Cyclin-dependent kinase 4/6 inhibitors and interstitial lung disease in the FDA adverse event reporting system: a pharmacovigilance assessment

Raschi, Emanuel; Fusaroli, Michele; Ardizzoni, Andrea; Poluzzi, Elisabetta; Ponti, Fabrizio De

doi:10.1007/s10549-020-06001-w

Cited by 71 publications

(63 citation statements)

References 35 publications

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“…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].…”

Section: Real-world Evidence Regarding Treatment With Palbociclibmentioning

confidence: 99%

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

et al. 2021

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Breast cancer is the most common type of cancer among women worldwide and in Japan. The majority of breast cancers are hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2‒), and endocrine therapy is an effective therapy for this type of breast cancer. However, recent substantial advances have been made in the management of HR+/HER2‒ advanced breast cancer (ABC) with the advent of targeted therapies, such as cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, resulting in significant improvements in survival outcomes versus endocrine therapy alone. To evaluate the optimal use of palbociclib, a CDK4/6 inhibitor, in HR+/HER2– ABC, this review summarizes clinical trial and real-world data for palbociclib. In addition, current biomarker studies in palbociclib clinical research are reviewed. In Japanese patients, palbociclib was shown to be effective with a manageable safety profile, although differences were observed in the frequency of adverse event and dosing parameters. Current evidence supporting palbociclib as a first-line treatment strategy for patients with HR+/HER2‒ ABC in Asia, and specifically japan, is also discussed.

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Section: Real-world Evidence Regarding Treatment With Palbociclibmentioning

confidence: 99%

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

et al. 2021

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“…Additionally, real‐world evidence revealed that treatment with certain CDK4/6 inhibitors is associated with increased risk for interstitial lung disease (ILD) and venous thromboembolism [14, 15], with the latter associated with shorter PFS and OS [15]. Moreover, a retrospective pharmacovigilance analysis of data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) showed that 0.6% of the 25,503 cases of ILD reported in FAERS were associated with CDK4/6 inhibitors [16].…”

Section: Introductionmentioning

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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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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“…Abnormalities in genes related to surfactant proteins and their release mechanisms are associated with familial pulmonary fibrosis ( Raghu et al, 2011 ). It would be useful to investigate both newly approved drugs and older drugs using data from the Japanese Adverse Drug Event Report (JADER) database and FDA Adverse Event Reporting System (FAERS) for detecting rare adverse events such as ILD ( Fukazawa et al, 2018 ; Raschi et al, 2021 ). Therefore, in the current study, we investigated the potential association between the reporting of ILD and antiandrogen drug usage in clinical practice by conducting a survey of reports in the JADER database, published by the Pharmaceuticals and Medical Devices Agency.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Potential Complications of Interstitial Lung Disease Associated With Antiandrogens Using Data From Databases Reporting Spontaneous Adverse Effects

et al. 2021

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From 2002 to 2018, the number of patients with prostate cancer significantly increased from 679,023 to 1276,106 worldwide. Total prostatectomy (including robot-assisted prostatectomy), radiation therapy, and pharmacological treatment are commonly used to treat prostate cancer. The Chief of the Pharmaceutical Safety Division, that is, the Federation of Pharmaceutical Manufacturers’ Associations of Japan (FPMAJ), recently called for the revision of package inserts for ethical drugs. However, the pathogenesis of interstitial lung disease (ILD), a serious drug-induced adverse effect, remains unclear. Moreover, there have been no large-scale evaluations of potential complications associated with currently used antiandrogens, which are commonly employed to treat prostate cancer. Hence, ILD, as an adverse event, remains poorly understood. Therefore, we conducted a survey of reports in the Japanese Adverse Drug Event Report (JADER) database to investigate the potential association between the reporting of ILD and antiandrogen drug use in clinical practice. The occurrence of ILD was investigated by evaluating the relationship between antiandrogen drug use and ILD. Adverse event signals were detected with reporting odds ratios (RORs), using data from the JADER and FDA Adverse Event Reporting System (FAERS) databases, for the analysis of post-marketing adverse event reports. The JADER was used to examine the time profile of adverse event occurrence for each drug, whereas the FAERS was used to screen cases of unknown adverse events and analyze their trends of occurrence. The analysis of data from both databases revealed the 95% confidence interval lower limits of ROR for bicalutamide and flutamide to be > 1, and adverse event signals were detected following the use of either drug. While caution should be exercised for drugs that are new to the market, we conclude that drugs with similar therapeutic effects that have been in use for a long period should also be re-examined for potential adverse events.

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Cyclin-dependent kinase 4/6 inhibitors and interstitial lung disease in the FDA adverse event reporting system: a pharmacovigilance assessment

Cited by 71 publications

References 35 publications

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

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

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

Evaluation of Potential Complications of Interstitial Lung Disease Associated With Antiandrogens Using Data From Databases Reporting Spontaneous Adverse Effects

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