News

Source: International Kidney Cancer Coalition (IKCC)

This year’s American Society of Clinical Oncology Genitourinary Cancers (ASCO GU) Symposium was held from 13-15 February 2025, in San Francisco, California, USA. The presentations are available to view on the ASCO website. Some affiliates of the International Kidney Cancer Coalition (IKCC) went to the meeting to keep up to date with the care and treatment of patients with kidney cancer. A brief ‘Take home messages’ section is followed by more in-depth review of selected abstracts.

Please note: The following summary was prepared for the benefit of patient advocates and patient organisations around the world who focus on kidney cancer. While this summary has been medically reviewed, the information contained herein is based upon public data shared at this meeting and is not intended to be exhaustive or act as medical advice. Patients should speak to their doctor about their own care and treatment.

Take home messages

• Abstract 467 discussed the burden of metastatic kidney cancer for patients. People living with metastatic kidney cancer are physically and mentally consumed with cancer and disease management. Metastatic kidney cancer disrupts basic daily activities, such as eating, sleeping, and socialising. Patients must routinely engage with the healthcare system, managing appointments with multiple healthcare providers. Importance: Nearly all patients think about their cancer daily. More research is needed to improve care and reduce the burden of metastatic kidney cancer for patients.

• Abstract 459 reported no differences in the patient reported outcomes (PROs) between the patients who were treated with the combination of tivozanib plus nivolumab and those treated with tivozanib alone. Patient reported outcomes suggested that quality of life was maintained from the start to the end of treatment. Importance: Although the study did not show any clinical benefit from adding nivolumab to tivozanib in patients who had already been treated with immunotherapy, the addition of nivolumab did not affect the quality of life of these patients and quality of life was maintained from the start to the end of treatment.

• Abstract 437 reported biomarker results from the CheckMate 214 study comparing the combination of nivolumab plus ipilimumab with sunitinib. Increased levels of kidney injury molecule-1 (KIM-1) in the blood of advanced kidney cancer patients before treatment were linked with worse clinical outcomes. A reduction in KIM-1 levels in the blood 3 weeks after the first cycle of immunotherapy was linked with improved survival. Importance: Blood KIM-1 levels may be a useful biomarker for monitoring advanced kidney cancer patients on immunotherapy.

• In abstract 444, durvalumab plus savolitinib continues to show encouraging outcomes in patients with papillary kidney cancer. Levels of circulating tumour DNA (ctDNA) in the blood of papillary kidney cancer patients can be linked with shorter survival time, and stable or progressive disease. Importance: Monitoring circulating tumour DNA levels in the blood during treatment holds promise as a potential biomarker for outcomes and prognosis for patients with advanced papillary kidney cancer.

• Abstract 441 reported results from a phase 1 study with a new HIF-2α inhibitor, called casdatifan. Casdatifan was well tolerated and showed promising anti-cancer effectiveness in previously treated patients with advanced clear cell kidney cancer. Importance: Further clinical trials are needed to prove the anti-cancer effectiveness of casdatifan, two of which are ongoing to test casdatifan in combination with VEGFR TKI targeted therapy and immunotherapy.

• In abstract 438, new information from the COSMIC-313 study was presented showing that treatment of previously untreated advanced kidney cancer patients with a triple combination of cabozantinib, nivolumab and ipilimumab continued to show a progression free survival benefit compared to nivolumab plus ipilimumab. However, overall survival time was similar for both the triple combination and nivolumab plus ipilimumab. Patients with high levels of a white blood cell, called M2 macrophage, had improved overall survival with the triple combination. Importance: Further analysis of biomarkers in kidney cancer tumours is ongoing to predict which patients respond to this triple combination.

• In abstract 439, five and a half years follow up results from the cabozantinib plus nivolumab study showed that patients with previously untreated advanced kidney cancer continue to benefit and respond to treatment, regardless of the severity of their disease. Importance: This study shows that the survival benefits from treatment with the cabozantinib plus nivolumab combination are long lasting and support this combination as a standard of care for previously untreated patients with advanced kidney cancer.

• In abstract 440, the combination of lenvatinib plus belzutifan for advanced kidney cancer had long lasting anti-tumour activity and side effects were in line with those reported from previous studies.Importance: More work is needed to support the use of this combination in routine clinical practice, and a phase 3 clinical study is currently ongoing to look at the lenvatinib plus belzutifan combination in patients with advanced kidney cancer who have previously been treated with immunotherapy.

