Factors influencing the sequencing of ICI (Immune checkpoint inhibitors) therapy in the second-line setting for urothelial carcinoma.
Petros Grivas, MD, PhD: About 20% of patients in clinical practice received platinum-based chemotherapy in the front line, and they have primary progression. These patients cannot get maintenance therapy because they already had progression—primary progression, on platinum-based chemotherapy. So the question is, what do you do with those patients? Obviously, clinical trials are always the right answer across the board. If you have a clinical trial, I strongly encourage you to consider it across different treatment settings and different spaces.
In the absence of a clinical trial, the 2 options, based on FDA approval in the United States, are checkpoint inhibitors in the second-line space for platinum-refractory disease or erdafitinib, which is an FGFR inhibitor only for patients who have tumors with FGFR2 or FGFR3 mutation or fusion, based on the FDA label. The question of the efficacy between checkpoint inhibitor vs erdafitinib is being addressed in the THOR phase 3 trial, which is randomizing patients with platinum-refractory disease in second-line space—after platinum-based chemotherapy, for example—in pembrolizumab vs erdafitinib. The trial will answer the question.
If you go for a checkpoint inhibitor, there used to be 5 of them, but durvalumab was just withdrawn by the company a few days ago, so there are now 4 options. But based on the totality of the data in the platinum-refractory setting and the phase 3 trials with atezolizumab and pembrolizumab, the only checkpoint inhibitor that has shown overall survival benefit as a primary end point in a phase 3 trial—based on the trial design—is pembrolizumab. This is based on the KEYNOTE-045 trial, which was published in the New England Journal of Medicine by Dr [Joaquim] Bellmunt and colleagues. In a platinum-refractory disease, the second-line options are a clinical trial, a checkpoint inhibitor, or erdafitinib. If you use a checkpoint inhibitor, pembrolizumab has level 1 evidence in this setting.
Transcript edited for clarity.