Whether to use the other agents—nivolumab, avelumab, or durvalumab—they are options. If a provider is very comfortable using those agents, it’s not wrong to give it. It is very reasonable to do. There are community physicians out there who are very comfortable using nivolumab, so it is very reasonable to give it in bladder cancer. If you look at the efficacy rates of these agents, they are very similar; 20% of patients respond and the toxicity rates look similar. Obviously, they haven’t been compared formally in a head-to-head comparison. In the absence of that, it’s a reasonable thing to do. I don’t proactively tell people to only give one drug, because I don’t think that’s necessarily the right way to go about this.
How often do you observe pseudoprogression with immunotherapy agents?
There is about a 20% rate of pseudoprogression in bladder cancer. Knowing when to stop these drugs is a real challenge. Most of the trials allowed patients to remain on past radiographic progression. If they were clinically benefiting from the drug, my practice is to continue these agents in the absence of clear clinical deterioration, which means worsened pain, need for radiation, and in the absence of clear progression on scans where it may be multiple new growing metastases, or metastases in a critical location like in the spinal cord or the renal hilum, or the areas where I am worried that they are going to need a significant surgical or radiological intervention.
If I see progression on more than 2 consecutive scans, that is very likely true progression. That means you should think about switching therapy. The obvious challenge in bladder cancer is we don’t have a lot of [different] therapies. We have only 2 FDA-approved therapies, which are platinum and PD-1/PD-L1 agents, so I try to put patients on a study whenever I can. That should be true for all patients. The decision of when to call it for PD-1 monotherapy is challenging.
There are patients who benefit from platinum therapy. While there is so much enthusiasm and excitement for PD-1 therapy, the response rate is only about 20%. If you’re betting, I tell patients, “You would bet that you’re not going to respond to this drug.” Providers have to be honest about that and realistic about the likelihood of response. There have been cases of patients who had PD-1 treatment, didn’t respond at all and had progression, then received chemotherapy, and had very good responses. Whether that is because they were pretreated with immunotherapy and then got chemotherapy, perhaps—or, perhaps they were just destined to respond to chemotherapy.
It’s a call for better biomarkers. We can look for things like mutational burden, T-cell infiltration, effector T-cell scores, The Cancer Genome Atlas subtypes, and there are a number of other biomarkers that are deeper than PD-L1. Hopefully, that is where the field is moving—not just in bladder cancer, but across all of oncology.
Nogova L, Sequist LV, Perez Garcia JM, et al. Evaluation of BGJ398, a fibroblast growth factor receptor 1-3 kinase inhibitor, in patients with advanced solid tumors harboring genetic alterations in fibroblast growth factor receptors: results of a global phase I, dose-escalation and dose-expansion study. J Clin Oncol. 2017;35(2):157-165. doi: 10.1200/JCO.2016.67.2048.