bims-cyhorp 2022-08-28 papers

Issue of 2022‒08‒28
four papers selected by
Piotr Okupski

J Oncol Pharm Pract. 2022 Aug 24. 10781552221122057

Elevated transaminases and development of cardiomyopathy in a 32-year-old woman with metastatic breast cancer after treatment with ribociclib followed by palbociclib.

Christina Watts, Karin Nadori.

INTRODUCTION: Cyclin-dependent kinase 4 and 6 inhibitors, ribociclib and palbociclib, are associated with reports of transaminitis and adverse cardiac events.CASE REPORT: The patient is a previously healthy 32-year-old female diagnosed with estrogen receptor-positive, progesterone receptor-positive, and human epidermal growth factor 2 negative metastatic breast cancer. From July to September 2021, the patient was initiated on ribociclib followed by palbociclib for metastatic breast cancer. She subsequently experienced two episodes of transaminitis and was diagnosed with cardiomyopathy.
MANAGEMENT AND OUTCOME: The patient experienced transaminitis 2 weeks after the initiation of ribociclib resulting in discontinuation. When rechallenged with palbociclib, the patient experienced transaminitis within 1 week of initiation, which resulted in discontinuation. Approximately 1 month after palbociclib discontinuation, the patient was diagnosed with congestive heart failure with a left ventricular ejection fraction of 24%.
DISCUSSION: To our knowledge, there are few case studies investigating cyclin-dependent kinase 4 and 6 inhibitor rechallenge following transaminitis. Prior literature suggests that transaminitis with cyclin-dependent kinase 4 and 6 inhibitors is not a class effect, but this case report suggests otherwise. This report presents a rare case of cardiomyopathy and transaminitis following the administration of cyclin-dependent kinase 4 and 6 inhibitors, ribociclib and palbociclib.

Keywords: Case report; cardiomyopathy; cyclin-dependent kinase 4 and 6 inhibitor; metastatic breast cancer; transaminitis

DOI: https://doi.org/10.1177/10781552221122057

Can Liver J. 2021 ;4(4): 433-437

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

Jessie Jean Hyppolite, Nir Hilzenrat.

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 the case of 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.

Keywords: drug-induced liver injury; necro-inflammatory hepatitis; palbociclib

DOI: https://doi.org/10.3138/canlivj-2021-0015

Breast Cancer Res. 2022 Aug 26. 24(1): 57

Evaluation of tumour heterogeneity by 18F-fluoroestradiol PET as a predictive measure in breast cancer patients receiving palbociclib combined with endocrine treatment.

Cheng Liu, Shihui Hu, Xiaoping Xu, Yongping Zhang, Biyun Wang, Shaoli Song, Zhongyi Yang.

BACKGROUND: Predictive biomarkers are needed to identify oestrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER + /HER2-) metastatic breast cancer (MBC) patients who would likely benefit from cyclin-dependent kinase 4 and 6 inhibitors combined with endocrine therapy. Therefore, we performed an exploratory study to evaluate the tumour heterogeneity parameters based on 16α-18F-fluoro-17β-oestradiol (18F-FES)-PET imaging as a potential marker to predict progression-free survival (PFS) in MBC patients receiving palbociclib combined with endocrine therapy.METHODS: Fifty-six ER + MBC patients underwent 18F-FES-PET/CT before the initiation of palbociclib. 18F-FES uptake was quantified and expressed as the standardized uptake value (SUV). Interlesional heterogeneity was qualitatively identified according to the presence or absence of 18F-FES-negative lesions. Intralesional heterogeneity was measured by the SUV-based heterogeneity index (HI = SUVmax/SUVmean). Association with survival was evaluated using the Cox proportional hazards model.
RESULTS: A total of 551 metastatic lesions were found in 56 patients: 507 lesions were identified as 18F-FES-positive, 38 lesions were distributed across 10 patients without 18F-FES uptake, and the remaining 6 were liver lesions. Forty-three patients obtained a clinical benefit, and 13 developed progressive disease (PD) within 24 weeks. Nine out of 10 patients with an 18F-FES-negative site developed PD, and the median PFS was only 2.4 months. Among 46 patients with only 18F-FES-positive lesions, only four patients had PD, and the median PFS was 23.6 months. There were statistically significant differences between the two groups (P < 0.001). For the subgroup of patients with only 18F-FES-positive lesions, low FES-HI patients experienced substantially longer PFS times than those with high FES-HI (26.5 months vs. 16.5 months, P = 0.004).
CONCLUSIONS: 18F-FES-PET may provide a promising method for identifying and selecting candidate ER + /HER2- MBC patients who would most likely benefit from palbociclib combined with endocrine treatment and could serve as a predictive marker for treatment response. Trial registration NCT04992156, Date of registration: August 5, 2021 (retrospectively registered).

Keywords: 18F-FES; Endocrine therapy; Metastatic breast cancer; Palbociclib; Tumour heterogeneity

DOI: https://doi.org/10.1186/s13058-022-01555-7

Cancer Radiother. 2022 Aug 18. pii: S1278-3218(22)00116-0. [Epub ahead of print]

Radiotherapy and CDK inhibitors: Opportunities and risks.

T Brion, L Quéro.

CDK4/6 inhibitors are nowadays commonly used in metastatic HR+/HER2- breast cancer. Herein, we report a literature review regarding the benefits and risks of their combination with radiotherapy. Numerous pre-clinical studies have indeed shown a potential synergistic effect of these treatments in combination with radiotherapy in various types of cancers. On the other hand, some retrospective clinical studies have reported increased acute toxicity in case of digestive or pulmonary irradiation; therefore, it is advisable to discontinue CDK4/6 inhibitors before starting irradiation. Several prospective clinical trials are currently ongoing to assess the feasibility of this combination.

Keywords: Cyclin-dependent kinase 4; Cyclin-dependent kinase 6; Kinase-4 cycline-dépendante; Kinase-6 cycline-dépendante; Radiosensibilisation; Radiosensitization; Radiotherapy; Radiothérapie; Toxicity; Toxicité

DOI: https://doi.org/10.1016/j.canrad.2022.06.017