024 utilized data from a real-world setting to identify predictive factors for dose reduction among patients with advanced or metastatic breast cancer receiving palbociclib.

In total, 149 patients treated at a single center in Montreal, Quebec, Canada, were included. Patients had locally advanced unresectable or metastatic HR+/HER2− breast cancer and were treated with palbociclib in combination with letrozole (59.7%) or fulvestrant (40.3%). The primary end point was the identification of baseline characteristics that were predictive for the need for palbociclib dose reduction during treatment. Other end points included treatment patterns, clinical outcomes (including progression-free survival [PFS]), and the frequency and type of interventions carried out by oncology pharmacists for these patients.

Overall, 37.6% of patients required a dose reduction. The number of dose reductions ranged from 1 to 3. The recommended starting dose was 125 mg/day, and the average dose after first reduction was 100 mg/day. The average time to first reduction was 99.5 days.

The most common reason for the initial dose reduction was advanced age (42.8%), followed by comorbidities (28.6%), prevention of toxicities (21.4%), drug interaction (14.3%), Eastern Cooperative Oncology Group performance status ≥2 (14.3%), and hepatic insufficiency (7.1%). When considering all dose reductions during treatment, the most common reason for reductions was side effects (93.4%)—in 84.7% of cases, the side effect responsible for the dose reduction was neutropenia.

Median PFS was 20.4 months (95% CI, 9.6-31.3) in the dose reduction group and 14.1 months (95% CI, 9.1-19.1) in the no reduction group. The average number of pharmacist interventions per patient was 14.4 (range, 3.0-73.0). The most common types of pharmacist intervention were an oncology nurse call (17.5%), community pharmacy calls (13.7%), and an initial meeting with education (12.5%).

Assessment of predictive factors of dose reduction showed that absolute neutrophil count (ANC) <3.5 × 10⁹/L at the start of treatment and age ≥70 years were both significantly associated with reduction. The odds ratio (OR) for dose reduction with an ANC <3.5 × 10⁹/L was 3.120 (95% CI, 1.516-6.422; P=.002). The OR for age ≥70 years was 2.1 (95% CI, 1.063-4.148; P=.033).

In summary, the authors wrote, “These real-world data suggest that patients aged ≥70 years and those whose ANC before initiating treatment is <3.5 × 10⁹/L may benefit from an upfront dose reduction as they are at higher risk for a dose reduction of palbociclib during treatment.”

Reference

Savignan S, Boyer M, Messier C, Monfette ML, Letarte N. Predictive factors of dose reduction among patients treated with palbociclib for advanced or metastatic breast cancer in a real-world setting. Poster. Presented at the Hematology/Oncology Pharmacy Association Annual Conference 2024; April 3-6, 2024; Tampa, Florida.