ASCO 2024 Highlight: Promising RCC Biomarkers

Among a trio of biomarker studies presented at the 2024 meeting of the American Society of Clinical Oncology, one stood out as having potential predictive and prognostic value for some kidney cancer patients.

Presented by Dr. Laurence Albiges of the Institut Gustave Roussey in France, kidney injury molecule-1 (KIM-1), a protein that can be detected in a blood sample, may be a promising biomarker for predicting renal cell carcinoma (RCC) disease recurrence after surgery. [ASCO 2024, Abstract 4506]

KIM-1 could also help identify patients that might benefit from checkpoint inhibitor therapies after kidney surgery and the researchers suggested additional trials should be done to validate KIM-1 as a clinically valuable biomarker for RCC.

Albiges used the phase 3 IMmotion010 trial for this biomarker analysis. IMmotion010 randomized 778 people with RCC who had undergone kidney surgery and were at increased risk of disease recurrence to receive adjuvant treatment (given after surgery) with the PD-L1 inhibitor immunotherapy atezolizumab (Tecentriq) or placebo and investigators assessed disease-free survival (DFS) as the primary trial end point.

The investigators analyzed blood samples collected at three points: pre-treatment (considered as baseline), while patients were on treatment, and when disease recurred or if patients discontinued treatment even though disease had not recurred.

KIM-1 stood out among about 3000 proteins Albiges and her group looked at as being highly expressed at disease recurrence compared to the baseline.

KIM-1 is a cell membrane protein known to indicate the presence of clear cell RCC that might be left behind following surgery.

Albiges outlined three key results from the KIM-1 analysis that indicated it might be a promising biomarker:

• High levels of KIM-1 at baseline was associated with worse DFS. The median DFS was 35.88 months in patients with high baseline KIM-1 compared with 57.23 months in patients with low baseline KIM-1.

“This depicts the prognostic value of this circulating biomarker, and it has been previously established as well,” Albiges said.

• Atezolizumab showed improved DFS vs placebo in patients with high baseline KIM-1. Among patients with high KIM-1 at baseline, median DFS was not reached in the atezolizumab group but was 21.16 months in the placebo group. Among patients with low baseline KIM-1, median DFS was 57.23 months with atezolizumab and was not reached in the placebo group. Albiges noted this result indicated the potential predictive value of KIM-1.

• An increase in KIM-1 while patients were on treatment was associated with worse DFS in patients with either high or low KIM-1 at baseline.

While the IMmotion010 trial used atezolizumab, Dr. Wenxin Xu of the Dana-Farber Cancer Institute, who discussed the three biomarker trials, noted that there is yet no data with pembrolizumab (Keytruda), which is the current standard of care.

However, KIM-1 stands out as a potential biomarker to identify patients with minimal residual disease after resection who may have increased risk of recurrence and could benefit more from adjuvant PD-L1 treatment, and both Albiges and Xu said it is ready for validation studies.

The other two biomarker analyses were based on the phase 3 trials CLEAR and KEYNOTE-426 comparing a combination of immunotherapy plus targeted therapy with sunitinib. [ASCO 2024, Abstract 4504] [ASCO 2024, Abstract 4505]

The CLEAR trial showed pembrolizumab plus lenvatinib (Lenvima) was superior to sunitinib in advanced RCC and KEYNOTE-426 established that combination therapy with pembrolizumab plus axitinib (Inlyta) was superior to sunitinib in advanced RCC.

Neither trial analysis identified a PD-L1 biomarker that was associated with benefit from therapy. Combination immunotherapy plus a TKI consistently outperformed sunitinib regardless of genetic or molecular subgroups, suggesting that PD-L1 biomarkers are likely not useful in selecting the most beneficial first-line therapy.

Xu noted these results are in line with existing data from previous trials assessing PD-L1 biomarker activity in patients treated with combination therapy.

“This reinforces that PD-L1 should not be routinely clinically used to deny patients from first-line combination immunotherapies,” he said.