Long-term Pooled Safety Analysis of Palbociclib in Combination With Endocrine Therapy for HR+/HER2- Advanced Breast Cancer

Dièras, Véronique; Rugo, Hope S.; Schnell, Patrick; Gelmon, Karen A.; Cristofanilli, Massimo; Loi, Sherene; Colleoni, Marco; Lu, Dongrui R.; Mori, Alessia; Gauthier, Eric; Bartlett, Cynthia Huang; Slamon, Dennis J.; Turner, Nicholas C.; Finn, Richard S.

doi:10.1093/jnci/djy109

Cited by 73 publications

(75 citation statements)

References 21 publications

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“…6 A pooled safety analysis conducted across all PALOMA studies demonstrated that grade 3/4 AST and ALT elevations occurred in 3.3% and 2.3% of palbociclibtreated patients, respectively, again highlighting a reported but rare occurrence. 8 The patient described in the present case report started on combination fulvestrant and palbociclib after her disease showed progression on letrozole. She developed an increase in transaminases after completing 3 cycles of palbociclib.…”

Section: Discussionmentioning

confidence: 75%

Elevated liver function tests in a patient on palbociclib and fulvestrant

Roberts¹

2018

JCSO

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Section: Discussionmentioning

confidence: 75%

Elevated liver function tests in a patient on palbociclib and fulvestrant

Roberts¹

2018

JCSO

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“…In a pooled, long-term safety analysis of PALOMA-1, PALOMA-2, and PALOMA-3, 36.9% of patients receiving palbociclib for treatment of HR+/HER2− ABC required dose reduction. Most dose reductions occurred during the first 6 months of treatment and were less frequent during subsequent 28-day treatment cycles (C) than during the first 6 months [9]. Neutropenia and leukopenia were the most common adverse events (AEs) that led to dose reductions in patients treated with palbociclib [9].…”

Section: Introductionmentioning

confidence: 99%

“…Most dose reductions occurred during the first 6 months of treatment and were less frequent during subsequent 28-day treatment cycles (C) than during the first 6 months [9]. Neutropenia and leukopenia were the most common adverse events (AEs) that led to dose reductions in patients treated with palbociclib [9]. The incidence of hematologic and nonhematologic AEs was highest within the first 2 months of palbociclib treatment, which coincided with the period with the most dose modifications (C1-C3) [9].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

Breast Cancer Res

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Background: Palbociclib improves outcomes for women with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer (HR+/HER2− ABC). Dose reductions are recommended for the management of hematologic toxicities. A previous pooled analysis from the PALOMA clinical trials showed that 36.9% of patients required dose reduction, predominantly during the first 6 months of treatment and with decreasing frequency during subsequent 28-day treatment cycles (C). Previous data have shown that palbociclib dose reductions do not affect efficacy. This pooled, post hoc analysis evaluated the frequency of hematologic adverse events (AEs) before and after palbociclib dose reduction in PALOMA-1, PALOMA-2, and PALOMA-3. Methods: This analysis evaluated the frequency of hematologic AEs 30 days before dose reduction and during each subsequent treatment from C1 to C6 among patients who required palbociclib dose reduction. Data were pooled from 3 randomized studies. PALOMA-1 was a phase 2, open-label study of postmenopausal patients untreated for ABC receiving palbociclib plus letrozole or letrozole alone. PALOMA-2 was a phase 3, double-blind study of postmenopausal patients untreated for ABC receiving palbociclib plus letrozole or placebo plus letrozole. PALOMA-3 was a phase 3, double-blind study of pre/perimenopausal or postmenopausal patients, whose disease progressed on prior endocrine therapy, receiving palbociclib plus fulvestrant or placebo plus fulvestrant.

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“…• Приостановить прием до уровня ≥1,0 х 10 9 /л • Возобновить прием со снижением дозы на 1 уровень • При развитии фебрильной нейтропении* приостановить прием до уровня ≥1,0 х 10 9 /л • В случае повторного возникновения -отмена препарата [24]. В объединенном анализе всех исследований PALOMA по безопасности палбоциклиба 3/4 степень АлАТ и АсАТ наблюдалась у 3,3% и 2,3% соответственно [50]. В 1 случае у пациента с прогрессированием метастазов в печени была документирована печеночная недостаточность [20].…”

Section: рисунок 3 циклин D-cdk4/6 Rb сигнальный путьunclassified

Cyclin-dependent kinase inhibitors: efficacy and safety

2019

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Breast Cancer is the most common type of cancer worldwide. Scientific advances and new ways of treating have significantly improved the prognosis of breast cancer in recent decades. The emergence of modern cyclin-dependent kinase (CDK) inhibitors has changed the treatment paradigm for metastatic hormone receptor (HR)-positive breast cancer. In the past four years, the CDK4/6 inhibitors, ribociclib, palbociclib and abemaciclib, received their first FDA approval for the treatment of Hormone Receptor (HR)- positive and Human Epidermal growth factor Receptor 2 (HER2)-negative breast cancer after showing significant improvements in progression-free survival in the PALOMA, MONALEESA and the MONARCH randomized clinical trials, respectively. In the Russian standards for the treatment of metastatic HR positive and HER2-negative breast cancer are included two inhibitors of CDK4/6 – ribociclib, palbociclib. This review summarizes the background of clinical efficacy and potential toxicities seen with the use CDK4/6 inhibitors with endocrine treatment in pre- or postmenopausal women with hormone receptor–positive, HER2-negative advanced or metastatic breast cancer. Despite the similar toxicities, inhibitors of cyclin-dependent kinases differ in their severity and some types of adverse events. Most hematologic abnormalities seen with CDK4/6 inhibitors are not complicated and are adequately managed with standard supportive care and dose adjustments when indicated. This review focuses on the practical management of adverse events associated with CDK4/6 inhibitors.

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Long-term Pooled Safety Analysis of Palbociclib in Combination With Endocrine Therapy for HR+/HER2- Advanced Breast Cancer

Abstract: 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 (NCT02513394).

Cited by 73 publications

References 21 publications

Elevated liver function tests in a patient on palbociclib and fulvestrant

Elevated liver function tests in a patient on palbociclib and fulvestrant

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

Cyclin-dependent kinase inhibitors: efficacy and safety

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