• Abstract 533 presented the results from the CABRAMET study. This study presented some promising information regarding the management of kidney cancer brain metastases. Importance: This study goes a long way to address an unmet need in kidney cancer patients with brain metastases.

• Abstract 555 showed that neoadjuvant treatment (before surgery) of patients with locally advanced kidney cancer with a combination of lenvatinib plus pembrolizumab was effective at controlling the growth of, and in some cases, shrinking the tumour before surgery. Importance: Long term outcomes are needed to determine the exact role of anti-cancer treatment before and after surgery (perioperative treatment) in the management of locally advanced kidney cancer.

• In abstract 543, the addition of the probiotic bacterium, CBM588, to the cabozantinib plus nivolumab combination continues to show promising effectiveness in patients with metastatic kidney cancer, with improved response to treatment and survival. Side effects of CBM588 are in line with those reported from previous studies. Importance: These results support larger studies in more patients with CBM588. Further work is ongoing to try to find out how CBM588 improves clinical benefits.

Summaries

The burden of metastatic kidney cancer for patients and patient reported outcomes

Abstract 467

The burden of metastatic kidney cancer for patients

The use of combinations of anti-cancer medications and the sequencing if these treatments has significantly improved outcomes for patients with metastatic kidney cancer. This study looked at the burden of metastatic kidney cancer on patients and the interference of the cancer with daily life.

The Kidney Cancer Research Alliance (KCCure) developed a survey, which was administered to patients in September and October 2024 via their website, mailing lists and social media platforms.

1167 patients responded to the survey. Of these, 2 in every 5 patients had been treated with anti-cancer medication for metastatic kidney cancer, and 7 in 10 of the patients on anti-cancer medication had evidence of cancer. Nearly half of the patients were taking 7 or more medications per day. One-third of patients were concerned they were taking too many medications.

In the last year, almost half of the patients were hospitalised, and patients reported seeing on average more than 4 different types of doctors for their cancer care. In the last 90 days, more than a third of patients had visited the emergency room, 1 in 5 patients more than once. Nearly all patients had blood samples taken at least once and had at least one clinic visit. 1 in 5 patients had visited the clinic 5 or more times and nearly a third of patients had 5 or more visits to the pharmacy. Nearly a quarter of patients had been hospitalised. Of the patients who were hospitalised, half were hospitalised at least once, and 1 in 10 were hospitalised 5 or more times in the last year. Hospitalisations and visits to the emergency room resulted in poorer quality of life and greater distress for patients.

Most patients (9 in 10) think about their cancer every day, some for several hours a day. When asked how confident they feel about making plans, a third of patients said they feel completely confident making plans 6 months from now, while only 1 in 10 patients felt confident making plans for 2 years in advance. Patients with no evidence of disease were more likely to report excellent quality of life, compared to patients with evidence of disease, regardless of the treatment they were taking. Patients who stopped treatment but still had evidence of disease reported poor quality of life.

The most common everyday activities always or often affected by cancer were reported to be eating a meal, sleeping, socialising with friends, shopping for food, travelling, buying cloths, and attending an event.

People living with metastatic kidney cancer are physically and mentally consumed with cancer and disease management. Metastatic kidney cancer disrupts basic daily activities, such as eating, sleeping, and socialising. Patients must routinely engage with the healthcare system, managing appointments with multiple healthcare providers. Nearly all patients think about their cancer daily. More research is needed to improve care and reduce the burden of metastatic kidney cancer for patients.

abstract 459

Patient-reported outcomes for kidney cancer patients on tivozanib plus nivolumab compared to tivozanib alone following immunotherapy

In the TiNivo-2 study kidney cancer patients were treated with a combination of tivozanib plus nivolumab after their cancer had stopped responding to immunotherapy. The TiNivo-2 study did not show benefit for the patients of adding nivolumab to tivozanib compared to tivozanib alone in patients who had already been treated with immunotherapy. However, there was some benefit of using tivozanib as a second- or third-line treatment after immunotherapy, with longer survival times and fewer treatment-related side effects for tivozanib. In this presentation, quality of life information was reported.

Patients completed quality of life questionnaires at the start of the study (before treatment), at the start of each cycle of treatment, and at the end of treatment. The number and percentage of patients having improved, stable, or worse quality of life were recorded.

