Abstract 3725: Neoadjuvant everolimus as a targeted therapy for early stage breast cancer
Authors: Xu Bing , Williams Casey , Leyland-Jones Brian 
Published: July 2017

Introduction: Everolimus is an oral mTOR inhibitor. It is used for its antitumor effect in breast cancer. This study summarizes the clinical outcomes and noted adverse events from sequencing-derived combination treatments that include everolimus in the neoadjuvant setting.

Material and Methods: To date, 57 breast cancer patients have been enrolled to clinical trial NCT02470715 and treated in the neoadjuvant setting. The data presented here focus specifically on 17 patients that have long enough follow up and that have been treated with everolimus-based combinations. FoundationOne© test and Theralink© assay was used for genomic profiling and proteomic analysis respectively. Clinical outcomes were assessed at the time of surgery. A pathological complete response was defined as the absence of residual disease.

Results: Everolimus was prescribed for the patients in this study based on the findings from their genomic or proteomic testing, targeting PI3K/AKT/mTOR pathway. The evidence for using everolimus in ER+ patients (n=13) includes alterations in PIK3CA (n=9), PTEN (n=3), FGFs (n=2), and phospho-S6 ribosomal protein (Ser235/236). 4E-BP1 (phospho-S65) was targeted in the Her2+ (n=1) patient. PIK3CA (n=2) and PIK3C2B (n=1) presented in the 3 triple negative (TN) patients.

Everolimus and paclitaxel was used in all patients as the backbone combination while trastuzumab was added for Her2+ patients and hormonal therapy was added for ER+ patients. Aromatase inhibitors were used in most of the cases as hormonal therapy in ER+ patients while goserelin was used in 3 cases for premenopausal patients. Pazopanib and trametinib were added to two of the TN patients and palbociclib was added for one ER+ /Her2- patient targeting other alterations.

From the 17 patients (clinical stage I to III) treated with everolimus in the neoadjuvant setting, pathological complete response was achieved in 4 (23%) patients (2 ER+, 1 Her2+ and 1 TN). 65% (n=11) patients had partial response (10 ER+, 1 TN). Only one TN patient did not response to the neoadjuvant treatment.

Over half of the patients (59%) tolerated the treatment well while 6 patients (35%) developed adverse events which resulted in a change of regimen. Grade 3 and above adverse events including mucositis, cough and fever were observed in ER+/Her2- patients who were treated with everolimus + paclitaxel + hormonal therapy. The symptoms were managed by a dose reduction or a period of treatment hold. One ER+/Her2+ patient treated with everolimus + paclitaxel + anastazole + trastuzumab developed a UTI, diarrhea, mucositis and edema after 7 weeks of treatment. Treatment was stopped in this case.

Conclusion: Based upon our findings, everolimus is an effective drug in the neoadjuvant treatment of early stage breast cancer. Even though the numbers are small, our outcomes show significant promise. Adverse events related to the treatment were manageable and did not negatively impact our ability to give the treatment in most cases.

Citation Format: Bing Xu, Casey Williams, Brian Leyland-Jones. Neoadjuvant everolimus as a targeted therapy for early stage breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3725. doi:10.1158/1538-7445.AM2017-3725