Immunotherapy in Urothelial Cancer: Stop When Achieving a Response, Restart upon Disease Progression

SIMPLE SUMMARY: Immune checkpoint inhibitors (ICI) have dramatically changed the landscape of metastatic urothelial carcinoma (UC). However, optimal duration of treatment with ICI in the metastatic setting remains unclear. On the basis of real-world data from the Netherlands of patients treated with pembrolizumab for metastatic UC, we point out that early discontinuation of ICI seems to be reasonable in a subgroup of patients, especially in patients with responding disease (partial or complete response). It is important to draw attention to this topic and to pursue further efforts to evaluate shorter treatment duration for optimizing patient care and outcomes, but also for keeping healthcare affordable. ABSTRACT: Background: Since there is no clear consensus on optimal treatment duration of PD-(L)1 targeting checkpoint inhibitors in the setting of urothelial cancer (UC) patients, even patients with durable responses are often treated up to 2 years. It is questionable whether this is necessary and whether quality of life improves when treatment is discontinued earlier and restarted when necessary. Methods: We collected available data from locally advanced or metastatic UC patients within the Netherlands between September 2017 and December 2019 treated with first or second-line pembrolizumab, to evaluate treatment duration, reasons for discontinuation, subsequent treatments and survival outcomes. Results: Data were available from 74 patients: 85% (63/74) of patients had a treatment duration of 12 months or shorter, and in seven out of them, treatment was discontinued for another reason than progressive disease. Two patients (3%) had a treatment duration between 12 and 24 months, and eight patients (11%) completed 24 months of treatment. Survival at data cut-off (1 July 2020) with a median follow-up of 35 months was 100% in patients with partial or complete response (6/7 patients) and treatment duration ≤ 12 months, and 100% in patients treated for 24 months. In total, three patients were re-treated with pembrolizumab upon progressive disease during follow-up. Conclusions: In patients who reach partial or complete response during treatment with a PD-(L)1 targeting checkpoint inhibitor, early discontinuation of treatment with pembrolizumab and restart if necessary seems to be reasonable with preserved favorable outcomes. This article should drive further efforts to optimize the treatment duration for patients who respond to treatment with pembrolizumab.