Patients were followed up for one year. The average duration of treatment was a little over 6 months for tivozanib plus nivolumab and 7 months for tivozanib alone.

There were no differences in the patient reported outcomes between the patients who were treated with the combination and those treated with tivozanib alone. Patient reported outcomes suggested that quality of life was maintained from the start of the study to the end of treatment.

Biomarkers for kidney cancer

A biomarker is something that can be measured in the blood, urine or body tissue to indicate a biological state, disease or condition. In cancer, a biomarker could be a protein circulating in the blood, a protein made in the tumour cell, or a change in the genes in the tumour cell (gene mutation). Biomarkers have multiple functions; they could help diagnose the disease, predict its response to treatment, and could give information about the outcomes of the disease for a patient.

Currently, the prediction of outcomes for patients with kidney cancer is based on the stage, grade, subtype, and overall health of the patient. Reliable biomarkers for predicting the response of individual patients to kidney cancer treatments and the outcomes of the disease are an unmet need. The identification of a biomarker could help doctors personalise treatment to individual patients to maximise benefits and improve outcomes.

Two presentations at ASCO GU this year looked at biomarkers for kidney cancer: kidney injury molecule-1 (KIM-1) as a predictive biomarker for advanced kidney cancer and circulating tumour DNA for the outcomes and prognosis of advanced kidney cancer patients.

Abstract 437

Evaluation of kidney injury molecule-1 (KIM-1) as a predictive biomarker in advanced kidney cancer

The immunotherapy combination of nivolumab plus ipilimumab was the first combination therapy to be approved for previously untreated patients with advanced or metastatic kidney cancer. The combination of nivolumab and ipilimumab is an established first line standard of care for patients with advanced kidney cancer.

Previous studies have shown that high levels of a protein called kidney injury molecule-1 (KIM-1) in the blood are associated with worse prognosis. Low levels of KIM-1 in the blood are linked to benefit from immunotherapy.

In this study, KIM-1 levels in blood samples collected during the CheckMate 214 study, which compared the combination of nivolumab plus ipilimumab with sunitinib, were measured before the first dose of study medication (at baseline) and after one cycle of treatment. Researchers were looking to see if KIM-1 levels in the blood of these patients are linked to treatment outcomes.

The blood from 821 patients in the CheckMate 214 study was analysed for KIM-1 levels. For both treatment groups (nivolumab plus ipilimumab and sunitinib) higher baseline KIM-1 levels were linked to shorter overall survival time. This was not related to the severity of the disease, whether the patient had surgery, or the amount of cancer in the patient’s body. A reduction in the levels of KIM-1 from baseline to 3 weeks after the first dose of study medication was strongly linked with survival for patients treated with nivolumab plus ipilimumab, but not for patients treated with sunitinib.

In the CheckMate 214 study, increased levels of KIM-1 in the blood of advanced kidney cancer patients before treatment were linked with worse clinical outcomes. A reduction in the levels of KIM-1 in the blood just 3 weeks after a single cycle of nivolumab plus ipilimumab treatment was linked with improved survival of patients on this immunotherapy combination treatment. Blood KIM-1 levels may be a useful biomarker for monitoring advanced kidney cancer patients on immunotherapy.

Abstract 444

Circulating tumour DNA and survival data in patients with advanced papillary kidney cancer

The phase 2 CALYPSO study reported anti-cancer activity for the combination of durvalumab (an immunotherapy infusion called a PD-L1 inhibitor) and savolitinib (a targeted therapy tablet called a MET inhibitor) in patients with papillary kidney cancer.

A protein called MET (also called hepatocyte growth factor receptor) has been found to stimulate the growth and development of tumours. Savolitinib can block MET and has been shown to be effective in patients with papillary kidney cancer who have changes in the gene that makes the MET protein (MET-driven papillary kidney cancer). The final results from the study were presented, along with a new test for circulating tumour DNA (ctDNA).

Circulating tumour DNA (ctDNA) is found in the bloodstream and refers to DNA that comes from cancerous cells and tumours. Most DNA is inside a cell’s nucleus. As a tumour grows, cells die and are replaced by new ones. The dead cells get broken down and their contents, including DNA, are released into the bloodstream. The quantity of ctDNA varies among individuals and depends on the type of tumour, its location, and the stage of the cancer.

ctDNA can be used as a biomarker to help detect and diagnose a tumour, guide treatment, monitor treatment, and monitor outcomes of treatment.

