Early Changes of the Standardized Uptake Values (SUV(max)) Predict the Efficacy of Everolimus-Exemestane in Patients with Hormone Receptor-Positive Metastatic Breast Cancer.

Marianna Sirico, Ottavia Bernocchi, Navid Sobhani, Fabiola Giudici, Silvia P. Corona, Claudio Vernieri, Federico Nichetti, Maria Rosa Cappelletti, Manuela Milani, Carla Strina, Valeria Cervoni, Giuseppina Barbieri, Nicoletta Ziglioli, Martina Dester, Giulia Valeria Bianchi, Filippo De Braud, Daniele Generali

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The mTORC1 inhibitor everolimus has been approved in combination with the aromatase inhibitor exemestane for the treatment of hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (HR+ mBC) progressing on prior therapy with a non-steroidal aromatase inhibitor. To date, no predictive biomarkers of tumor sensitivity/resistance for everolimus-based treatments have been identified. We hypothesized that precocious changes in the Standardized Uptake Volume (∆SUV, as assessed by (18)F-Fluorodeoxyglucosepositron-emission tomography ((18)F-FDG PET/CT), may be a marker of everolimus efficacy. Methods: This was a retrospective study including 31 HR+ HER2- patients treated with everolimus and exemestane in two Italian centers between 2013 and 2018. The objective of the study was to investigate ∆SUV18)F-FDG PET/CT scans were performed at baseline and after three months of treatment. Patients were defined as long responders (LRs) if disease progression occurred at least 10 months after treatment initiation and long survivors (LSs) if death occurred later than 36 months after starting therapy. ROC analysis was used to determine the optimal cut-off values of ∆SUVLRs and LSs from non-LSs. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method. Results: The SUVmax values decreased significantly from baseline to 3 months after therapy (p = 0.003). Dynamic changes of SUVmax (Delta SUV) had a higher accuracy in discriminating long-responders from non-long-responders (AUC = 0.67, Delta SUV cut-off = 28.8 respects to its ability to identify long survivors from no-long survivors (AUC = 0.60, Delta SUV cut-off = 53.8. Patients were divided into groups according to the Delta SUV cut-offs and survival outcomes were evaluated: patients with a decrease of ∆SUV 28.810 months-PFS: 63.2 95 37.9-80.46.7 95 2.7-41.3 p = 0.005). As regard as OS, patients with ∆SUV 53.8SUVtextless 53.836 month-OS: 82.55.9.048). Conclusion: We found two precocious ∆SUV HER2-mBC patients, which would achieve long-term benefit or long-term survival during everolimus-exemestane therapy. These results warrant further validation in prospective studies and should be integrated with molecular biomarkers related to tumor metabolism and mTORC1 signaling.
Original languageEnglish
JournalCancers
Volume12
Issue number11
DOIs
Publication statusPublished - Nov 1 2020

Keywords

  • everolimus
  • metastatic breast cancer
  • ∆SUV 18F-FDG PET/CT
  • predictive biomarker

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