BOLERO-2 Trial: Everolimus in Metastatic Breast Cancer

Panelists: Adam M. Brufsky, MD, PhD, University of Pittsburgh; Sara Hurvitz, MD, UCLA;
Joyce A. O'Shaughnessy, MD, US Oncology; Edith A. Perez, MD, Mayo Clinic; Hope S. Rugo, MD, UCSF;
Andrew D. Seidman, MD, MSKCC
Published Online: Thursday, June 13, 2013
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Interest in treatment with novel combinations of targeted agents and hormonal therapies in hormone receptor-positive breast cancer caused the establishment of several unique clinical trials, including BOLERO-2, suggests moderator Adam M. Brufsky, MD, PhD.

Initially, some researchers did not believe the combination of an mTOR inhibitor and hormonal therapy would prove to be effective. This skepticism was partially based on earlier research into the mTOR inhibitor temsirolimus, which did not demonstrate efficacy in this space, Brufsky suggests. However, since this initial setback, the treatment paradigm changed to include more exposure to aromatase inhibitors (AIs) and longer durations of treatment with hormonal therapies, explains Hope S. Rugo, MD. Also, the mTOR inhibitor dose in initial trials may not have been correct, based on levels of stomatitis, a common side effect of mTOR inhibition.

Initially, research into the mTOR inhibitor everolimus was undertaken in the neoadjuvant setting, looking for a potential biomarker, explains Rugo. In this trial, a great deal of information was uncovered about treatment with everolimus, including the occurrence of interstitial pneumonitis and other side effects. Additionally, the trial demonstrated a slight clinical benefit and a significant drop in Ki67.

The rationale to explore mTOR inhibition in the metastatic setting stemmed from information on the PI3K pathway and the increased mutational burden in advanced disease. The phase III BOLERO-2 trial was undertaken to explore this rationale further. In the trial, patients were randomized 2:1 to receive exemestane plus everolimus or exemestane and placebo. Most patients enrolled were chemotherapy naive and a large amount had visceral disease, which generally indicates the need for treatment with chemotherapy, Rugo notes.

In the trial, there was a large difference in progression-free survival favoring treatment with everolimus. Interestingly, Rugo explains, the progression free survival benefit was less pronounced by local assessment than by independent central evaluation, which is not generally the case.

Examining the toxicity profile, the main concern that has been raised was the occurrence of stomatitis. In general, Rugo notes, grade 3 stomatitis occurred in 8% of patients. However, Joyce A. O'Shaughnessy, MD, recommends the utilization of a steroid mouthwash as a preventive option. This approach seems to be largely effective in most patients, Rugo and O'Shaughnessy agree.
View More From This Discussion
Episode 1 Introduction and Exploration of Fulvestrant in Breast Cancer
Episode 2 Combination of Anastrozole and Fulvestrant in MBC
Episode 3 BOLERO-2 Trial: Everolimus in Metastatic Breast Cancer
Episode 4 Management of mTOR Inhibitor Side Effects in Breast Cancer
Episode 5 EMILIA Trial: T-DM1 in Metastatic Breast Cancer
Episode 6 Frontline T-DM1 in HER2+ Metastatic Breast Cancer
Episode 7 CLEOPATRA Trial: Frontline Pertuzumab for HER2+ MBC
Episode 8 MA.31 Trial: Taxane With Lapatinib or Trastuzumab
Episode 9 Treatment With Eribulin in Metastatic Breast Cancer
Episode 10 Case Study: Treating HER2-Positive MBC, Part I
Episode 11 Case Study: Treating HER2-Positive MBC, Part II
Episode 12 Paclitaxel With Pertuzumab Plus Trastuzumab in MBC
Episode 13 Case Study: Treating HR+ and HER2- Breast Cancer
Episode 14 Managing Bone Health in Metastatic Breast Cancer
Episode 15 Surgical Removal of Primary Tumors in Stage IV MBC
Episode 16 Case Study: Metastatic Triple-Negative Breast Cancer
Episode 17 Personalized Medicine in Triple-Negative Breast Cancer
Episode 18 Conclusion and Final Thoughts on Managing Breast Cancer
Expert Panelists
Dr Adam Brufsky

Adam M. Brufsky, MD, PhD

Professor of Medicine, University of Pittsburgh
Medical Director of the Women’s Cancer Center
at Magee-Womens Hospital of UPMC
and the University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania

Sara Hurvitz, MD

Assistant Professor & Director,
Hematology/Oncology Breast Cancer Program, UCLA's Jonsson Comprehensive Cancer Center, Los Angeles, California

Joyce A. O’Shaughnessy, MD

Co-Director, Breast Cancer Research
Baylor Charles A. Sammons Cancer Center
Texas Oncology, PA/US Oncology,
Dallas, Texas

Edith A. Perez, MD

Deputy Director of the Mayo Clinic Cancer Center, Director of the Breast Cancer Translational Genomics Program and the Breast Program at Mayo Clinic,
Jacksonville, Florida

Hope S. Rugo, MD

Professor of Medicine and Director of the Breast Oncology, Clinical Trials, and Education Program, University of California San Francisco Comprehensive Cancer Center, San Francisco, California

Andrew D. Seidman, MD

Professor of Medicine, Weill Cornell Cancer Center, Attending Physician at Memorial Sloan Kettering Cancer Center,
New York, New York
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