After nearly 3 and half years follow up, nearly 6 in 10 patients with MET-driven papillary kidney cancer responded to treatment, and the time to when the treatment stopped working and the cancer started growing again was nearly a year and a half. Overall survival time was more than 2 years (27.4 months) in patients with MET-driven papillary kidney cancer.

Nearly two thirds of patients had tumour DNA in their blood at the start of the study. These patients had a shorter survival time than those without ctDNA (7.3 vs 36.4 months). Patients who responded to treatment with a complete or partial response had a reduction in ctDNA during treatment, while those with stable or progressive disease had an increase in ctDNA. When ctDNA disappeared from the blood during treatment, this was linked with improved survival.

Durvalumab plus savolitinib continues to show encouraging outcomes for patients with MET-driven papillary kidney cancer. ctDNA monitoring during treatment holds promise as a potential biomarker for outcomes and prognosis for these patients

New treatments for advanced kidney cancer

Abstract 441

A new HIF-2α inhibitor shows promising anti-tumour activity in kidney cancer

Treatments for people with metastatic kidney cancer have changed over the past decade, resulting in big improvements in patient outcomes and survival. However, for most patients, unfortunately their cancer eventually gets worse on current treatments.

Studies looking at the genes of people with kidney cancer have shown mutations in a gene called the von Hippel-Lindau (VHL) gene. This results in high levels of a protein called hypoxia-inducible factor, or HIF-2α in tumour cells. HIF-2α causes changes in the cancer cells resulting in the growth of the tumour. A new treatment, called a HIF-2α inhibitor, is a tablet that blocks the action of HIF-2α and tumour growth. A HIF-2α inhibitor called belzutifan is already available in some countries for the treatment of VHL associated kidney cancer and for heavily pretreated patients with advanced kidney cancer. The results of a phase 1 study with a new HIF-2α inhibitor called casdatifan were presented.

The patients in the study had clear cell kidney cancer and had previously been treated with immunotherapy and a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) targeted therapy, but not any HIF-2α inhibitors.

There were 68 patients in the study. Four patients were in the dose escalation part of the study to look for the best dose of casdatifan to give to patients. The average number of previous anti-cancer medications was three. Patients were followed up in the study for around a year.

About a third of patients with favourable disease responded to treatment, while 1 in 5 patients with intermediate or poor risk disease responded to treatment.

Four in 10 patients reported severe or life-threatening side effects with the higher dose of casdatifan (50mg twice a day), and a third of patients reported severe or life-threatening side effects with the lower dose of casdatifan (50mg once a day). About a third of all patients had significant anaemia, regardless of the dose they took, and less than 1 in 10 patients reported low blood oxygen levels (significant hypoxia).

Casdatifan was well tolerated and showed promising anti-cancer effectiveness in patients with advanced clear cell kidney cancer who had already been treated with multiple anti-cancer medications. Further clinical trials are needed to show the anti-cancer effectiveness of casdatifan, and two clinical trials are planned: a phase 3 clinical trial of casdatifan in combination with a VEGFR TKI targeted therapy (cabozantinib) and casdatifan in combination with immunotherapy (volrustomig) in a separate study.

Combination treatments continue to show promise as first treatments

Advanced kidney cancer is often treated with a combination of immunotherapy medicines (nivolumab and ipilimumab) or immunotherapy (avelumab, pembrolizumab or nivolumab) plus a VEGFR TKI tablet (axitinib, lenvatinib, or cabozantinib). In some countries, these combinations are now considered as standard treatment for previously untreated patients with advanced kidney cancer. Other combinations are in development. Because long-term control of the cancer is an essential aim of treatment, updated results from clinical studies are important. Therefore, we will cover the long-term results of treatments that have previously been shown to be effective.

At ASCO GU this year, there were presentations of updated results from some ongoing studies. But crucially, none of these studies can help us with the critical question; which combination of treatments is best for an individual patient with advanced kidney cancer?

Overall survival for previously untreated patients with advanced kidney cancer on a triple combination of cabozantinib with nivolumab and ipilimumab

Cabozantinib is a VEGFR TKI targeted therapy that prevents cancer cells from multiplying by blocking abnormal proteins. It works by stopping the action of proteins called tyrosine kinases that are involved in the growth of tumours. Cabozantinib may improve the effectiveness of immunotherapy. COSMIC-313 is the first study to combine cabozantinib with two immunotherapy medicines, nivolumab and ipilimumab. This combination of three medicines is compared with a combination of ipilimumab, nivolumab and placebo for the treatment of people with intermediate- or high-risk advanced kidney cancer.

