ESMO 2025 Kidney Cancer Highlights
We rounded up a few research highlights from the 2025 Congress of the European Society for Medical Oncology (ESMO), held recently in Berlin, Germany.
Is a triplet of drugs a superior first-line treatment strategy?
Among four different combinations of first-line triplet therapy for advanced kidney cancer, all including pembrolizumab, one showed promising efficacy compared with the reference study arm in which patients were given pembrolizumab + lenvatinib.
KEYMAKER-U03 sub study 03A is a smaller investigation within the larger KEYMAKER trial. The sub stdy compared triplet first-line combination treatments in 353 people with advanced clear cell renal cell carcinoma (ccRCC) against the reference arm, followed up between 16 and 39 months. The combinations were:
- favezelimab + pembrolizumab + lenvatinib
- vibostolimab + pembrolizumab + belzutifan (this arm was compared to pembrolizumab+belzutifan)
- quavonlimab/pembrolizumab + lenvatinib
- belzutifan + pembrolizumab + lenvatinib
Response rates and progression-free survival were not immediately evidently superior to the reference arm but discussant Dr. Lisa Pickering said durable response rates over a longer period of time remain to be seen. The belzutifan + pembrolizumab + lenvatinib group was the only triplet that performed similarly – though not better than – the reference arm, with overall response rates of 77.5% compared with 80.6%, respectively, and progression-free survival that exceeded 30 months. The results from the phase 3 LITESPARK012 trial could reveal more about how belzutifan + pembrolizumab + lenvatinib performs long-term.
Serious side effects are also a major consideration, especially as treatment options move into drug trios, and over half the patients in all the treatment groups reported serious side effects consistent with the known side effects from these drugs. [ESMO 2025, Abstract LBA96]
Lenvatinib + everolimus had better cancer control than cabozantinib alone
A phase 2 trial of people whose kidney cancer progressed after treatment with immunotherapy showed that a combination of lenvatinib plus everolimus was superior to treatment with cabozantinib alone, although there was no overall survival benefit.
The trial included 86 people with metastatic clear cell RCC – 40 given lenvatinib plus everolimus and 46 given cabozantinib – followed for an average of 20 months.
During this time, 60 people saw their cancer start to grow again. Progression-free survival was 16 months in the lenvatinib plus everolimus group, longer than 10 months in the cabozantinib group, but overall survival data was not ready at the time this study was presented.
“Is [the results] positive enough? I think that depends on you and your patient,” said Lisa Pickering.
“But I would say that we can and should consider using lenvatinib plus everolumis particularly in patients for whom the priority is response and for whom the higher toxicity rate is acceptable.”
Unmet needs in kidney cancer: The IKCC global patient survey 2024*
Kidney cancer rates are rising, increasing pressure on patients, families, and healthcare systems. Since 2018, the International Kidney Cancer Coalition (IKCC) and its network have tracked global trends in diagnosis, management, and patient burden through a biennial global patient survey. The survey identifies patient experiences, unmet needs, and differences by country to inform recommendations for the diagnosis, management, care and treatment of kidney cancer patients globally. Some key findings from the survey were presented in a poster at ESMO 2025. The survey was created for kidney cancer patients and caregivers by a steering committee from the IKCC network, in collaboration with kidney cancer patient advocates, medical experts, and the Picker Institute. It was tested to make sure it was reasonable through interviews with patients and caregivers. It was translated into 16 languages.
Between September and November 2024, a total of 2,677 individuals took part (2,049 patients and 628 carers) from 46 countries. Of these, half were male, 8 in 10 were aged 46–80 years, and two thirds had clear cell kidney cancer. One in 5 patients were stage 4 at diagnosis, with half of the patients being diagnosed within the last four years.
Key findings:
- Just over half of people who answered the survey (55%) said they were involved in making decisions about their treatment as much as they wanted, but this differed from country to country.
- Most patients (79%) taking targeted medicines continued with their treatment as planned. The main reasons people stopped or reduced their medication were side effects, feeling unwell, problems with daily life, or running out of tablets. The survey suggests that people are more likely to stick to their treatment if they are more involved in decisions and have good information about their health.
- The vast majority (85%) said kidney cancer had affected their emotions, but only a third of those who felt anxious about their illness talked to their doctor or nurse about it.
- Nearly two out of three people (62%) said they were never asked to join a clinical trial, but of those who were invited, two out of three (63%) took part. Of those who joined a clinical trial, most (77%) were happy with their experience.
IKCC is a global support and advocacy network for organizations serving the kidney cancer community. The IKCC global patient survey is the only worldwide survey for people affected by kidney cancer, and 2024 saw the highest number of participants ever. The survey found that there are still big differences in how much patients feel included in making decisions about their treatment, depending on their country. Most patients stick to their treatment plans, but results could be better if patients had more information and were more involved in decision-making. About one in five people who took part in clinical trials were not happy with their experience. Many people said their mental health was affected by kidney cancer, but these feelings were rarely talked about with their doctors. Experiences vary a lot from country to country, showing there is more to learn and more ways for patient groups and healthcare professionals to work together. [ESMO 2025, Abstract 2631P]
*Excerpted from the IKCC’s summary of kidney cancer ESMO highlights.