Two phase III clinical studies of cevimeline for post-radiation xerostomia in patients with head and neck cancer

Abstract

5503 Background: Xerostomia is a frequent debilitating complication of head and neck cancer radiotherapy. Morbidities include dental caries, oral infections, and impaired quality of life. Methods: Two multicenter double-blind trials were conducted to assess the efficacy and safety of cevimeline in the treatment of radiation-induced xerostomia. Each trial enrolled subjects ≥18 years of age with head and neck cancer who had received >4000 cGy of radiation ≥4 months before entry and had clinically significant salivary gland dysfunction. Subjects were randomized to cevimeline 30 mg TID or placebo for 12 weeks, with escalation to 45 mg TID or placebo equivalent at 6 weeks if no improvement was reported. Subjects experiencing side effects after dose escalation could de-escalate to 30 mg TID. The primary efficacy endpoint was global evaluation of oral dryness, with a secondary endpoint being change in unstimulated salivary flow. Results: A total of 570 subjects (284 in the 003 and 286 in the 004 study) were randomized. In the final (visit 5) global evaluation of dry mouth in the intention-to-treat (ITT) analysis, improvement was reported by a greater percentage of subjects treated with cevimeline compared with placebo recipients (47.4% vs 33.3%, P=0.0162) in the 003 study; differences between groups were significant at visits 3 through 5 (P≤0.0162). Differences of global evaluation of oral dryness between the treatment and placebo groups were not statistically significant in the 004 study, although a high placebo response rate was observed (48.9% vs 47.6%, P=0.9565). In both studies, cevimeline-treated patients had significantly greater mean increases in unstimulated salivary flow than placebo treated patients at the final visit (ITT, P=0.0093 [003] and P=0.0215 [004]). Cevimeline was well tolerated in both studies. Adverse event frequency was comparable in the placebo and cevimeline groups, with the exception of increased sweating in the cevimeline group. Conclusions: Cevimeline 30 to 45 mg TID increased mean unstimulated salivary flow in both studies and in one study improved subjective dry mouth sensation in subjects with xerostomia following radiation therapy for head and neck cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Daiichi