855 patients were assessed in this phase 3 study. Patients were randomly put in one of two groups to be treated with either nivolumab, ipilimumab plus cabozantinib or nivolumab, ipilimumab plus placebo. The study was double-blind, meaning both the doctor and the patient did not know which treatment they were on. All patients had clear cell kidney cancer that was of intermediate- or high-risk.

Early results from the clinical trial showed that adding cabozantinib to nivolumab plus ipilimumab significantly increased the time to when the treatment stopped working and the cancer started growing again (progression-free survival). Updated results were presented, including overall survival time.

Three quarters of the patients in the study had intermediate-risk cancer, and one quarter had poor-risk cancer. After a follow-up of three years and 9 months, the improvement of progression-free survival was maintained with the triple combination (16 and a half months for the triple combination compared to 11 months for ipilimumab plus nivolumab). Also, response to treatment was higher compared with ipilimumab plus nivolumab (46% versus 37% of patients), with fewer patients having progressive disease for the triple combination. However, there was no difference in overall survival time between the two treatment groups.

Severe and life-threatening side effects were reported by 81% of patients on the triple combination, and 62% on ipilimumab plus nivolumab. The most common severe or life-threatening side effect was changes in liver function.

An exploratory look for biomarkers in the tumour tissue of these patients showed that high levels of a white blood cell, called an M2 macrophage, was associated with improved overall survival in patients treated with the triple combination of cabozantinib, nivolumab and ipilimumab. An M2 macrophage is a type of white blood cell that surrounds and kills microorganisms or cancer cells, removes dead cells, and stimulates the action of other immune system cells. High M2 macrophage levels in the tumour were also associated with poor risk, high numbers of tumours at the start of the study and spread of the cancer to the internal organs.

First-line treatment with a triple combination of cabozantinib, nivolumab and ipilimumab continued to show a survival benefit for patients in terms of progression-free survival and response to treatment when compared to nivolumab plus ipilimumab. However, overall survival time was similar for both the triple combination and nivolumab plus ipilimumab. Patients who have high M2 macrophage levels in their tumours had improved overall survival with the triple combination of cabozantinib, nivolumab and ipilimumab. Further analysis of biomarkers and the immune cells in kidney cancer tumours is ongoing.

Five and a half years follow-up with cabozantinib plus nivolumab: does the benefit continue?

The phase 3 clinical trial, CheckMate-9ER, shows that cabozantinib (a VEGFR TKI tablet) used together with nivolumab (an immunotherapy infusion) is better than VEGFR TKI alone at shrinking the cancer, and improving survival in patients with advanced kidney cancer who had not previously taken any treatment.

Further follow up information was presented at the ASCO GU meeting this year. After more than five and a half years, the combination of cabozantinib plus nivolumab continues to improve survival, control the cancer, and shrink the cancer on scans compared with sunitinib (a VEGFR TKI tablet).

There were 323 patients in the nivolumab plus cabozantinib group, and 328 in the sunitinib group. The time to when the treatment stopped working and the cancer started growing again was nearly doubled with the combination treatment compared with sunitinib (16.4 months versus 8.3 months, respectively). Average overall survival time was more than 11 months longer with the cabozantinib plus nivolumab combination (46.5 months compared with 35.5 months for sunitinib). 4 in 10 patients survived for 5 years or more on cabozantinib plus nivolumab, while 3.5 in 10 patients survived 5 years or more on sunitinib. The number of patients who responded to treatment doubled with the combination (56%) compared with sunitinib (28%). Additionally, 13.6% of the patients on the combination treatment had a complete response to treatment and their cancer disappeared, compared with 4.6% for sunitinib. Also, the number of patients responding to the combination at 5 years was more than double that for sunitinib (22 % compared to 10 %).

Slightly more patients experience side-effects with the combination (97% versus 93%), and the side effects were more severe. This was like previous studies of this combination.

