Presence of constipation predicts the therapeutic efficacy of pembrolizumab in metastatic urothelial cancer patients.

Objectives: To study bowel function in urothelial cancer patients treated with pembrolizumab and to assess its association with treatment efficacy.

Methods: This retrospective study was analyzed for patients with metastatic urothelial cancer who received immune checkpoint inhibitor treatment between December 2017 and June 2019 at Nagoya University and affiliated hospitals in Japan. The association between bowel dysfunction (defined as constipation or need for laxatives) and treatment efficacy was investigated.

Results: We retrospectively enrolled 73 patients with metastatic urothelial cancer who received immune checkpoint inhibitor treatment. All patients received pembrolizumab at 200 mg per bodyweight administered intravenously every 3 weeks. Performance status was 0-1 in 58 patients (79.5%), and liver metastasis was detected in 22 patients (30.1%). The median age was 72 years (range 40-89 years). A total of 45 patients had constipation. The median progression-free survival and overall survival from the start of immune checkpoint inhibitor treatment was 4.0 months (95% confidence interval 1.0-17.3) and 6.6 months (95% confidence interval 1.0-18.0), respectively. Patients with constipation had a significantly higher risk of disease progression (P = 0.005). There was no significant association between constipation and overall survival (P = 0.131). However, complete response was observed among two patients treated with immune checkpoint inhibitor, both of whom did not present constipation.

Conclusion: The presence of constipation might be a prognostic factor for urothelial cancer patients undergoing immune checkpoint inhibitor treatment.