Abstract P3-14-09: Hyperglycemia secondary to everolimus is associated with a prognosis improvement in hormone-sensitive metastatic breast cancer. A retrospective analysis
Authors: Sandiego S , Algarra MA , Aguilar HA , Álvarez P , Guerrero A , Gavilà J , Soriano V , Blanch S , Guillem V , Ruiz A 
Published: May 2019

Introduction

The Everolimus and Exemestane combination improves PFS (progression-free survival) in patients with metastatic hormone-sensitive breast cancer pre-treated with aromatase inhibitors (BOLERO-2). However, such combination is associated with an increase in the rate of adverse events compared to monotherapy with Exemestane.

Patients and Methods

We selected female patients diagnosed in our center from hormone-sensitive metastatic breast cancer who were treated with the combination of Everolimus 10mg plus Exemestane 25mg between January 2012 and June 2018 (n=84). In these patients, we analyzed the number and grade of adverse events, as well as the correlation between each adverse event and the PFS.

Results

As patient characteristics, median age was 61 years old. 39.3% had bone metastases at the diagnosis of metastatic disease, 14,3% had visceral metastases and 46,4% had visceral and bone metastases. They had received a median of 2 treatments for advanced disease (including chemotherapy or hormonotherapy) previous to Exemestane and Everolimus, and at least 2 months of the combination treatment. Median SLP was 6 months.

AE´s in IVO patients (n=84) AE´sHyperglycemia30 (35.7%) - (0% G3/4)Hypercholesterolemia27 (32.1%) - (0% G3/4)Hypertriglyceridemia20 (23.8%) - (0% G3/4)Mucositis41 (48.8%) - (17% G3/4)Blood pressure4 (4.8%) - (0% G3/4)Neumonitis10 (11,9%) - (40% G3/4)Fatigue37 (44%) - (19% G3/4)Rash16 (19%) - (0% G3/4)

Once we had collected the frequency of AE, we tried to see if there was a correlation between the apparition of any AE and an impact in PFS.

 PFS (months)PFS (months) AEYESNOP-VALUEHyperglycemia12,71 (8,7-15,8)7,52 (5,4-8,2)0,008Hypercholesterolemia10,4 (6,9-13,8)8,2 (6,3-10,1)0,18Hypertriglyceridemia7,3 (4,9-9,8)9,3 (7,2-11,4)0,323Mucositis10,3 (7,6-12,94)7,5 (5,4-9,5)0,064Neumonitis11,8 (7,3-16,3)8,3 (6,5-10,2)0,291Rash11,6 (7,6-15,6)8,2 (6,3-10,02)0,124

In the univariate analysis, we see a statisticaly significative correlation between the presence of hyperglycemia and an improvement in PFS.

In the multivariate analysis using all AE´s, impact of hyperglycemia in SLP remained statisticaly significative (SLP for variable Hyperglycemia has a p-value of 0,014 and 0,531 Exp(B)

Conclusions

In our experience, mucositis is the most frequent AE in patients treated with the combination, followed by fatigue and hyperglycemia. Moreover, it seems to be a correlation between the apparition of hyperglycemia and better PFS. It´s well known that mTORc1 (target of Everolimus) has an important role in glycolisis: maybe the development of hyperglycemia is an indirect data from a better target inhibition. Analysis between other biological and tumor factors and their impact on survival is ongoing.

Citation Format: Sandiego S, Algarra MA, Aguilar HA, Álvarez P, Guerrero A, Gavilà J, Soriano V, Blanch S, Guillem V, Ruiz A. Hyperglycemia secondary to everolimus is associated with a prognosis improvement in hormone-sensitive metastatic breast cancer. A retrospective analysis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-14-09.