Alicia Morgans: Hi. I’m thrilled to have here with me today Dr. Cora Sternberg, who’s a medical oncologist and the Clinical Director of the Englander Institute for Precision Medicine at Weill Cornell. Thank you so much for being here.

Cora Sternberg: It’s a pleasure.

Alicia Morgans: Wonderful. So I wanted to talk with you about some data in the SAUL study, which you shared with us at EAU, and which has been recently published in European Urology. Can you tell us a little bit about it?

Cora Sternberg: Sure. The SAUL study is a really interesting study. It’s a real-world study with patients from over 30 countries, and over 1000 patients, that were placed on a drug called atezolizumab. This is immunotherapy. It’s a checkpoint inhibitor. It’s a humanized monoclonal antibody against PD-L1, and it blocks the binding of PD-L1 and PD-1, and it blocks binding with something called D7. And what it does is it makes patients’ own T-cells work better.

It’s been approved in bladder cancer for patients who have already failed cisplatin chemotherapy, and it’s been approved also for those patients who are ineligible for cisplatin chemotherapy, particularly if they have their PD-L1 status that is positive, meaning more than five percent immunocompetent cells that are PD-L1 staining. However, in the United States, it’s approved for all patients who are ineligible for cisplatin.

What happened was that after the drug was approved in the United States, it takes some time to get it approved in the rest of the world, and all of these studies are done in patients who are highly selected. All these registration studies. Patients are different than patients in the real world, so what we did was we got together and decided who was not allowed into the study, and we allowed patients into the study who had poor creatinine, patients who were on dialysis, patients who were on steroids, patients who had immunological defects, patients with poor performance status, patients with brain tumors, even patients with HIV. And also patients with other histologies than transitional cell, so it was really the real world in population done in many countries all over the world. It wasn’t necessarily the investigators who took part in the registration studies. So it’s a broad-based experience.

And what we found was that it was possible to give immunotherapy to this group of patients. 35% of the patients were in these categories that I just mentioned. 98% of them had had prior cisplatin chemotherapy as well, and what we found was that the median overall survival for the whole group was 8.7 months, which was really what was found in the registration study called IMvigor211, the same median overall survival.

So patients, this means a lot because a lot of patients have been left out of the possibility of receiving an immune checkpoint inhibitor. I’ve worked with bladder cancer for quite a long time, and if patients have metastatic disease and they fail cisplatin-based chemotherapy, such as gem platinum or MVAC, there really were not any good choices for any of these patients, and I now have patients who have been on immunotherapy that have complete responses that are long-lasting, even after they’ve stopped the immunotherapy. To not be able to be on treatment because you have been on low dose steroids, or because you have rheumatoid arthritis, or psoriasis, or colitis, or any of these reasons was really leaving out quite a lot of people. So we now know that we can pretty safely… Obviously, we have to monitor the patients… Give this drug even to patients with this kind of problems, which is, I think, quite a big deal, and it’s quite practice changing.

We have also looked at the PD-L1 status of the patients and it’s true that the patients who have PD-L1, 2 or 3, which means more than five percent of their cells stain as immunocompetent cells for PD-L1, they do do better, have better overall survival than the ones who are PD-L1, zero or one.

We’ve also just looked at the patient’s age and grouped them into age groups over 65, over 70, over 75, and over 80. It’s true that the patients over 80 received fewer doses of treatment for a variety of reasons, but they actually all did very well. All of the patients in all of these age groups, and there were not really increased toxicity in any one of the age groups. So we feel pretty confident that elderly patients can receive this therapy, so it’s really quite news. I think it’s good news and practice changing.

Alicia Morgans: I completely agree, and I think that the benefit of these real-world studies is exactly as you mentioned, that we are able to capture all of these patients that we see in our clinical practice every single day, but who are excluded for safety reasons in most cases from clinical trials. And just to reiterate, patients in this trial could’ve had autoimmune disorders like rheumatoid arthritis, or psoriasis, or any of the other things that they may need to be on a low dose of prednisone for or perhaps other medications, and we did not in this trial at least see that there were high levels of colitis or skin problems or pneumonitis or other complications that could require hospitalization. These patients actually tolerated the treatment well, and so that’s something that we should recognize in our practices moving forward.

Cora Sternberg: The side effects were very similar to what has been seen in all the registration studies. Fatigue and asthenia in a certain percentage of patients, but not a higher percentage. And also those patients that have not been in studies, the non-transitional cell, the bellinis and the other histology, those patients also did well in this study. So that was another interesting thing to know, that we can treat these patients with immunotherapy.

Alicia Morgans: Absolutely, and I think particularly in patients who have things like small cell, squamous, these other histologies that we sometimes see, and we’ve already tried treating them with cisplatin, we need actions. And so at least we know that it’s safe. We don’t necessarily have … Were the responses for these patients the same?

Cora Sternberg: The responses and the overall survival was the same. The patient group who did the worst were the patients who were performance status two. They did a little bit worse, worse than the patients with immune disease or renal failure or even dialysis. The patients with performance status two. But as we well know, sometimes when patients are put in studies and performance status two was a judgment, maybe they were a performance status three, maybe these really were sicker patients, so I can’t really say. But they did a little bit worse in general in the whole study.

Alicia Morgans: And that makes sense. These are sicker patients, and they’re not going to be able to live as long and get as much treatment potentially. So this is, as you said, really important. Supports our understanding of the use of atezolizumab in real clinical practice, and is really practice-changing in that way. So, if you had one message, one take-home message from the SAUL study that you really wanted to communicate to clinicians out there, taking care of patients with urothelial cancer, or a bladder or upper track cancer that’s a different histology, what would your message be?

Cora Sternberg: Patients who have failed cisplatin based chemotherapy or carboplatin based chemotherapy can be treated safely with immunotherapy. I don’t know if this carries over to all immunotherapy, but it probably does, but this is the only large study like this. And I think that if you’re going to treat patients with immune disease or with colitis or other things, you should work together in a multidisciplinary way with a gastroenterologist, with their dermatologist if they have psoriasis, or whatever so that you make sure you don’t have more toxicities. But we did not see more toxicities, and these patients should be allowed to enter into not necessarily into trials, but to be treated with these therapies.

Alicia Morgans: Absolutely. And it also emphasizes, too, and I’d like to emphasize the benefit of these real-world trials that help inform some areas of gray data, where we really have a clinical need, and I appreciate that you’ve contributed to meet that need. So thank you so much for your time today.

Cora Sternberg: Thank you. It was a pleasure.