ESMO 2024 Kidney Cancer Highlights

We rounded up a few research highlights from the 2024 Congress of the European Society for Medical Oncology (ESMO), held recently in Madrid, Spain.

Belzutifan continues to outperform targeted therapy in advanced kidney cancer

Belzutifan outperformed targeted therapy with everolimus in certain advanced kidney cancer patients, who experienced longer times till their tumors began growing again with the novel hypoxia-inducible factor 2a (HIF-2a) inhibitor, according to the final analysis of the phase 3 LITESPARK-005 study. [ESMO 2024, Abstract LBA74]

The progression-free survival (PFS) was similar with both treatments – 5.6 months after a median 36 months of follow up. But the PFS rate (meaning the percentage of people likely to remain stable without disease progression after a specified amount of time) after 12 and 24 months was higher in the belzutifan arm – 33.7% and 17.5%, respectively, compared with 17.6% and 4.1% with everolimus.

In addition, more people responded to belzutifan than to everolimus, with objective response rates (ORR) of 22.7% versus 3.5%, respectively, and more people had to stop treatment due to side effects if they were taking everolimus, although the number of serious side effects was similar between groups.

“At the final analysis of the phase 3 LITESPARK-005 study, belzutifan continued to show PFS and ORR benefits vs everolimus, including durable responses lasting over 2 years,” said lead researcher Dr. Brian Rini, Chief of clinical trials at Vanderbilt-Ingram Cancer Center in Nashville, Tennessee and member of the KCA’s Medical Steering Committee. “With over 2 years of minimum follow-up, more participants remained on treatment with belzutifan vs everolimus, [but] significant improvement in OS was not observed.”

LITESPARK-005 included 746 advanced clear cell RCC patients who had received prior treatment randomly selected to receive either belzutifan or everolimus.

Earlier results of the trial led to FDA approval of belzutifan to treat advanced RCC following treatment with immunotherapy or targeted therapy. Belzutifan blocks HIF-2a, a protein sensitive to cellular oxygen levels and is part of pathways that can favor tumor growth, especially in people with kidney cancer with von Hippel-Lindau (VHL) gene mutations.

Patients respond to a new HIF-2a drug

NKT-2152 is a new HIF-2a inhibitor and early results from a phase 1/2 trial showed that advanced kidney cancer patients responded to treatment, making it a potential new therapeutic option. [ESMO 2024, Abstract 1690O]

The study included 113 advanced clear cell RCC patients who had previously been treated with primarily VEGFR TKIs, which are targeted therapies that prevent blood vessel growth, and immunotherapy. After an average one-year follow up, the objective response rate was 20-26%, including one patient who had a complete response. Common side effects included anemia and fatigue.

NKT-2152 follows the success of belzutifan, which was the first HIF-2a inhibitor to show efficacy in treating advanced kidney cancer and received FDA approval in 2023.

Non-clear cell kidney cancers respond better to combination immunotherapy

Patients with non-clear cell kidney cancer – which accounts for X of all kidney cancer treatments – had survival benefits with an immunotherapy duo – ipilimumab plus nivolumab – compared to standard of care.

The phase 2 SUNNIFORECAST is the first randomized controlled trial comparing combination immunotherapy to standard of care in this patient population. [ESMO 2024, Abstract LBA75]

The trial randomly assigned 309 people with non-clear cell kidney cancers to treatment with ipilimumab plus nivolumab or standard of care – typically a VEGF TKI targeted therapy or a targeted therapy plus immunotherapy combination, although some patients received other treatment or no treatment. Most diagnoses were papillary RCC, with some chromophobe RCC, translocation RCC, and collecting duct kidney cancer. Other rarer subtypes were also represented.

Overall survival rate after one year was almost 90% in the immunotherapy group compared with 75% in the standard of care group. Average overall survival time was also longer in the immunotherapy group, especially in high-risk papillary patients, though progression-free survival and treatment response were not different between the groups.

Up to a quarter of all kidney cancer diagnoses are several kidney cancer types that are not clear cell renal cell carcinoma including chromophobe RCC, papillary RCC, and renal medullary carcinoma. People with non-clear cell RCC diagnoses typically have worse outcomes because these cancers are less understood, have fewer treatment options, and fewer opportunities to participate in clinical trials.

Injectable nivolumab could change how immunotherapy is given

An injectable form of the immunotherapy nivolumab performed as effectively and safely as nivolumab delivered intravenously via infusions, signaling a potential new way to administer this treatment that could improve both the patient experience and hospital efficiency, according to research lead by Dr. Laurence Albiges of the Institute Gustave Roussy in France and a member of the KCA’s Board of Directors. [ESMO 2024, Abstract 1691P]

Subcutaneous nivolumab (nivo SC) is given as an injection under the skin and could potentially be administered more conveniently and quickly to patients versus traveling to an infusion center to receive the treatment in its current formulation.

Results from the phase 3 CheckMate 67T trial of 495 patients showed that treatment response was comparable between two groups of previously treated advanced or metastatic RCC patients randomly assigned to either the nivo SC or intravenous nivolumab (nivo IV).

Objective response rate was 26.6% and 20.6% in the nivo SC and nivo IV arms, respectively. Disease control rate, time to response, progression-free survival, and overall survival was also similar over the updated 15 months of follow up, as were the number and severity of side effects.

Of note is the time it takes to inject nivo SC, which can last about 5 minutes. The price per treatment may also differ between the formulations.

Nivo SC awaits approval from the FDA. Subcutaneous formulations of other immunotherapies such as pembrolizumab are in development.