Biomarker-Driven Approaches Could Refine Treatment Selection in RCC

Emre Yekedüz, MD

Integrating biomarker-driven approaches into treatment decision-making process for patients with renal cell carcinoma (RCC) could help clarify therapy selection, according to Emre Yekedüz, MD, who highlighted data for one potential biomarker: KIM-1.

At the 2024 ASCO Annual Meeting, investigators shared data from an exploratory analysis of the phase 3 IMmotion010 trial (NCT03024996), which evaluated atezolizumab (Tecentriq) vs placebo for the adjuvant treatment of patients with resected intermediate- to high-risk RCC.

Findings from the retrospective exploratory analysis showed that high KIM-1 serum levels were associated with poorer disease-free survival (DFS), irrespective of trial treatment. Patients with high KIM-1 levels at baseline (n = 300) experienced a median DFS of 35.88 months vs 57.23 months for those with low KIM-1 levels at baseline (n = 452; HR, 1.75; 95% CI, 1.40-2.17).

Furthermore, in patients with high KIM-1 levels, the median DFS was not estimable (NE) in those treated with atezolizumab (n = 151) vs 21.16 months with placebo (HR, 0.72; 95% CI, 0.52-0.99). In the subgroup of patients with low KIM-1 levels, the median DFS was 57.23 months for atezolizumab (n = 229) vs NE for placebo (n = 223; HR, 1.12; 95% CI, 0.88-1.63).

“We classify our patients according to their clinical risk. Some patients may be overtreated,” Emre Yekedüz, MD, explained in an interview with OncLive®. “If we use biomarkers, we can more accurately select patients to get more benefit from the immunotherapy and other combination therapies in the adjuvant setting, as well as the metastatic setting.”

In the interview, Yekedüz, a research fellow at Dana-Farber Cancer Institute in Boston, Massachusetts, discussed recent advances in the RCC paradigm, highlighted the need for biomarkers to help inform treatment strategies, and detailed novel treatments and combinations—such as HIF2α inhibitors and immuno-oncology (IO) agents—being explored for this patient population.

OncLive: How could the use of IO-based regimens continue to shape the RCC treatment paradigm?

Yekedüz: In the last decade, we have had great advances in the treatment of [RCC], especially in metastatic setting. Immunotherapy-based combinations—IO/IO or IO/TKI regimens—have improved the survival outcomes in patients with metastatic RCC.

In the pipeline, we are waiting for other drugs, especially HIF2α inhibitors. Belzutifan [Welireg] was the first HIF2a inhibitor [approved by the FDA for the treatment of patients with advanced RCC following a PD-1/PD-L1 inhibitor and a VEGF TKI]. We are waiting on data for new combinations with IO-based regimens featuring belzutifan and other HIF2α inhibitors. This is an exciting area for our patients, and we are expecting more [data] in the near future.

Were there any important data in RCC to emerge from the 2024 ASCO Annual Meeting?

At the 2024 ASCO Annual Meeting, [data] from several biomarker studies [were presented]; unfortunately, most of them were negative studies. However, the KIM-1 molecule seems to be associated with a higher risk of [recurrence in patients with RCC]. These [findings] came from the IMmotion010 trial and were presented by Laurence Albiges, MD, PhD, [of Gustave Roussy Institute in Villejuif, France]. This is an important topic because these types of biomarkers can be helpful for select patients who will [gain] more benefit from immunotherapy or combination therapies.

What are the key things to watch in ongoing research in RCC?

The future is bright in kidney cancer. We are now waiting for triplet therapies in the metastatic setting, as well as other new combination therapies, such as IO plus HIF2α inhibitors, in the adjuvant setting. We are excited for the upcoming results [and using those data] to help treat our patients.

Reference

Albiges L, Bex A, Suárez C, et al. Circulating kidney injury molecule-1 (KIM-1) biomarker analysis in IMmotion010: A randomized phase 3 study of adjuvant (adj) atezolizumab (atezo) vs placebo (pbo) in patients (pts) with renal cell carcinoma (RCC) at increased risk of recurrence after resection. J Clin Oncol. 2024;42(suppl 16):4506. doi:10.1200/JCO.2024.42.16_suppl.4506