Renal cell carcinoma (RCC), a type of kidney cancer, has been the focus of extensive research in recent years. The recent advancements in the treatment of renal cell carcinoma have provided new hope for patients with this challenging disease. As research continues, it is crucial to individualize treatment strategies based on patient risk profiles and explore novel approaches to address the specific needs of different RCC subtypes. Further research and clinical trials will undoubtedly continue to refine and expand our understanding of these groundbreaking therapies, with the ultimate goal of enhancing the quality of life and survival rates for individuals battling RCC.
Q1: Thank you, Professor Schmidinger. In this Proffered Paper session, the results of LITESPARK-003 and LITESPARK-005 were presnented.How do you comment these two studies?How do you think of the application prospects of HIF-2α inhibitors for aRCC patients?
A: So, I think this was a very interesting session for patients with renal cell carcinoma.
Tony Turiri presented the data from the Light’s Park 003 trial. This was a combination of Cabo Santini and Belzutifan, given in two different patient cohorts. One cohort was patients who had been treatment naive, and the other cohort were pre -treated patients.
So, in the cohort one, in the treatment naive patients, response rates went up to 70%. And I think this is really very, it was a very long duration of response of almost 29 months. And in cohort two, the response rates were also very high, and it was an even better duration of response of 30 months.
I think it’s a very promising combination. This is just a phase two trial for now. We will need to see where is the best place for this combination. Is it in first line? Is it maybe in the context of a triplet with immunotherapy?
Is it in the context of just two targeted agents who will see that? But definitely the data were very encouraging. respect to the Leitzbach 005 trial, Belsutifan versus Erolimus in patients who had failed prior treatments.
Here, of course, you may argue, well, Cabo Santini should have been a more realistic comparator here, but we need to acknowledge that 80% of the patients who are no longer in a second line setting, they were in a third or beyond third line setting.
So these were heavily pretreated patients, and Belsutifan clearly outperformed Erolimus in terms of the primary endpoint progression for survival and also in terms of response rates. Belsutifan is hopefully, and I’m pretty sure about it, going to be approved, and this is an agent that we really need.
You were asking what is my general opinion impression about Belsutifan in the context of kidney cancer. And I think it’s an agent that is interesting for multiple reasons. First, because of the mode of action.
Second, because of its single agent activity. Third, because of its excellent tolerance. Fourth, because it’s combinable with other targeted agents and also with immunotherapy. And we are waiting to see the data from the Leitzbach 011 trial, a randomized phase three trial on Pembrolizumab and Lenvatini plus Belsutifan versus Cabosanti in the second line trial.
Q2: The second question is Dr. Sheng Xinan also presented the results of the RENOTORCH study. How do you comment the RENOTORCH study based on the phase 3 studies of first-line immunotherapy that have been reported so far?
A: So this trial investigated the combination of Acetineep, very narrow TKI, in combination with Tori Palimab, PD1 inhibitor. The design has been very similar to the keynote 426 trial that was conducted in the US and the rest of the world in Europe.
And I think it’s very important to know that the difference here was that in the RENOTORCH trial there were no patients with favorable risk, just intermediate and poor risk patients. The comparator arm in that trial was Sunitineep and the combination of Tori Palimab and Acetineep clearly outperformed Sunitineep in the first line setting of intermediate and poor risk patients.
And I think the trial was very important in that context that this is the best way to bring these combination to the Asian market where Pembroke Pembrolizumab is not approved. Pembrolizumab Acetinib is a standard of care in the first line setting of kidney cancer, but it’s not available everywhere, and therefore it’s very important to have this positive trial, this positive renal torch trial because it would change the treatment landscape in Asia.
According to the topic of this session, management of EMDC, for variable risk patients in. So we know that the most of current studies show that the main benefits of combined immunotraplic and intermediate or poor risk patients, what do you think of the treatment strategy of EMDC for variable risk?
So from my point of view, I’m the see favorable risk patients most of the time should also be treated with an IOTKI combination. The reason being that even if we don’t see an overall survival advantage for the moment when compared to Sunitinib, what we have seen however is a significant improvement of progression free survival response rates and also complete response rates.
And maybe it’s because of these complete response rates as a main factor that drives my decision also in the favorable risk patients to consider IOTKI as the best treatment option. But of course there is patients who are also fine off just with observation or every kidney cancer patient with metastatic disease needs a treatment right away.
And also there is certainly a good number of patients in whom a TKI monotherapy might be appropriate. But it should be in general be made available also for favorable risk patient, the IOTKI combination.
And then it should be discussed on a patient by patient basis whether this patient needs the combo or just observation or a TKI.
Q3: Thank you. The last question. There are also some non-clear cell renal cell carcinomas in clinical practice, which is lack of therapeutic targets. Could you introduce the progress in the treatment of nccRCC?
A: So in non -clear cell RCC we have also seen big advances in fact in the last few years. At ASCO for example was the presentation of the keynote B61 trial that was a trial that conducted by Lawrence Albijes, good friend of mine.
And in this trial Lenvateneb was combined with Pembrolyzumap. Lenvateneb is a VGF and FGF inhibitor was combined with a PD1 inhibitor. And this trial showed really very nice results with a very high response rate, also in patient of non -cliosal histology response rate, about 40%, even in the setting of chromophobar, CC, which is believed to be less immune, less susceptible to immunotherapy.
Another combination that I believe is quite important is combination of immunotherapy, PD1 inhibitor with kabosantinib, metaxl and VGF inhibitor. Also, this combination has shown a response rate above 40% in the non -cliosal setting.
But certainly this field is the one where we need even more research. It’s a very difficult research because the group of patients with non -cliosal is very heterogeneous.
