ESMO 2020 | CheckMate 9ER trial: nivo + cab vs sun 1L in advanced RCC

Hello, my name is Tom Powles. I’m a medical oncologist from London. I’ve been asked to talk about the 9ER study, which is a 650 patient trial in first-line metastatic clear cell renal cancer, comparing nivolumab and cabozantinib at 40 milligrams with sunitinib.

It’s very similar to the design of other studies in the frontline setting, which have used sunitinib as a control arm. The trial was positive for PFS, which was the primary endpoint, with a really impressive hazard ratio of 0.51. It went on to show overall survival, which was significant at 0.60. It also showed really impressive response data in the mid 50%. The overall efficacy data, as it stands, is very much in line with what we’ve seen for axitinib and pembrolizumab.

Remember the axi-pembro data started with a hazard ratio for survival of 0.53, and more recently the more robust analysis with longer follow-up. It’s important to remember that the cabo-nivo does have a longer follow up, so it’s in a similar ballpark to axi-pembro, and that more recent data with axi-pembro is 0.68. Overall, I can see more similarities than differences from an efficacy perspective. I think that it’s clear that the Veg-F TKI immune checkpoint inhibitor combinations, the two positive ones, because remember axitinib and avelumab, bevacizumab and atezolizumab have not yet achieved that survival hurdle, which I think is required. So axi-pembro and cabo-nivo, from an efficacy perspective, look to be really good at getting in control of early disease, generating an impressive survival advantage. A couple of provocative issues in the cabo-nivo data.

Number one, a lot of patients dose reducing from 40 to 20 milligrams. And on top of that, although 70 or over 70% of patients were getting a grade three or four toxicity, there did appear to be a quality of life advantage associated with cabo-nivo, which I think many people weren’t expecting because cabo and sunitinib probably have similar toxicity profiles. And then, of course, adding nivo to that should push things down perhaps a little bit, but that wasn’t the case; it was better. Whether or not that’s related to the lower dose of the cabozantinib, we don’t know. Access to subsequent therapies was relevant at 47% of patients getting access to subsequent therapy. It’s not high, it’s modest. As the trial progresses I’m sure more patients will get access to subsequent therapies. So let’s keep an eye on that. Overall, I think the best way of summarizing this data is to say the efficacy signal is impressive.

It’s as impressive in my opinion is axi-pembro. There are subtle differences in the trials and therefore direct comparisons aren’t actually that helpful. But actually when you look and compare it with a combination of drugs like ipilimumab and nivolumab, I think both axi-pembro and cabo-nivo are probably slightly better at getting overall earlier control of disease. I think in the favorable risk patients, both cabo-nivo and axi-pembro have a response and a progression-free advantage and, in the fullness of time, may achieve that overall survival signal as well. So my summary of the data, as it currently stands, is this is another option for patients with frontline metastatic clear cell renal cancer. I think that the data supports that. I think the tolerability profile is acceptable with impressive quality of life data and I’m looking forward to using the combination in the future.