Medicine Matters oncology

Patients start with nivolumab monotherapy. And after 16 week, based on the tumor assessment at that time point, we decide whether they need more intense therapy or not. For those who respond, they go on with nivo maintenance. And those who do not respond, these patients receive two to four cycles nivolumab plus ipilimumab, in order to get them into remission.

So this refers to those patients who are in stable disease, or with progressive disease at that time point. It was the aim of the study to reduce toxicity, we see grade 3-4 events in 46% of patients who start with nivo/ipi compared to 19% with nivo alone. So that was the aim of the trial when we designed it. However, we had an efficacy endpoint, which was objective response rate.

And the study was power to demonstrate an increase over the 25% we expected for nivo monotherapy. And the numbers were calculated on an increase to 40%. If you use nivo/ipi, have in the intermediate and poor risk patients with renal cell carcinoma, an objective response rate of about 42%. And our aim was to show that it's around 40%.

Finally, in the first line cohort, the objective response rate is 37%. So a little bit lower with what we see with nivo/ipi up front. But the data is not quite mature yet, because the primary endpoint was analyzed now after 30 weeks, and there may be some late responses.

So we will have another data cut, and see how the objective response rate, with our approach, is then. The safety results look compare favorably with nivo/ipi combination therapy. So we had a 32% grade 3-4 event. So it's just in between nivo mono and the combination.

And the discontinuation rate was around 14%, compared to 22% with nivo/ipi upfront. So it looks very well, I would say. There is a lot of more data now compared to the time when we designed the study, and what we see is that patients who have an adverse event with nivo/ipi have to discontinue treatment for that reason. They don't do worse than the overall cohort.

So the immune-related adverse events, which are most of these grade 3-4 events, they indicate that these patients respond also well to therapy. So I don't know whether this tailored approach will be used in many patients in the future. We need longer follow up, first of all.

And based on the data we have now, with longer follow up for the combination therapy, I think this will be something for selected patients, where you are afraid to use combination, which induces a strong immune response. Maybe for frail patients, we will see this has to be, the time will show.