A study of women treated with the mTOR inhibitor everolimus (Afinitor) plus exemestane for their advanced breast cancer found that daily use of a steroid-based mouthwash markedly decreased the incidence and severity of stomatitis, and the researchers recommend that this preventive regimen become standard of care in this setting. The findings were reported at the 2016 ASCO Annual Meeting.
The trial, known as SWISH, found that after 8 weeks of using the mouthwash 4 times daily, incidence of grade ≥2 stomatitis was 2.4%, and stomatitis of all grades was 21.2%, compared with 33% and 67% of patients, respectively, in the comparator BOLERO-2 trial who did not use the mouthwash. That trial examined efficacy of the everolimus/exemestane (EVE/EXE) combination in patients with HR-positive, HER2-negative metastatic disease.
Lead investigator Hope S. Rugo, MD, described the SWISH findings as “very encouraging,” adding that the women who used the mouthwash tolerated it very well.
“There was a lot of concern about quality of life in these [BOLERO-2] patients. The other toxicities from everolimus are relatively easy to manage or uncommon,” explained Rugo in an interview at ASCO. Rugo is professor of Medicine and director of the Breast Oncology Clinical Trials Program at the UCSF Hellen Diller Family Comprehensive Cancer Center.
“Stomatitis is really the big issue, and almost all stomatitis occurs in the first 8 weeks.”
Against that backdrop, investigators sought to determine whether prophylactic use of a commercially available, alcohol-free, steroid-based mouthwash would prevent or ease the severity of this painful, treatment-related adverse event which can interfere with eating and lead to treatment disruptions.
The multicenter, single-arm, phase II SWISH prevention trial followed 86 postmenopausal women receiving the EVE/EXE combination daily for their HR+, HER2- advanced breast cancer. Women with existing stomatitis, oral mucositis, or mouth ulcers were excluded from the study.
Participants were instructed to use 10 mL of a commercially available, alcohol-free dexamethasone oral solution (0.5 mg/5mL; Roxane Pharmaceuticals) 4 times daily, and to swish it for 2 minutes before spitting it out. They were given a timer and instructed to take nothing by mouth for 1 hour after administration.
The mouthwash regimen was begun on day 1 of each 28-day EVE/EXE treatment cycle, for a minimum of 2 cycles. Participants filled out daily diaries to record their dietary intake and oral pain levels and also received education about the importance of good oral hygiene, including proper teeth brushing, flossing, and continuing their routine dental care.
Researchers reported that preventive use of the dexamethasone mouthwash “resulted in a greater than 10-fold reduction in the incidence of grade ≥2 stomatitis compared with BOLERO-2 patients.” Of the 2 patients in the mouthwash group who developed ≥2 stomatitis, the adverse event resolved to grade ≤1 after 11 days in 1 patient and 15 days in the other.
“We were really encouraged by this, and I think it is a new standard of care for patients who are taking everolimus,” said Rugo. “If you use the steroid mouthwash up front, you can prevent significant stomatitis—reducing the rate, and also the severity.”
Laura Guerra, RN, CCRC, Research Department Manager with of Oncology Consultants in Houston, Texas, explained that stomatitis can be very debilitating for patients who experience it. She noted in an interview with OncLive
at the ASCO meeting that the stomatitis seen in the BOLERO-2 trial “was different from what we usually see, in that the sores tended to be deep sores with some pain. The condition can affect not only nutrition, but also interfere with delivery of the medication, as patients have to swallow it.”
She noted that before this intervention, many patients on the BOLERO-2 trial had to interrupt their treatment due to stomatitis, and thus not get the full benefit of their regimen.
“If [we] can minimize or reduce these toxicities, patients will be more compliant with taking their anticancer medications, and it’s well known that when patients take their medication the way they’re supposed to, they’ll have better outcomes.”
For patients who continue to have clinical efficacy with everolimus, Rugo said that they can use the mouthwash as needed. If the mouth sores stop or taper off, they can stop using the mouthwash, but if they recur, patients can resume using the mouthwash. “A lot of our patients did continue with it,” she added, with some reducing the frequency of the mouthwash, for example, to 3 times per day.
“What that does for patients is to make the treatment more tolerable, regardless of what efficacy they eventually achieve. That’s our goal in the treatment of breast cancer, and certainly in the treatment of metastatic breast disease—to achieve the therapeutic efficacy with less toxicity.”
Rugo said that the dexamethasone mouthwash represents a very cost-effective option to avoid this often dose-limiting toxicity. “I do think this is ready to integrate into practice now.”
Rugo HS, Seneviratne L, Beck JT, et al. Prevention of everolimus/exemestane (EVE/EXE) stomatitis in postmenopausal (PM) women with hormone receptor-positive (HR+) metastatic breast cancer (MBC) using a dexamethasone-based mouthwash (MW): Results of the SWISH trial. 2016; J Clin Oncol. 34(suppl; abstr 525).