Ulka Vaishampayan, MD: Who is the most appropriate patient for treatment with ipilimumab and nivolumab? Now that we have had FDA approval of this combination for some time, can you discuss the data as well as the appropriateness, or the patient selection, for this therapy? Rana?

Rana R. McKay, MD: We’re all familiar with CheckMate 214. It was a large, randomized phase III trial where patients were randomized to the combination of nivolumab and ipilimumab versus sunitinib in the frontline space. The primary end point was to look at outcomes in patients who had intermediate- and poor-risk disease. Recently presented at GU ASCO [Genitourinary Cancers Symposium] by Dr Nizar Tannir was the updated long-term follow-up with a minimum of 42 months, which is the longest time follow-up of outcomes from any of the frontline trials. The initial data were presented with a follow-up time of around 17.5 months. There was also a 30-month follow-up, and now we see the 42-month follow-up where we continue to see a statistically significant improvement in overall survival in the intermediate- and poor-risk patients. We see a survival of 47 months compared with 26.6 months. The hazard ratio holds steady at 0.66, with a 30-month hazard ratio also at 0.66.

It’s exciting to see that with longer-term follow-up, the benefit of nivolumab-ipilimumab is persistent. Additionally, we continue to see a tail on the curve of people who remain on treatment or are maybe off treatment but haven’t started their subsequent second-line therapy and are reaping the benefits of the combination regimen. We’re beginning to see these long, durable responses. We’re always leery of the word cure, but we’ve all seen patients in our clinic who are many years out and are either still on therapy or are off therapy—not on second-line therapy—and are doing well.

Ulka Vaishampayan, MD: Yeah, I agree. In the oncology world, where even a median improvement of 3 months is something that we occasionally get excited about, a median survival improvement of 21 months is pretty impressive. How durable are these responses with ipilimumab-nivolumab? Matt, can you see only in the responders?

Matthew T. Campbell, MD, MS: That’s a great question. With the data that we have so far from this CheckMate 214 study, around 85% of patients with a complete response will maintain response. If you look at all responders, they showed that at 2 years, 3 years, and then 4 years, around 66% of patients who initially responded were maintaining response. That’s a good fraction of patients. In terms of predicting patients who would have a durable PR [partial response], that’s a bit tricky, though there are some suggestions that patients who are getting below the threshold of 60%, 70%, or 80% response are responding in a similar fashion are the patients in a complete response.

There have also been several posters and abstracts that have suggested that they may be a special subgroup, kind of like in multiple myeloma, where they have very good partial response. In my own clinical practice, I particularly worry about relapse in the brain. There are patients for whom that is the site of relapse, so I make sure my patients are doing well and keep a close eye on their brain, at least annually.

Ulka Vaishampayan, MD: Does anybody else have comments on the response, and predicting for a durable remission?

Tian Zhang, MD: I think we all have patients like this in our clinics—patients who are doing very well, with a very deep partial response or a complete response. The critical clinical question to address for these patients is, when should we or could we hold therapy, understanding that the adverse effects from immunotherapies can really occur at any time? And so is there a point when we should discontinue treatment? We’ll talk about that in a bit.

Transcript Edited for Clarity