Real-World Performance of Checkpoint Inhibitors Among Platinum-Ineligible Patients With Advanced Bladder Cancer
PracticeUpdate: You recently published a paper that looked at the performance of checkpoint inhibitors in platinum-ineligible patients. What was the rationale for your study?
Dr. Sonpavde: We published a study recently. This was a real world study looking at first-line PD-1 or PD-L1 inhibitor therapy for platinum-ineligible patients, which is different from cisplatin-ineligible patients. Essentially, these are patients that are ineligible for both cisplatin and carboplatin. As we know, the FDA has approved atezolizumab or pembrolizumab monotherapy in platinum-ineligible, so essentially chemotherapy-ineligible patients, in the first-line setting regardless of PD-L1 status of the tumor. We wanted to look at this group a little bit more, because there are not a lot of data out there in this group. This is a new category of patients that was created when the FDA approved these agents in this setting.
PracticeUpdate: How do you define platinum-ineligible patients?
Dr. Sonpavde: That definition remains fuzzy. We're not sure yet on how to define platinum-ineligible patients in general. In patients with poor performance status, PS 3, or with the combination of poor renal function and poor performance status, PS 2, or elderly or other co-morbidities have all been considered to belong to this category. Neuropathy, CHF might also qualify.
At the end of the day, this definition of platinum ineligibility remains unclear and needs to be further studied to refine. We wanted to look at PD-1 or PD-L1 inhibitors in this platinum-ineligible population in real world patients, because there really is not any data out there for these patients.
PracticeUpdate: What did your study find?
Dr. Sonpavde: We collected 79 platinum-ineligible patients. Again, these are platinum-ineligible as defined by the investigator based on some of the criteria I just described. This was a multicenter study, eight institutions, 79 patients. Patients had received the known agents pembrolizumab, atezolizumab, nivolumab or durvalumab in the first line setting. The results showed that the overall response rate of 27.9% and the median overall survival of 45 weeks, was actually quite similar to what we see in the first line cisplatin-ineligible space in unselected patients, regardless of PD-L1 with, let's say pembrolizumab, where you see similar response rates in the 28, 29% range and the median survival a shade under a year.
Adverse Events
The toxicities, though, had a slightly different story. We saw treatment-related toxicities of any grade in 41.8% of patients and grade 3 or higher immune-mediated events in 31.7% of patients. If you just look across studies, the 31.7% grade 3 or higher immune events is higher than what we see, again with the caveat that this is comparing across different studies. Typically, we see grade 3 or higher immune events in 15 to 20% of patients in clinical trials, which of course is a slightly better population than this real world population. The caveat we want to mention is despite that this is a retrospective study, we have to be careful with selecting patients for first-line PD-1 or PD-L1 inhibitor therapy while defining them as platinum-ineligible because patients who are platinum-ineligible might also tolerate toxicities poorly.
PracticeUpdate: What are the implications of your study to clinical practice?
Dr. Sonpavde: We really need to kind of consider these factors when you select patients for first line pembrolizumab or atezolizumab, where they are both approved and would be quite reasonable to consider, but you still need to consider these patients and select them carefully. Remember that we have the JAVELIN Bladder 100 paradigm, which has shown an improvement in survival in a phase 3 trial, which of course starts with the platinum-based chemotherapy, four to six cycles, and patients who are stable or responding disease go on to switch to maintenance avelumab. That paradigm is out there. In the context of that paradigm, we need to consider a first-line PD-1 or PD-L1 inhibitor therapy carefully. It's of course a reasonable option in patients who are PD-L1 high, cisplatin-ineligible, and also is a reasonable option in platinum-ineligible patients. Again, remember the definition [what constitutes these patients] is unclear. We need to select these patients carefully since the toxicities might be somewhat poorly tolerated in this patient population.
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