SIDEBAR: Dealing with the Toxicity of Everolimus/Exemestane

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While packing a punch in terms of clinical benefit, everolimus plus exemestane can also be a tough pill to swallow for many patients. The management of the potential toxicities associated with this new regimen was addressed at the 2012 Breast Cancer Symposium by Matthew J. Ellis, MB, PhD, of Washington University in St. Louis.

In a poster presentation at the meeting, BOLERO-2 investigators detailed the side-effect profile of the regimen.1 Grade 3/4 adverse events (irrespective of relationship to study drug) were observed in 53% of patients receiving the combination vs 28% of the control arm. The major complaints were stomatitis (59%, all grades; 8%, grade 3), fatigue (37%, all grades; 4%, grade 3), diarrhea (34%, all grades; 2%, grade 3), and rash (39%, all grades; 1%, grade 3).

“Personally, I have been using everolimus for a while, and I have seen every side effect listed on the poster. Many of them have the potential to significantly impact quality of life,” Dr. Ellis noted. “To use everolimus, you must follow your patients weekly, at least for the first 4 to 6 weeks. You must watch for and actively manage side effects in order to keep patients on the drug and realize the benefits of this regimen.”

Specific Reactions

Stomatitis, which is usually of low grade, typically arises less than 1 month after treatment initiation. A prophylactic treatment approach and early recognition is important to minimize its impact. Patient education and precautionary measures may reduce the incidence. Patients should be told to report their first signs of mouth discomfort.

“Clearly, when the patient’s symptoms are moderate to severe, you need to temporarily dose-reduce,” he said. “This side effect often requires considerable holding of the dose and the use of a steroid mouth wash. If from the outset you encourage good dental hygiene and mouth rinses (avoiding those that contain peroxide or alcohol), and provide topical corticosteroids, you can reasonably control most patients.”

Noninfectious pneumonitis occurs in 16% of patients (all grades), characterized by a nonmalignant infiltration of the lungs that may be immunologically mediated.

“I have noticed that quite a lot of patients have subclinical ‘fluffy’ infiltrates at 3 to 6 months. This can look alarming, but patients may be reasonably asymptomatic,” he said. For radiographic findings only, no dose adjustments are required. In the presence of mild symptoms, infection should be ruled out; patients can be treated with corticosteroids and dose interruptions if necessary.

“For patients with any suggestion of shortness of breath, I measure oxygenation with pulse oximetry after they have walked up and down the corridor for 5 minutes,” he added. Serious pneumonitis occurs only in 3% of patients but can be life-threatening, he cautioned.

Dr. Ellis noted that hyperglycemia and rash, while considered part of the toxicity profile, are not particularly a problem, in his experience.

He added that older patients can tolerate treatment almost as well as younger patients, according to an analysis by age.2 “It is reasonable to use the drug in older patients, but with caution,” he said. ■

Disclosure: Dr. Ellis has served in a consulting or advisory role for GlaxoSmithKline, Novartis, and Pfizer, and has received honoraria or research funding from AstraZeneca, Merck, and Novartis.


1. Perez AT: Safety of everolimus in estrogen receptor–positive advanced breast cancer. 2010 Breast Cancer Symposium. Abstract 103. Presented September 14, 2012.

2. Rugo HS, Burris HA, Gnant M, et al: Safety of everolimus for women over age 65 with advanced breast cancer: 12.5-month follow-up of BOLERO-2. 2012 Breast Cancer Symposium. Abstract 104. Presented September 14, 2012.

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