After more than 5 and a half years follow-up, patients continue to benefit from the cabozantinib plus nivolumab combination. Patients continue to respond to treatment, regardless of the severity of their disease. The cabozantinib plus nivolumab combination was also effective in patients who had spread of their cancer to areas of the body that are difficult to treat, such as bone, liver, and lung metastases. There were no new side effects reported. These results support nivolumab plus cabozantinib as a standard of care for previously untreated patients with advanced kidney cancer.

Combinations of pembrolizumab and targeted therapies for advanced clear cell kidney cancer

The phase 1/2 KEYMAKER-U03 study is looking at different combinations of immunotherapy and targeted therapies for the treatment of patients with clear cell kidney cancer. This study looked at the effectiveness of combinations of pembrolizumab (an immunotherapy infusion), lenvatinib (a VEGFR TKI targeted therapy tablet), and belzutifan (a HIF-2α targeted inhibitor tablet) in advanced kidney cancer patients who had experienced disease progression on or after immunotherapy or targeted therapy. At ASCO 2023, the results from one part of this study showed that after an average follow-up time of 7 months, half of the 24 patients in the study (50%) responded to treatment and their cancer got smaller. At ASCO GU this year updated results from the targeted therapy combinations were presented (pembrolizumab plus belzutifan, lenvatinib plus belzutifan and pembrolizumab plus lenvatinib).

62 patients were in the pembrolizumab plus belzutifan group, 64 in the lenvatinib plus belzutifan group and 73 in the pembrolizumab plus lenvatinib group. Patients were followed up for about a year and a half. Nearly half of the patients responded to treatment with lenvatinib plus belzutifan, and their cancer got smaller. One patient in the group had a complete response to treatment and their cancer disappeared. The duration of this response to treatment was an average of nearly 2 years, and the time to when the treatment stopped working and the cancer started growing again was just over a year. 8 in 10 patients survived at least one year. Patients in the pembrolizumab plus belzutifan treatment group benefitted least, with only 2 in 10 patients responding to treatment and nearly 7 in 10 patients surviving for at least one year.

6 in 10 patients reported severe or life-threatening side effects in the lenvatinib plus belzutifan group. There were two treatment-related deaths in the lenvatinib plus belzutifan treatment group (stroke) and one treatment-related death in the pembrolizumab plus lenvatinib group (a hole in the food pipe). The pembrolizumab plus belzutifan combination was best tolerated (4 in 10 patients reported severe or life-threatening side effects).

Lenvatinib plus belzutifan showed long lasting anti-tumour activity and side effects were in line with those reported from previous studies. More work is needed to support the use of this combination in routine clinical practice, and a phase 3 clinical study is currently ongoing to compare the lenvatinib plus belzutifan combination in patients with advanced kidney cancer who have previously been treated with immunotherapy.

New hope for treatment of kidney cancer brain metastases

Cabozantinib shows promise for the treatment of kidney cancer brain metastases

Kidney cancer patients with spread of the cancer to the brain (brain metastases) often have poor outcomes. Despite there being significant advances in the treatment of metastatic kidney cancer, the treatment of kidney cancer that has spread to the brain remains an unmet need with few effective treatment options.

The CABRAMET study aimed to assess the effectiveness and safety of cabozantinib (a VEGFR TKI targeted therapy tablet) in patients with kidney cancer whose disease had spread to the brain.

The study included patients with advanced kidney cancer and brain metastases. These patients had at least one brain metastasis that had not been treated with surgery or radiotherapy. Patients had been treated with no more than 3 previous anti-cancer medications, excluding cabozantinib. A total of 26 patients were included in this study, and 25 patients were included in the results.

After an average of 3 years and 4 months, the average time to when the treatment stopped working and the brain metastases started growing again was a little more than 8 months, and almost half of the patients did not have their brain metastases get worse after 6 months. Furthermore, 6 in 10 patients had experienced a significant reduction in their brain metastases. This response to treatment was maintained during the follow-up period. Almost 6 in 10 patients did not have a change in their brain metastases 24 months after having a response to treatment with cabozantinib.

The CABRAMET study presented some promising information regarding the management of kidney cancer brain metastases. This goes a long way to address an unmet need in kidney cancer patients with brain metastases.

Neoadjuvant treatment for kidney cancer

Treatment of locally advanced kidney cancer patients with lenvatinib plus pembrolizumab before and pembrolizumab after surgery

The effectiveness of combinations of immunotherapy and VEGFR TKI targeted therapy is well established for advanced kidney cancer. This prompts further investigation into the potential effectiveness of these combinations of anti-cancer medications before surgery (neoadjuvant treatment). This phase 2 study aimed to look at the effectiveness of the combination of lenvatinib plus pembrolizumab before and after surgery in patients with locally advanced kidney cancer without spread of their cancer (metastases), or patients who are unsuitable for surgery to remove their kidney tumour.

