Everolimus Plus Exemestane in Advanced Breast Cancer: Safety Results of the BALLET Study on Patients Previously Treated Without and with Chemotherapy in the Metastatic Setting

Abstract

With the advent of new targeted agents for advanced or metastatic breast cancer, multiple lines of therapy may be possible, and components of the combined regimens can overlap from one line to another. Thus, it is important to assess even the potential of cumulative and additive toxic effects among the drugs. Previous chemotherapy did not affect the safety profile of the combination regimen of everolimus and exemestane. The continuous monitoring of the safety signals of this drug combination from general clinical practice is important, in particular for stomatitis.

Unfolding the role of the PI3K/AKT/MTOR pathway in male breast cancer: A pragmatic appraisal

“…Current international guidelines issued to guide management of male BC, consider targeted therapy with mTOR inhibitors as well as options guided by PIK3CA mutations in the setting of advanced disease, using the same indications and combinations that are offered to women [ 3 , 27 , 51 ]. Unfortunately, after the BOLERO-2, other prospective trials investigating the efficacy and tolerability of everolimus have also not included male patients [ [52] , [53] , [54] ]. Likewise, even though SOLAR-1 allowed for enrolment of men, the final population only gathered female patients [ 48 ].…”

Co-treatment With Everolimus, an mTOR-Specific Antagonist, or Downregulation of ELK1 Enhances the Sensitivity of Pancreatic Cancer Cells to Genistein

“…In a previous report by Lu et al (2017) a gene set enrichment analysis identified the activation of mTOR signaling in oxaliplatin-treated early passaged cell lines and patient-derived xenografts of colon cancer, and co-treatment of oxaliplatin with an mTOR inhibitor demonstrated an additive effect in the in vitro and in vivo experiments. ELM is a well-established mTOR inhibitor that has been suggested as an ideal combination regimen with chemotherapy for the management of cancers (Li et al, 2016;Generali et al, 2017;Alves et al, 2019). A clinical trial study has also indicated that the combination of ELM and multiagent chemotherapy was well-tolerated in patients with acute lymphoblastic leukemia (Place et al, 2018).…”

On-Target Side Effects of Targeted Therapeutics of Cancer

“…Interestingly, de frequency of the incidence of pneumonitis varies in different clinical trials, despite it is considered as an "on target" side effect (45). For example, in breast cancer clinical trials the incidence of pneumonitis was found to be 7.6% compared to pancreatic neuroendocrine clinical trials in which the frequency of pneumonitis was much higher, 17% (48,49). There are also available reports on a much higher incidence, reaching 49% (31).…”