Prescription mouthwash prevents painful sores caused by metastatic breast cancer treatment

In the SWISH trial, women diagnosed with hormone receptor-positive breast cancer and treated with exemestane (Aromasin) and everolimus (Afinitor) had fewer and less serious mouth sores when they used a prescription steroid mouthwash during treatment. The results of the study were so impressive that they may lead to this mouthwash becoming a standard part of treatment.

Background

In 2012, the FDA approved the combination of everolimus, an mTOR inhibitor, and exemestane, a hormonal therapy medicine, as treatment for postmenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer. The approval was based on the findings of the BOLERO-2 trial, which showed that women treated with this combination lived longer without disease progression.

Everolimus was the first mTOR inhibitor approved in metastatic breast cancer, and it changed the way this type of breast cancer was treated. But it also caused very painful mouth sores in people who took it.

Two-thirds of BOLERO-2 participants on the exemestane and everolimus combination experienced mouth sores, also called stomatitis. Of those people, half reported feeling at least moderate pain from the sores, classified as sores of grade 2 or higher.

Researchers with the SWISH trial wanted to know if a prescription mouthwash made with a steroid called dexamethasone could prevent the mouth sores caused by everolimus, especially those that caused moderate or severe pain.

Design

SWISH was a phase II study that enrolled 92 postmenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer. All of the participants were scheduled to start taking exemestane and everolimus after the trial started. None started treatment with exemestane or everolimus before the study began.

At the start of the study, all participants watched an educational video about mouth sores and got instructions about good oral hygiene, including information about brushing their teeth at least twice a day and flossing once a day. For 8 weeks, all participants

• Took exemestane and everolimus
• Used a dexamethasone mouthwash for 2 minutes, four times a day
• Kept a daily log of
  • how well they followed the treatment
  • how much oral pain they felt, on a scale of 1-10 and
  • whether they could continue eating their normal diet

The researchers compared the data they collected from the SWISH participants after 8 weeks with data they had from the treatment group in BOLERO-2, who had not been given steroid mouthwash.

SWISH participants could continue using the mouthwash for 8 more weeks if they wished. Once each participant stopped using it, the researchers followed up with them for 28 days to watch for any more side effects.

Results

Of all SWISH participants, 95 percent used the mouthwash 3-4 times a day. The vast majority reported being able to eat their normal diet or a diet with few restrictions.  On average, they reported pain at less than 1 on a scale of 1-10. Researchers used the participants’ logs to assign a grade to participants’ mouth sores.

A lower percentage of SWISH participants experienced mouth sores of any grade in the 8 weeks of the trial than the BOLERO-2 treatment group did in their first 8 weeks:

• Grade 1 mouth sores (mild or no pain):
  • SWISH: 19 percent
  • BOLERO-2: 34 percent
• Grade 2 mouth sores (moderate pain):
  • SWISH: 2 percent
  • BOLERO-2: 20 percent
• Grade 3 mouth sores (severe pain and difficulty eating and drinking):
  • SWISH: Nobody
  • BOLERO-2: 7 percent

Seventy-nine percent of SWISH participants developed no mouth sores, compared to 39 percent of the BOLERO-2 treatment group.

In SWISH and BOLERO-2, most mouth sores appeared within 8 weeks of starting treatment with exemestane and everolimus. In SWISH, when using the mouthwash, the risk of getting any mouth sores during the 8-week period was 61 percent lower than in BOLERO-2, and the risk of getting grade 2 or worse mouth sores was 91 percent lower.

The SWISH participants also were much less likely to stop treatment with exemestane and everolimus because of side effects like mouth sores, high blood sugar and rash. Only 30 percent of people using the mouthwash stopped treatment or got lower doses after having severe side effects, compared to 62 percent of people in the BOLERO-2 group.

Limitations

SWISH was a phase II trial, which means that it was designed to measure how well the mouthwash worked at preventing mouth sores and whether it was safe to use. It also means the researchers enrolled only a small group of participants who were all given mouthwash, rather than enrolling two groups: one to use the mouthwash, and one to go without.

Typically a phase III trial is needed for clinical practice to change. In phase III, researchers recruit hundreds to thousands of people and break them into groups to easily compare how using or not using a new treatment works.

Because SWISH was phase II and the researchers used data from another trial as their control group, it’s less certain whether the two groups experienced the side effects the same way.

What this means for you

It’s exciting that an easily available mouthwash could prevent a common, painful treatment side effect. If you are living with painful mouth sores from everolimus, using it could help you continue treatment, rather than needing to lower your dose or stop treatment because of oral pain.

The SWISH researchers say their results are strong enough to suggest that dexamethasone mouthwash should become standard treatment for anyone taking the everolimus and exemestane combination.

If you are taking everolimus, talk to your oncologist about whether this mouthwash is right for you. Keep in mind that SWISH participants watched a video about mouth sores and were given information about good oral hygiene. This may have helped them do a good job of using the mouthwash regularly. In the real world, it can be hard to make a habit of using mouthwash every day, let alone four times a day, especially if you don’t already use mouthwash. Your doctor or dentist may be able to give you tips on using the mouthwash correctly and keeping your mouth in good health.

Rugo, HS, Seneviratne, L, Beck, JT, et al. Prevention of everolimus-related stomatitis in women with hormone receptor-positive, HER2-negative metastatic breast cancer using dexamethasone mouthwash (SWISH): a single-arm, phase 2 trial. The Lancet Oncology May 2017; Volume 18, No. 5, p654–662; doi: 10.1016/S1470-2045(17)30109-2.