Research in context
Evidence before this study
We searched PubMed for original research articles in English published between Jan 8, 2006, and Oct 14, 2016, with the terms “breast cancer”, “mTOR inhibitor”, “stomatitis”, and “steroid mouthwash”. We did not identify any phase 2 or 3 trials that investigated the prophylactic use of steroid mouthwash for stomatitis in women who are postmenopausal and treated with everolimus and exemestane for hormone receptor-positive, HER2-negative metastatic breast cancer.
Added value of this study
To our knowledge, this is the first and largest stomatitis prevention study completed that combines therapeutic management with proactive patient engagement to reduce the incidence and severity of stomatitis in patients who are postmenopausal and receiving everolimus and exemestane as treatment for hormone receptor-positive, HER2-negative metastatic breast cancer. Our results show that a commercially available, inexpensive, and well tolerated dexamethasone mouthwash resulted in a more than ten-times reduction in the incidence of grade 2 or higher stomatitis by 8 weeks compared with BOLERO-2 historical controls. Patient-reported outcomes monitoring diet and oral pain further substantiated the efficacy of the dexamethasone mouthwash. The favourable dose intensity for everolimus and exemestane that was recorded in this trial might be a consequence of the reduced incidence of stomatitis, as well as the fact that dexamethasone mouthwash treatment was well tolerated with minimal toxicity.
Implications of all the available evidence
Steroid mouthwash as prophylaxis for everolimus-related stomatitis should be considered as a new standard of oral care for patients who are postmenopausal and receiving everolimus and exemestane for treatment of hormone receptor-positive, HER2-negative metastatic or advanced breast cancer. Several ongoing clinical trials are assessing specific preventive and therapeutic rinses for oral mucositis or stomatitis and might further support a use of steroid-based prophylaxis for everolimus-related stomatitis. This preventative approach might eventually be considered as an important treatment option in many diseases for which everolimus is in active use.