Palbociclib-Induced Liver Failure

Atallah, Rami; Parker, Nathaniel; Hamouche, Karl; Truong, Quoc Van; Dingwall, Megan

doi:10.17161/kjm.v13i1.13628

Cited by 5 publications

(7 citation statements)

References 15 publications

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“…In the PALOMA 3 trial, grade 3 or higher hepatic adverse events included two cases of hepatic failure and one drug-induced liver injury in the palbociclib-fulvestrant arm [ n = 345], while no such events were included in the comparator arm [ n = 172] [ 19 ]. The increased risk of ALI reported here is consistent with imbalances in grade 3/4 ALT elevations in clinical trials, and has been hypothesized in recent reports [ 23 – 26 ]. Additionally, ribociclib and abemaciclib, the two other approved CDK4/6 inhibitors, carry hepatotoxicity warnings in their US package inserts, suggesting hepatotoxicity may be common to this class of medication [ 27 , 28 ].…”

Section: Discussionsupporting

confidence: 91%

Real-world safety of palbociclib in breast cancer patients in the United States: a new user cohort study

et al. 2021

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Background There is limited real-world safety information on palbociclib for treatment of advanced stage HR+/HER2- breast cancer. Methods We conducted a cohort study of breast cancer patients initiating palbociclib and fulvestrant from February 2015 to September 2017 using the HealthCore Integrated Research Database (HIRD), a longitudinal claims database of commercial health plan members in the United States. The historical comparator cohort comprised patients initiating fulvestrant monotherapy from January 2011 to January 2015. Propensity score matching and Cox regression were used to estimate hazard ratios for various safety events. For acute liver injury (ALI), additional analyses and medical record validation were conducted. Results There were 2445 patients who initiated palbociclib including 566 new users of palbociclib-fulvestrant, and 2316 historical new users of fulvestrant monotherapy. Compared to these historical new users of fulvestrant monotherapy, new users of palbociclib-fulvestrant had a greater than 2-fold elevated risk for neutropenia, leukopenia, thrombocytopenia, stomatitis and mucositis, and ALI. Incidence of anemia and QT prolongation were more weakly associated, and incidences of serious infections and pulmonary embolism were similar between groups after propensity score matching. After adjustment for additional ALI risk factors, the elevated risk of ALI in new users of palbociclib-fulvestrant persisted (e.g. primary ALI algorithm hazard ratio (HR) = 3.0, 95% confidence interval (CI) = 1.1–8.4). Conclusions This real-world study found increased risks of several adverse events identified in clinical trials, including neutropenia, leukopenia, and thrombocytopenia, but no increased risk of serious infections or pulmonary embolism when comparing new users of palbociclib-fulvestrant to fulvestrant monotherapy. We observed an increased risk of ALI, extending clinical trial findings of significant imbalances in grade 3/4 elevations of alanine aminotransferase (ALT).

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Section: Discussionsupporting

confidence: 91%

Real-world safety of palbociclib in breast cancer patients in the United States: a new user cohort study

et al. 2021

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Section: Discussionmentioning

confidence: 99%

“…8 A severe case of liver failure was observed for the fulvestrant/palbociclib combination. 9 Increased liver enzymes are common with these agents and are often managed with dose reductions or interruptions. In another analysis, it was stated that 7% Grade 3 toxicity ALAT developed in patients with ribociclib, and the treatment was mostly discontinued in these patients.…”

Section: Discussionmentioning

confidence: 99%

A case report of fulminant hepatitis due to ribociclib with confirmed by liver biopsy in breast cancer

Topcu

Yasin

Shbair

et al. 2021

J Oncol Pharm Pract

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Introduction Breast cancer is the most frequently diagnosed cancer in women worldwide. Ribociclib is now frequently used in the treatment of metastatic hormone-positive and human epidermal growth factor receptor 2 (HER 2)-negative breast cancer. Case Report A 54-year-old woman with breast cancer presented at a clinic in November 2017 with multiple lung and bone metastases. After receiving multiple lines of treatment due to disease progression, ribociclib and fulvestrant were initiated. Grade 4 toxicity was observed due to ribociclib during follow-up, and ribociclib was discontinued permanently. Management & Outcome: Given that liver transaminases and bilirubin elevation persisted despite discontinuation of the treatment, other reasons for liver toxicity were investigated. Abdominal MRI showed no liver metastases, although there was acute hepatitis. A liver biopsy was performed to determine the etiology. The pathology result was compatible with drug-induced acute fulminant toxic hepatitis. After liver biopsy, prednisolone treatment was initiated, after which the laboratory findings normalized. Discussion Although there are reported cases showing improvement in liver enzymes after ribociclib discontinuation, in our case, no recovery from hepatotoxicity was noticed. The treatment was changed to another hormonal pathway therapy option, exemestane. To the best of our knowledge, this is the first case in the literature reporting this rare side effect of ribociclib, which is a liver biopsy-proven fulminant hepatitis.

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“…It was managed with alternative endocrine therapy after an attempt to withhold the medication or by initiating treatment with steroids. Rechallenge with palbociclib led to re-elevation of enzymes up to 10 times the upper limit of the normal range ( 11 – 14 ).…”

Section: Discussionmentioning

confidence: 99%

Palbociclib-induced severe hepatitis: A case study and literature review

Hyppolite

Hilzenrat

2021

CanLivJ

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Palbociclib is a selective and reversible CDK4/6 inhibitor approved for patients presenting with HR+ HER2– locally advanced or metastatic breast cancer. Its adverse effect (AE) is mainly reported on the occurrence of leukopenia and fatigue. Even though palbociclib has an extensive hepatic metabolism, there are rare reports about significant liver toxicity. We present a 61-year-old female with metastatic breast cancer treated with palbociclib and an aromatase inhibitor (letrozole). The patient developed a rare AE of severe acute drug-induced hepatitis but improved dramatically after stopping the palbociclib and receiving treatment with N-acetylcysteine (NAC). The treatment with NAC may be a proof of concept for the mechanism of palbociclib liver injury.

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Palbociclib-Induced Liver Failure

Cited by 5 publications

References 15 publications

Real-world safety of palbociclib in breast cancer patients in the United States: a new user cohort study

Real-world safety of palbociclib in breast cancer patients in the United States: a new user cohort study

A case report of fulminant hepatitis due to ribociclib with confirmed by liver biopsy in breast cancer

Palbociclib-induced severe hepatitis: A case study and literature review

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