Petros Grivas, MD, PhD, comments on the value of switch maintenance immunotherapy, as seen in the JAVELIN Bladder 100 trial, for the management of urothelial carcinoma.
Petros Grivas, MD, PhD: The big question is: What is the value added by switch-maintenance immunotherapy, based on the JAVELIN Bladder 100 trial? The answer is that patients who get induction chemotherapy in the frontline setting of advanced urothelial cancer may achieve response or stable disease, or they may have progression. For those who achieve response or stable disease, the problem is that those responses or stability of disease is short-lived. So they do not have durable responses, and the median progression-free survival [PFS] from the beginning of chemotherapy is about 7 months. The question has been how can you maintain and sustain this benefit from induction chemotherapy with a regimen, or a modality, of treatment that has less toxicity? You cannot give chemotherapy forever because of cumulative toxicity.
It was from that notion that the JAVELIN Bladder 100 trial was conceived and conducted, and it has changed practices based on the significant overall survival and PFS benefit. A high value has been added because patients who benefit from induction chemotherapy have responses to—or stable disease as a result of—platinum-based chemotherapy in the front line. They can maintain or sustain this benefit by a regimen with less toxicity. Avelumab, in this setting, appears to be well tolerated in the vast majority of patients, with—if I remember correctly—only 7% having grade 3 treatment-related adverse events. About 12% of patients discontinued treatment because of a treatment-emergent adverse event of any cause.
Overall, a high value has been added because you can prolong the life of those patients. They have a significant overall survival benefit, with a hazard ratio of 0.69 in all patients, regardless of PD-L1 expression, and also significant prolongation of PFS. It is important to note that, in this trial, JAVELIN Bladder 100, about 2 of 3 patients on observation by supportive care went on to get subsequent therapy. Despite that, the trial added significant benefit in terms of overall and progression-free survival, and this translates to a change in clinical trial guidelines, FDA approval, EMA [European Medicines Agency] approval, approval in different countries, and the standard of care.
Transcript edited for clarity.