Long-Term Pooled Safety Analysis of Palbociclib in Combination with Endocrine Therapy for Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Updated Analysis with up to 5 Years of Follow-Up

Abstract

Background Previous studies demonstrated the tolerability of palbociclib plus endocrine therapy (ET). This analysis evaluated safety based on more recent cutoff dates and a longer palbociclib treatment exposure. Patients and Methods Data were pooled from three randomized studies of patients with hormone receptor‐positive/human epidermal growth factor receptor 2‐negative (HR+/HER2−) advanced breast cancer (ABC), including postmenopausal women who had not received prior systemic treatment for advanced disease (PALOMA‐1/‐2) and pre‐ and postmenopausal women who had progressed on prior ET (PALOMA‐3). Results Updated cutoff dates were December 21, 2017 (PALOMA‐1), May 31, 2017 (PALOMA‐2), and April 13, 2018 (PALOMA‐3). Total person‐years of treatment exposure were 1,421.6 with palbociclib plus ET (n = 872) and 528.4 with ET (n = 471). Any‐grade neutropenia and infections were more frequent with palbociclib plus ET (82.1% and 59.2%, respectively) than with ET (5.1% and 39.5%). The hazard ratios were 1.6 (p = .0995) for grade 3/4 infections, 1.8 (p = .4358) for grade 3/4 viral infections, 1.4 (p = .0001) for infections, and 30.8 (p < .0001) for neutropenia. Febrile neutropenia was reported in 1.4% of patients receiving palbociclib plus ET. Cumulative incidence of all‐grade hematologic adverse events in both arms peaked during the first year of treatment and plateaued over the 5 subsequent years. Interstitial lung disease was reported in 13 patients receiving palbociclib plus ET and 3 receiving ET. Conclusion This 5‐year, long‐term analysis demonstrated that palbociclib plus ET has a consistent and stable safety profile and is a safe treatment for patients with HR+/HER2− ABC. Implications for Practice Several treatments for patients with breast cancer are associated with long‐term or latent adverse events. This long‐term, 5‐year analysis demonstrated that palbociclib plus endocrine therapy has a consistent and stable safety profile without cumulative or delayed toxicities. These results further support palbociclib plus endocrine therapy as a safe and manageable treatment in clinical practice for patients with hormone receptor‐positive/human epidermal growth factor receptor 2‐negative advanced breast cancer.

Efficacy and safety of palbociclib in patients with estrogen receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer with preexisting conditions: A post hoc analysis of PALOMA-2

“…Given that there were no new safety signals observed in patients with preexisting conditions, it is perhaps unsurprising that palbociclib dose modifications were similar across preexisting condition subgroups. In the overall PALOMA-2 population, 39.4 % of patients receiving palbociclib plus letrozole experienced a dose reduction [ 13 ]. This is similar to the rates of palbociclib dose reduction in each of the preexisting condition subgroups reported here.…”

Palbociclib as an early-line treatment for Japanese patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer: a review of clinical trial and real-world data

“…Similar to PALOMA-2 and PALOMA-3, commonly reported AEs in real-world studies included neutropenia, other hematologic AEs, and fatigue [48,49,52]. Of note, interstitial lung disease was also observed with CDK4/6 inhibitors in the real-world setting as well as PALOMA studies [27,53]. Additionally, real-world data were utilized to expand the approved indications of palbociclib to include male patients with ABC in 2019 [54].…”

“…In PALOMA-3, among patients in the palbociclib plus fulvestrant group, 53.3% experienced grade 3 and 8.7% experienced grade 4 neutropenia; febrile neutropenia was reported in 0.6% of patients [ 17 ]. A pooled analysis of data from the PALOMA-1, -2, and -3 trials showed that interstitial lung disease was reported in 1.5% of patients receiving palbociclib plus endocrine therapy and that the incidence of interstitial lung disease was similar across geographic locations [ 27 ]. Additionally, quality of life was maintained in patients treated with palbociclib plus endocrine therapy [ 28 , 29 ].…”

Outcome in patients of hormone receptor (HR) positive (Her 2) negative metastatic breast cancer treated with palbociclib – A real-world experience

“…[5] The PFS and toxicity analysis results are consistent with other reports of routine clinical practice, that is, real-world evidence from India and other countries and the global clinical trials. [6][7][8][9][10][11][12][13][14][15][16][17] The observed OS is lower than reported in real-world studies and clinical trials. Our analysis suggests that patients who were less heavily pre-treated had better outcomes.…”