What proportion of your patients receiving everolimus require dose adjustments for toxicity?
Kimberly L Blackwell, MD | |
Professor of Medicine Director, Breast Cancer Program Duke Cancer Institute Durham, North Carolina |
I would estimate that about two thirds of patients receiving everolimus require dose adjustments for mucositis. I do not use prophylactic measures to prevent mucositis associated with everolimus because we have no data that any of them are effective.
I have administered everolimus to 50 to 60 patients with breast cancer, of whom 2 developed pneumonitis. It’s important to not only recognize this toxicity but also develop a rapport with your pulmonologist because the pneumonitis can be severe. If you don’t stop the drug early enough, it can worsen. A bronchoscopy can be informative, because the radiologic appearance can appear as lymphangitic spread. The treating clinician needs to have a high level of suspicion of pneumonitis, especially for patients who have had no preexisting lung metastases who develop haziness in their lungs. Everolimus needs to be stopped in these cases until the condition resolves.
Lisa A Carey, MD | |
Richardson and Marilyn Jacobs Preyer Distinguished Professor for Breast Cancer Research Chief, Division of Hematology and Oncology Physician-in-Chief North Carolina Cancer Hospital Associate Director for Clinical Research Lineberger Comprehensive Cancer Center Chapel Hill, North Carolina |
I would estimate that about 40% to 50% of patients who receive everolimus require dose modifications or interruptions because of mucositis. I have patients decrease the dose from 10 mg to 7 mg or even 5 mg. That option is perfectly reasonable if the disease can still be controlled at the lower dose. I’ve starting using steroid-based mouthwashes preemptively.
I am encouraged by the fact that we’re now seeing much better control of everolimus-related side effects. Recently, we’ve been quicker to intervene and we’re observing less toxicity as a result. Older patients find it more difficult to tolerate everolimus. So early prophylaxis for these patients should be considered.
Julie R Gralow, MD | |
Professor, Medical Oncology Jill Bennett Endowed Professorship in Breast Cancer University of Washington School of Medicine Director, Breast Medical Oncology University of Washington School of Medicine/Seattle Cancer Care Alliance Member, Clinical Research Division Fred Hutchinson Cancer Research Center Seattle, Washington |
I would say that about 40% to 50% of patients receiving everolimus require dose adjustments for toxicity. I’ve treated about 30 cases of breast cancer with everolimus. Of these patients, about half developed mucositis that required a dose modification. We use prophylactic measures, which include a steroid mouthwash to prevent everolimus-associated mucositis.
Everolimus is not as well tolerated as endocrine therapy, even in the patients who don’t require a dose adjustment. Patients experience a lot of fatigue and simply don’t feel well.
Three or 4 of the patients to whom I’ve administered everolimus developed pneumonitis a few weeks after starting the drug. In 2 patients it was severe enough to require hospitalization.
Clifford Hudis, MD | |
Chief, Breast Cancer Medicine Service Solid Tumor Division Department of Medicine Memorial Sloan-Kettering Cancer Center Professor of Medicine Weill Cornell Medical College New York, New York |
More than half of the patients to whom I’ve administered everolimus have required dose adjustments for toxicity. In my experience most patients who receive everolimus develop mucositis. Our typical strategy to deal with the mucositis is to follow the recommendations of the package insert and stop therapy or reduce the dose by 50% and then resume therapy. I’ve administered everolimus to about 12 patients with breast cancer. One of these patients developed pneumonitis.
Ian E Krop, MD, PhD | |
Associate Physician Dana-Farber Cancer Institute Assistant Professor of Medicine Harvard Medical School Boston, Massachusetts |
I’ve treated about 15 cases of breast cancer with everolimus. I would estimate that half these patients have required a dose reduction, usually due to mucositis. I do not employ preemptive measures to prevent mucositis. Once patients develop mucositis I stop the drug, allow the patient to recover and reduce the dose. Steroid-containing mouthwashes have been tried, but I think the biggest take-home message is that everolimus has to be stopped early and the dose has to be reduced.
In terms of other problems with everolimus, sometimes fatigue can also be a significant limitation for these patients. I have not observed pneumonitis in any patients yet, but this is something we need to be vigilant about.
Kathy D Miller, MD | |
Co-Director, IU Simon Cancer Center Breast Cancer Team Ballvé Lantero Scholar in Oncology Associate Professor of Medicine Department of Personalized Medicine Division of Hematology/Oncology The Indiana University Melvin and Bren Simon Cancer Center Indianapolis, Indiana |
I have administered everolimus to about 20 patients with breast cancer, and about 50% of these patients have required a dose adjustment due to toxicity. Two patients developed pneumonitis. Of the patients who developed mucositis, about half required dose interruption or discontinuation. I do not use any prophylactic measures to treat everolimus-related mucositis. Close attention to nursing intervention and patient education are important in minimizing toxicity. We have recently started patients at a lower dose with a plan to increase the dose in those who are faring well rather than the other way around.
Joyce O’Shaughnessy, MD | |
Co-Director Breast Cancer Research Program Baylor-Charles A Sammons Cancer Center Texas Oncology US Oncology Dallas, Texas |
I would estimate that about 25% of patients require a dose adjustment for toxicity. We use a mouthwash with hydrocortisone and ask patients to swish and spit 4 times a day starting on day 1 of everolimus treatment. Starting the mouthwash from the first day of treatment is important and works well as a prophylactic measure to prevent mucositis. I’ve administered everolimus to 24 patients. Since I’ve started recommending the mouthwash I’ve not had to modify the dose of everolimus in any patient due to mucositis.
Pneumonitis is a late-developing toxicity for which we do not have any known prophylactic strategies. One cannot predict which patients will develop it, and in my experience the only way to manage it is to stop treatment with everolimus. Fatigue can be a problem in the first 2 to 3 months and improves with time. I’ve had to dose reduce for myelosuppression in 1 patient.
Hope S Rugo, MD | |
Professor of Medicine Director Breast Oncology and Clinical Trials Education University of California, San Francisco Helen Diller Family Comprehensive Cancer Center San Francisco, California |
The minority of patients to whom I have administered everolimus have required a dose adjustment because I use a steroid mouthwash to prevent mucositis. Generally it is the older patients who require dose reductions. I’ve administered everolimus to about 30 patients as part of the BOLERO-2 trial. Less than 5% of patients developed mucositis requiring a dose interruption. Mucositis is usually seen in the first 6 weeks or so, based on the BOLERO-2 study. Patients who have poorly controlled glucose are more likely to have a problem with it.
Interstitial pneumonitis occurs rarely. I haven’t had a big problem with everolimus-associated toxicity because of my management strategies. The patients who I believe have the hardest time with fatigue, anorexia and weight loss are those who have been receiving the drug for a long period of time. In that situation, I will often interrupt or dose reduce. Overall, I would say that patient and physician education and preemptive measures to reduce toxicity are effective in improving tolerability.