It was an honour to be able to discuss the JAVELIN-100 clinical trial at this year’s ASCO as part of a plenary session. This was a clinical trial looking at patients with metastatic urothelial cancer who had already received platinum-based chemotherapy, so it could have been gemcitabine carboplatinum or gemcitabine cisplatin. Also to qualify for the study those patients had to have at least stable disease as their best response to that prior therapy. It was at this point that patients were enrolled to receive either maintenance avelumab or best supportive care.
So a very straightforward study asking the clear clinical question – should we be giving checkpoint inhibitor early in responding patients after platinum or should we wait until they’ve progressed. The results in the JAVELIN-100 data are clear – the overall survival benefit to the maintenance avelumab when it’s started early rather than best supportive care was clearly seen. Most interesting to me is that the median overall survival in the avelumab group was the highest we’ve ever seen in any urothelial cancer study, even though this is technically the clock started at the second line or the maintenance setting. So this is even better overall survival than we’ve seen in any of the front line urothelial studies.
So I, in my discussion, mentioned that I think this changes how we practise in two ways. One, after a good response to platinum based therapy we should probably consider a maintenance strategy rather than a treatment break. Certainly there are patients who can benefit from a break but there was a similar study done with pembrolizumab, much smaller, that showed similar overall survival when crossover was built into the study, suggesting that if you know you can cross your patient over or get a checkpoint for them after a break that it might be just fine. But overall the data supports a switch maintenance approach here.
The second thing that it really tells us is that we should be starting with platinum based chemotherapy for all patients in whom we can, either carboplatin based or cisplatin based because this sets them up for the best potential overall survival benefit to their subsequent checkpoint inhibitor. We know not all patients who get platinum will be in the categories studied in JAVELIN because about 15% will have primary progression as their best response. That group was not studied and that treatment selection really informs how long the overall survival was in that group. But for 85% of our patients who are likely to have stable disease or a response after platinum, they potentially would benefit most from this switch maintenance approach.