Hematologic adverse events following palbociclib dose reduction in patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer: pooled analysis from randomized phase 2 and 3 studies

Ettl, Johannes; Im, Seock Ah; Ro, Jungsil; Masuda, Norikazu; Colleoni, Marco; Schnell, Patrick; Bananis, Eustratios; Lu, Dongrui R.; Cristofanilli, Massimo; Rugo, Hope S.; Finn, Richard S.

doi:10.1186/s13058-020-01263-0

Cited by 30 publications

(25 citation statements)

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“…Neutropenia is a known, common, and potentially serious AE associated with palbociclib and all CDK4/6 inhibitors [1, 18, 19]. However, dose reductions, dosing interruptions, or cycle delays of palbociclib have been shown to effectively manage neutropenia without compromising the benefits of palbociclib plus ET combination therapy [20–22]. Findings from a recent analysis of data pooled from the three PALOMA studies showed that reducing palbociclib dose decreased the frequency and severity of neutropenia regardless of patients’ ethnicity, body mass index, or age [20].…”

Section: Discussionmentioning

confidence: 99%

“…However, dose reductions, dosing interruptions, or cycle delays of palbociclib have been shown to effectively manage neutropenia without compromising the benefits of palbociclib plus ET combination therapy [20–22]. Findings from a recent analysis of data pooled from the three PALOMA studies showed that reducing palbociclib dose decreased the frequency and severity of neutropenia regardless of patients’ ethnicity, body mass index, or age [20]. Importantly, a landmark analysis of data from PALOMA‐2 demonstrated that PFS in patients receiving palbociclib plus letrozole was similar between those whose dose was reduced and those who did not have their dose reduced [22].…”

Section: Discussionmentioning

confidence: 99%

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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

et al. 2021

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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“…50 In our study, lower BMI correlated with higher rates of neutropenia, which was also seen in a recent pooled analysis of two trials testing palbociclib. 53 Perhaps, besides interethnic variabilities, differences in BMI could be one of the mechanistic reasons why Asian patients present higher neutropenia rates with these CDK 4/6 inhibitors. A possible explanation for the lower neutropenia rates in overweight/obese patients could refer to the fact that higher blood neutrophil counts might be a potential inflammatory biomarker of overweightness/obesity, as already shown in non-cancer patients.…”

Section: Discussionmentioning

confidence: 99%

Clinical Implications of Body Mass Index in Metastatic Breast Cancer Patients Treated With Abemaciclib and Endocrine Therapy

Franzoi

Eiger

Ameye

et al. 2020

JNCI: Journal of the National Cancer Institute

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Background There are limited data regarding the impact of body mass index (BMI) on outcomes in advanced breast cancer, especially in patients treated with endocrine therapy (ET) + cyclin-dependent kinase 4/6 inhibitors. Methods A pooled analysis of individual patient-level data from MONARCH 2 and 3 trials was performed. Patients were classified according to baseline BMI into underweight (<18.5 kg/m2), normal (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), and obese (≥30 kg/m2) and divided into 2 treatment groups: abemaciclib + ET vs placebo + ET. The primary endpoint was progression-free survival (PFS) according to BMI in each treatment group. Secondary endpoints were response rate, adverse events according to BMI, and loss of weight (≥5% from baseline) during treatment. Results This analysis included 1138 patients (757 received abemaciclib + ET and 381 placebo + ET). There was no difference in PFS between BMI categories in either group, although normal-weight patients presented a numerically higher benefit with abemaciclib + ET (Pinteraction = .07). Normal and/or underweight patients presented higher overall response rate in the abemaciclib + ET group compared with overweight and/or obese patients (49.4% vs 41.6%, odds ratio = 0.73, 95% confidence interval = 0.54 to 0.99) as well as higher neutropenia frequency (51.0% vs 40.4%, P = .004). Weight loss was more frequent in the abemaciclib + ET group (odds ratio = 3.23, 95% confidence interval = 2.09 to 5.01). Conclusions Adding abemaciclib to ET prolongs PFS regardless of BMI, showing that overweight or obese patients also benefit from this regimen. Our results elicit the possibility of a better effect of abemaciclib in normal and/or underweight patients compared with overweight and/or obese patients. More studies analyzing body composition parameters in patients under treatment with cyclin-dependent kinase 4/6 inhibitors may further clarify this hypothesis.

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“…Many pooled‐analyses of PALOMA trials have been performed to focus on dose reduction patterns. In the group of patients that need dose reduction in PALOMA trials, there are more Asian women, the mean weight is lower, and basal neutrophil count is slightly lower than in no‐reduction group 5 . However, dose reduction does not appear to impact on survival outcomes in any post hoc analysis 6,7 …”

Section: Figurementioning

confidence: 99%

Predictive variables of palbociclib dose reduction and its impact on survival outcomes: A retrospective bicentric study

Ogliari¹,

Caspani²,

Rossi³

et al. 2021

Breast J

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Hematologic adverse events following palbociclib dose reduction in patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer: pooled analysis from randomized phase 2 and 3 studies

Cited by 30 publications

References 20 publications

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

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

Clinical Implications of Body Mass Index in Metastatic Breast Cancer Patients Treated With Abemaciclib and Endocrine Therapy

Predictive variables of palbociclib dose reduction and its impact on survival outcomes: A retrospective bicentric study

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