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Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a treatment-limiting and debilitating neurotoxicity of many commonly used anti-cancer agents, including paclitaxel. The objective of this study was to confirm the previously found inverse association between pre-treatment blood concentrations of histidine and CIPN occurrence and examine relationships of other amino acids with CIPN severity., Methods: Pre-treatment levels of 20 amino acid concentrations were measured via a targeted mass spectrometry assay in banked serum from the SWOG S0221 (NCT00070564) trial of patients with early-stage breast cancer receiving paclitaxel. The associations between amino acid levels and CIPN occurrence or severity were tested in regression analysis adjusted for paclitaxel schedule, age, self-reported race, and body mass index with Bonferroni correction for multiple comparisons. The network of metabolic pathways of amino acids was analyzed using over-representation analysis in MetaboAnalyst. The partial correlation network of amino acids was evaluated using a debiased sparse partial correlation algorithm and Cytoscape., Results: In the primary analysis, histidine concentration was not associated with CIPN occurrence (odds ratio (OR) = 0.97 [0.83, 1.13], p = 0.72). In a secondary analysis, no amino acid was associated with CIPN occurrence (all p > 0.0025). Higher concentrations of four amino acids, glutamate (β = 0.58 [0.23, 0.93], p = 0.001), phenylalanine (β = 0.54 [0.19, 0.89], p = 0.002), tyrosine (β = 0.57 [0.23, 0.91], p = 0.001), and valine (β = 0.58 [0.24, 0.92], p = 0.001) were associated with more severe CIPN, but none of these associations retained significance after adjustment. In the over-representation analysis, no amino acid metabolic pathways were significantly enriched (all FDR > 0.05). In the network of enriched pathways, glutamate metabolism had the highest centrality., Conclusions: This analysis showed that pre-treatment serum amino acid concentrations are not strongly predictive of CIPN severity. Future prospectively designed studies that assess non-amino acid metabolomics predictors are encouraged., Competing Interests: Competing Interests: This study was supported in party by Amgen, Inc. The authors declare no relevant conflicts of interest.

Background: CDK4/6 inhibitors (CDK4/6i), in combination with aromatase inhibitors, are United States Food and Drug Administration-approved for the treatment of hormone receptor-positive (HR + )/human epidermal growth factor receptor 2-negative (HER2 - ) metastatic breast cancer (MBC). The effectiveness of continuing them beyond first disease progression (PD) is currently unknown. This retrospective study evaluated the impact of the continuation of CDK4/6i beyond first PD in HR + /HER2 - MBC using real-world experience., Patients and Methods: A single-institution retrospective review of patients with HR + MBC who received CDK4/6is from 2015 to 2018 and where CDK4/6is were continued beyond first PD. The primary outcome was progression-free survival (PFS) after initial PD on CDK4/6i therapy., Results: Thirty women with HR + /HER2 - MBC met eligibility criteria. Patients were identified from a prospective database of patients at the Cleveland Clinic Foundation who were prescribed CDK4/6is. The median age and follow-up duration were 47.5 years and 27 months, respectively. Most patients received palbociclib (PA)/letrozole as initial therapy (67%), followed by PA/fulvestrant (23%), and PA/other aromatase inhibitor (20%), and abemaciclib with either fulvestrant or letrozole (6%). As of January 31, 2019, 25 (83.3%) patients were still alive, and 19 (63%) patients had progressed. The estimated median PFS for continued CDK4/6i use beyond the first PD was 11.8 months (95% confidence interval, 5.34-13.13 months)., Conclusions: Among a small cohort of patients with HR + MBC in a non-clinical trial setting, continuation of CDK4/6i-endocrine treatment post initial PD was associated with a median PFS of about 12 months. Formal randomized clinical trials evaluating the continuation of CDK4/6is beyond the first PD are currently ongoing and will provide more answers to this important clinical question., (Copyright © 2020 Elsevier Inc. All rights reserved.)