Checkpoint Inhibitors in Advanced Bladder Cancer - Episode 5

Monitoring for Treatment Response in Advanced Bladder Cancer


Daniel J. George, MD: Right now, where we’re most commonly using our cisplatin-based chemotherapy is in patients in the neoadjuvant setting. So, in patients who present to us with muscle-invasive disease, many of whom may have clinically T3, T4 lesions, we’ll treat those patients with cisplatin-based chemotherapy with the hopes that they’re still potentially resectable. Or perhaps they have more what appears to be organ-confined muscle-invasive disease and we’ll be treating them more for a pathologic complete response rate.

What we see in that population is a mix. We’ll see, on average, somewhere around 20% to 30% of patients get a pathologic complete response. Majority of patients will have residual disease. For many of those patients who have really locally advanced disease or nodal disease, the complete response rates are low. Really what we’re doing there is essentially a debulking, follow-up. Many of those patients are going to relapse within the first year, certainly within the first 2 years, following chemotherapy. So, if they’re going to relapse, that’s when we see our relapses. On average, when we’re treating patients in the metastatic setting with a frontline cisplatin-based chemotherapy, we see response rates somewhere around 50%. Those are usually partial responses, but occasionally, we can see complete responses, particularly in patients with lung-only or lymph node-only disease.

For patients who are getting a partial response, their time to progression following the chemotherapy is generally short, about 4 to 6 months. So, for me, when I’m treating somebody with platinum-based chemotherapy, if it’s in the neoadjuvant setting, we’re quickly moving on to surgery. There really isn’t time to reassess. It’s typically 4 cycles of chemotherapy and then on to surgery. For patients who I’m treating metastatic disease, I’m assessing after about 3 cycles of therapy. About half our patients are showing some level of response, another, maybe, quarter patients with stable disease. About 25% of patients will be blasting through that, and that’s the group of patients we want to pick up early and get on to checkpoint inhibitors.

For those who are stable or responding, we’re able to complete maybe 6 cycles of chemotherapy, but their time to relapse following that is going to be short. So that’s a group of patients we’re monitoring closely for. Lastly, there is a group of patients who get a complete response to chemotherapy or maybe a really good partial response that will last a year or more. Historically, those are patients whom we can rechallenge with platinum chemotherapy and see response to again. So, I don’t want to forget about that population. Platinum chemotherapy is still a good agent. I don’t want to say everything is checkpoints. There’s a role, for sure, for cisplatin-based chemotherapy, but it has to be taken into context. The majority, 75% of these patients, are going to either have transient responses or no response at all, and we’ve got to be prepared to make that quick switch to immunotherapy.

When I’m using the checkpoint inhibitors—PD-1, PD-L1 inhibitors—in that setting, I’m going to be a little bit more flexible in making a thumbs up- or thumbs down-decision based upon a single time point and scan, particularly if there’s not clinical progression associated with it and knowing that I chose that checkpoint inhibitor as a frontline therapy over chemotherapy for a reason. Either they’re platinum ineligible, or I don’t feel they’re very good candidates for carboplatinum-based chemotherapy. So, my threshold for continuing through a mixed response is pretty high. But if patients have real clinical progression, if there’s clear visceral progression going on, and new sites of disease, those are the patients we do want to switch. There are a number of clinical trials going on now looking at PD-1-, PD-L1-refractory patients in bladder cancer, and I think we are going to make some progress building off of this monotherapy immunotherapy baseline for many of these patients. So, therein lies the hope.

Transcript Edited for Clarity