Long-Term Pooled Safety Data for Palbociclib Combined With Endocrine Therapy in HR-Positive, HER2-Negative Breast Cancer


Key Points

  • Palbociclib plus endocrine therapy was associated with more neutropenia and infections vs endocrine therapy alone.
  • The highest incidence of adverse events was during the first 6 months of treatment.

In an analysis of pooled safety data from the PALOMA trials of palbociclib plus endocrine therapy in hormone receptor (HR)-positive, HER2-negative advanced breast cancer reported in the Journal of the National Cancer Institute, Diéras et al found no evidence of specific cumulative or delayed palbociclib toxicity over long-term follow-up.

Study Details

The phase II PALOMA-1 trial and phase III PALOMA-2 trial included postmenopausal women who had received no prior treatment for advanced disease; the phase III PALOMA-3 trial included women of any menopausal status with advanced disease progressing on prior endocrine therapy. Front-line patients were randomized to receive letrozole with or without palbociclib (PALOMA-1) or letrozole plus either palbociclib or placebo (PALOMA-2). In PALOMA-3, patients received fulvestrant plus palbociclib or placebo. Overall, 872 evaluable patients received palbociclib plus endocrine therapy and 471 received endocrine therapy alone. Cumulative adverse event rates were reported for up to 50 months of treatment.

Adverse Event Profile

The most common adverse events of any grade with palbociclib plus endocrine therapy were neutropenia, which occurred in 81% of patients (grade ≥ 3 in 65%) and infections, which occurred in 55% (grade ≥ 3 in 5%); corresponding incidence rates in the endocrine monotherapy group were 5.3% (grade ≥ 3 in 1%) and 37% (grade ≥ 3 in 2.5%). The incidence of any grade adverse events reported for ≥ 15.0% of palbociclib patients exhibited a similar trend over time, peaking during the first 6 months of treatment and generally decreasing thereafter. With the exception of neutropenia, leukopenia, and infections, the incidence of individual adverse events remained at < 15.0% during each 6-month interval after the first 6 months. The most common hematologic adverse events (≥ 15.0%) were more likely to be reported during the initial months of treatment, after which there was no substantial increase in cumulative event rate. Adverse events led to discontinuation of treatment in 8.3% of patients receiving palbociclib plus endocrine therapy over 3 years.

The investigators concluded, “Based on these long-term safety analyses, there is no evidence of specific cumulative or delayed toxicities with palbociclib plus endocrine therapy, supporting the ongoing investigation of palbociclib plus endocrine therapy in early breast cancer.”

The study was supported by Pfizer Inc.

Véronique Diéras, MD, of the Institut Curie, Paris, is the corresponding author for the Journal of the National Cancer Institute article.

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