What I presented at this meeting was the CHECKMATE-214 study which is a first line study in metastatic kidney cancer looking at the combination of nivolumab and ipilimumab compared with sunitinib. The rationale behind it was that this combination has been tested in several tumour types, active in melanoma as an example, and in renal cancer we did a phase I which was quite encouraging with good response rate, good survival. So we went to this large phase III, more than 1,000 patients where nivo and ipi is given together for four doses, nivo 3mg/kg, ipi 1mg/kg, every four doses and then maintenance therapy with nivolumab compared with sunitinib as a control arm. More than 1,000 patients, the primary endpoint was in intermediate and poor risk patients, so classification by what we call IMDC in renal cancer.
Most of the patients were poor and intermediate risk patients although we had also a group of good risk patients, 250 patients here. All patients had tumour available for PD-L1 testing which is one of the exploratory endpoints we did. So that’s the patient population and the study design here.
When we look at the data now, first of all we had three co-primary endpoints in intermediate and poor risk patients: response rate, PFS and survival. All the three are improved; OS is improved significantly, hazard ratio is 0.63 which means a 37% reduction in the risk of death. 26 months for sunitinib, not yet reached for nivo/ipi. The second objective, response rate, is much higher with nivo/ipi, 42%. Moreover 9% of patients have a complete remission and probably are cured. Durable responses are seen with this regimen. The third endpoint, PFS, improvement by more than three months which is not statistically significant here but p-value is 0.03 which is still very good here. So overall very good data in poor and intermediate risk patients.
The second message: it’s manageable. The safety profile was as expected and the grade 3/4 toxicities are less than we have with sunitinib. As a consequence of that quality of life was better in the study with nivo/ipi than it is with sunitinib which was anticipated but good to confirm here.
We had two important exploratory endpoints – one was to look at the good risk patients, the patients which were not intermediate and poor risk. Surprisingly in this group of patients sunitinib seems to be better, at least in terms of response rate and PFS here. So we have to wait for survival but that might not be the best group of patients to treat with nivo/ipi. The second exploratory endpoint which is of interest here is that patients who do express PD-L1, which represent overall 25% in our study here, those patients do really good – PFS and response rate are much higher; as well sunitinib has a lower efficacy here. Complete remission in this group of PD-L1 positive is 16% of patients who have complete remission. So certainly the global conclusion of this one that’s going to become the new standard of care in patients with metastatic kidney cancer, certainly in patients in the intermediate and poor risk group, maybe not in good risk patients. Whether we should have to look at PD-L1 expression is something we’ll have to confirm later on but that’s going to become very soon the new standard of care.
Whilst this trial was looking at sunitinib as a single agent, are there any considerations for comparison to the recent CABOSUN trials?
The CABOSUN was also updated at this meeting and certainly cabozantinib is one of the drugs we could use in the intermediate and poor risk patients. My interpretation of the data is that nivo/ipi is probably better than it is with cabo, although we don’t have a head to head comparison. My personal view is that as CABO is superior to sunitinib one thing I would probably like to do if possible is to use cabo in good risk patients and maybe some specific poor and intermediate risk patients like bone mets patients here and I would keep nivo/ipi for the majority of the other patients. But it’s going to change a lot because I think in the near future only nivo/ipi and cabo will be used in first line. So it’s going to change a lot.