Immune Checkpoint Inhibitors in Metastatic Bladder and Other Solid Malignancies: How Long is Enough?

The introduction of T-cell targeted immunomodulators blocking the PD-1 and PD-L1 axis is unquestionably one of the most notable advancements in the treatment of advanced or metastatic solid malignancies, including bladder cancer. Immune checkpoint antibodies are now widely utilized as monotherapies or in combination with other systemic therapies in the first or subsequent lines of treatment in approximately 50 cancer types. Deep and durable responses and long tails of survival curves are hallmarks of patients treated with immune checkpoint inhibitors. However, treatment can have negative impacts, including serious treatment-related side effects as well as a high financial burden to individual patients and the healthcare system. There is increasing data that the benefit of immune checkpoint treatment may persist after treatment is discontinued for reasons other than progressive disease, particularly in patients who have achieved a durable complete response. However, the optimal treatment duration and activity after treatment reinitiation remains undefined and will likely be influenced by disease biology (histology and genomics), treatment (monotherapy or combination therapy), and disease context (depth and duration of response). Well-designed prospective clinical trials and the development and validation of biomarkers that predict outcomes after treatment cessation are needed to move the field forward.