Patients were treated with the lenvatinib plus pembrolizumab combination for 12 weeks (4 infusions of pembrolizumab) before surgery, followed by surgery and then 9 months (13 infusions) of pembrolizumab after surgery (adjuvant pembrolizumab).

15 patients had all 4 cycles of the combination treatment before surgery. Of these patients, more than 9 in 10 patients had surgery without delay. Of the 15 patients, 3 (20%) patients had a partial response to treatment and their tumour got smaller, and 12 (80%) patients had stable disease. None of the patients had progression of their cancer and there were no treatment-related surgical complications with the lenvatinib plus pembrolizumab combination. Furthermore, there were no new side effects reported for the lenvatinib plus pembrolizumab combination.

This study showed that neoadjuvant treatment with a combination of lenvatinib plus pembrolizumab was effective at controlling the growth of the tumour before surgery. However, long term outcomes are needed to determine the exact role of anti-cancer treatment before and after surgery (perioperative treatment) in the management of locally advanced kidney cancer.

The gut microbiome and the effectiveness of immunotherapies

abstract 543

Can gut bacteria boost the effectiveness of the cabozantinib plus nivolumab combination?

The study of the gut microbiome in cancer patients came about because it was noticed that people who were given antibiotics while also taking immunotherapy had worse responses to treatment than people who did not take antibiotics. This might be because the antibiotics change the type of bacteria in the gut, which in turn affects how the gut immune system functions. These changes impact how the entire immune system can fight not only bacteria, but cancer.

Recent evidence suggests that the bacteria in the gut (the gut microbiome) interacts with immunotherapy in metastatic kidney cancer. The bacterium Clostridium butyricum, which produces a substance called butyrate, has been investigated to see if it can modify the bacteria in the gut. Clinical outcomes in patients with metastatic kidney cancer being treated with the immunotherapy medicines, nivolumab plus ipilimumab, were looked at. Clostridium butyricum is the key bacterium in CBM588.

Some earlier studies using the probiotic bacterium, CBM588, seemed to improve the response to immunotherapy in people taking antibiotics.

In an early study, CBM588 given together with cabozantinib plus nivolumab showed that CBM588 improved clinical benefit in previously untreated patients with metastatic kidney cancer. The current study provides updated clinical information on the potential benefits of CBM588 when given with cabozantinib plus nivolumab.

A total of 30 patients were treated with either cabozantinib plus nivolumab alone (10 patients) or together with CBM588 (20 patients). Five patients had sarcomatoid kidney cancer and two had papillary kidney cancer.

After just over 2 years follow up, response to treatment was significantly higher in the group of patients given CBM588, compared to cabozantinib plus nivolumab without CBM588 (8 in 10 patients responded compared to 2 in 10). 9 in 10 patients treated with cabozantinib plus nivolumab together with CBM588 had a reduction in the size of their tumour, compared to 8 in 10 patients treated with cabozantinib plus nivolumab without CBM588, with tumours decreasing in size on average by 51% and 22%, respectively.

This benefit from treatment lasted for at least 6 months was achieved in 8 in 10 patients given CBM588 and 6 in 10 patients treated with cabozantinib plus nivolumab alone.

The rate of severe or life-threatening treatment-related side effects was similar for both groups of patients. The most common side effects were liver problems (high levels of liver enzymes in the blood), high blood pressure, and diarrhoea, with no significant differences between the groups. No new side effects were reported.

The addition of CBM588 to the cabozantinib plus nivolumab combination continues to show promising effectiveness in patients with metastatic kidney cancer, with improved response to treatment and survival. Side effects of CBM588 are in line with those reported from previous studies. These results support larger studies in more patients with CBM588. Further work is ongoing to try to find out how CBM588 improves clinical benefits.

Acknowledgements:

Editor: Dr Elshad Hasanov (USA)
Co-editor: Dr Yusuf Acikgoz (USA)
Medical Reviewers: Professor Axel Bex (NL/UK) & Dr Eric Jonasch (US)
Medical Writer: Dr Sharon Deveson Kell (UK)