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Safety and efficacy of everolimus (EVE) plus exemestane (EXE) in postmenopausal women with locally advanced or metastatic breast cancer: final results from EVEREXES

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Abstract

Background

This study was conducted to collect clinical safety, tolerability, and efficacy data with the use of everolimus (EVE) combined with exemestane (EXE) in patients with advanced breast cancer (ABC).

Methods

The EVEREXES trial initiated in 2012, provided early access to the first dual blockade treatment with EVE + EXE in patients with HR+, HER2 − ABC in Asia and other emerging growth countries. Postmenopausal women with HR+, HER2 − ABC who had documented recurrence or progression, following a nonsteroidal aromatase inhibitor therapy, were treated with EVE (10 mg/day) + EXE (25 mg/day) orally.

Results

A total of 235 patients received ≥ 1 dose of study medication. At the end of the study, all patients ceased the treatment. Disease progression (66.0%) was the primary reason of discontinuation. The most common AEs (≥ 20%) were stomatitis, decreased appetite, hyperglycemia, rash, aspartate aminotransferase increased, anemia, alanine aminotransferase increased, cough, and fatigue. No new safety concerns were identified in the current study. Median progression-free survival (PFS) in the Asian subset was similar to that of the overall population (9.3 months in both groups). Confirmed overall response rate (ORR) was achieved for 19.6% of the patients. Efficacy of EVE + EXE across subgroups (prior CT, line of treatment, and presence of visceral metastases) was maintained.

Conclusion

The safety and efficacy results from EVEREXES trial are consistent to data previously reported in BOLERO-2. These results support that EVE + EXE could be a viable treatment option for the postmenopausal women with HR+, HER2 − ABC in Asian region.

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Data availability

The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.

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Acknowledgements

The EVEREXES trial (ClinicalTrials.gov identifier NCT03176238). Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals. The authors thank the patients who have enrolled in this study and their families as well as all the participating investigators and their site teams. The authors also thank Arundhati Halder, PhD, and Susmita Bhattacharjee, MSc. Biotechnology, of Novartis Healthcare Pvt Ltd (Hyderabad, India) for providing medical editorial assistance in accordance with the Good Publication Practice (GPP3) guidelines for the preparation of this manuscript.

Funding

The EVEREXES trial was funded by Novartis Pharma AG, Base, Switzerland. Funding for medical editorial support was also provided by Novartis.

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Authors and Affiliations

  1. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

    Young-Hyuck Im

  2. Department of Medical Oncology, Faculty of Medicine, Ege University, Izmir, Turkey

    Bulent Karabulut

  3. Center for Breast Cancer, National Cancer Center, Gyeonggi do, Korea

    Keun Seok Lee

  4. Department of Surgery, Yonsei University Health System, Severance Hospital, Seoul, Korea

    Byeong-Woo Park

  5. Department of Surgical Oncology, HCG Manavata Cancer Centre, Nashik, India

    Aditya Adhav

  6. Department of Medical Oncology, Gaziantep University Medical Faculty, Gaziantep, Turkey

    Havva Yesil Cinkir

  7. King Hussein Cancer Center, Amman, Jordan

    Hikmat Abdel-Razeq

  8. Mackay Memorial Hospital, Taipei, Taiwan

    Yuan-Ching Chang

  9. Hacettepe University Medical Faculty, Ankara, Turkey

    Sercan Aksoy

  10. Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea

    Seock-Ah Im

  11. Department of Surgery, Gangnam Severance Hospital Yonsei University Health System, Seoul, Korea

    Joon Jeong

  12. Kyungpook National University Hospital, Daegu, Korea

    Yeesoo Chae

  13. Novartis Pharma AG, Basel, Switzerland

    James Bowles & Khemaies Slimane

  14. Novartis Asia Pacific Pharmaceuticals Pte Ltd, Singapore, Singapore

    Hongling Xue

  15. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

    Sung-Bae Kim

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Contributions

YHI and SBK contributed to the concept, design, and conduct of the study and analysis and interpretation of the data. BK, KSL, BWP, AA, HYC, HAR, YCC, SA, SAI, JJ, YC, JB, KS, HX contributed to the study conduct. YHI, SBK, JB, KS and HX contributed to the analysis and interpretation of the data. All authors contributed to the development of the manuscript and approved the final manuscript.

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Correspondence to Young-Hyuck Im.

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Conflict of interest

SA has received personal fees from Roche, Merck, Eli Lilly, Abdi Ibrahim AS, BMS, Novartis, Pfizer, Mustafa Nevzat İlaç Sanayii. SBK has received grant from Novartis, Sanofi-Aventis, Kyowa-Kirin Inc, Dongkook Pharm Co, others from Novartis, Personal fees from Astra-Zeneca, Eli Lilly, Enzychem, Dae Hwa Pharmaceutical Co Ltd, ISU Abix, and Daiichi-Sankyo. KSL has received personal fees from Roche, Novartis, Lilly and nonfinancial support from Dong-A Pharm. SAI has received grant from AstraZeneca, Roche, Pfizer, personal fees from Novartis, and others from Amgen, Eisai, Hanmi, and Novartis. JB, KS, and HX are Novartis employees. FR owns Novartis stocks. All other authors declare no conflict of interest.

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Im, YH., Karabulut, B., Lee, K.S. et al. Safety and efficacy of everolimus (EVE) plus exemestane (EXE) in postmenopausal women with locally advanced or metastatic breast cancer: final results from EVEREXES. Breast Cancer Res Treat 188, 77–89 (2021). https://doi.org/10.1007/s10549-021-06173-z

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