An analysis of the Dutch Institute for Clinical Auditing (DICA) Medicines project database was conducted to provide insight into real-world use of palbociclib dose reductions and the effect of these dose alterations on overall survival (OS) and time-to-next treatment (TTNT) in older, advanced BC patients. DICA was established by the Dutch government in 2018 to generate real-world data (RWD) from existing data sources, such as administrative and financial sources, to improve the effectiveness of medications in daily clinical practice. TTNT was used as a surrogate for progression-free survival since subsequent doses are administered for disease progression. The initial dose of palbociclib used in the trial was 125 mg once daily.

All HR+ and HER2-negative advanced BC patients from eight general hospitals that participated in the DICA medicine program and who were treated with palbociclib between January 1, 2017, and December 31, 2020, were included in the analysis. Contraindications to the use of palbociclib included hypersensitivity to the drug or the use of St. John's wort. Palbociclib was combined with either aromatase inhibitors or fulvestrant if patients failed endocrine therapy. Patients were screened for the presence of grade 3 and 4 neutropenia, the use of CYP3A4 inhibitors or inducers, relative contraindications, and comorbidities.

The 598 BC patients treated with palbociclib were divided into two groups based on dose reductions: those receiving a dose reduction from 125 mg to 100 mg or to 75 mg (>20% reduction). Separate analyses were conducted for those with an initial dose <125 mg. A subgroup analysis was performed on patients aged 70 years or older as well as those who discontinued therapy early.

The median follow-up time for OS was 12.9 months, and the median age of the study population was 64 years. Almost three-quarters (71%) concomitantly received fulvestrant, whereas 29% received an aromatase inhibitor. There was no difference in median OS between patients receiving combined palbociclib and fulvestrant or an aromatase inhibitor.

Almost 95% of patients (94.5%) started palbociclib at the recommended dose of 125 mg; of those who were administered a reduced initial dose, 64% were older than age 70 years.

Dose reductions were performed in 33% (n = 195) of patients, and almost 60% of these dose alterations occurred within the first 3 months of therapy with a median of 69 days. Patients who received a dose reduction were older (age 67 years) compared with those who did not require a dose reduction (age 63 years; P = .004). Comorbidity scores did not differ between groups. Patients who received a dose reduction had a significantly higher median TTNT (16.9 months vs. 11.4 months; P <.001) and OS (29.7 months vs. 21.9 months; P = .003). Almost one-quarter (23%) of patients who initially started palbociclib treatment discontinued therapy within four courses without a dose reduction.

The authors cautioned that treatment was evaluated 3 to 6 months after starting Palbociclib, and this may have introduced bias for those patients for whom therapy was not reduced but was discontinued and subsequently restarted. Patients who experienced toxicity had a dose reduction, not drug discontinuation, and this may have affected disease progression.

This study provides pharmacists with RWD that patients with advanced BC who have undergone a dose reduction of palbociclib did not fare worse than patients without a dose reduction. This study also provided reassurance that among older BC patients with advanced disease, dose reductions did not affect OS.

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