Biomarkers for treatment of renal cell carcinoma

Biomarkers are needed to guide clinical decision-making for the treatment of kidney cancer. Post-hoc analyses of several randomised-controlled trials aimed to define predictive biomarkers for first-line or adjuvant treatment of renal cell carcinoma (RCC).

Analysis of samples from the phase 3 CLEAR trial (NCT02811861) showed that first-line lenvatinib plus pembrolizumab improved objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) compared with sunitinib, regardless of PD-L1 expression, driver gene mutations (VHL, PBRM1, SETD2, BAP1, KDM5C), gene expression signature, or molecular subtype (angiogenesis/stromal, angiogenesis, immune/proliferative, proliferative, stromal/proliferative, other) [1].

Biomarker analysis from the KEYNOTE-426 trial (NCT02853331) showed that the benefit (ORR, PFS, OS) of first-line axitinib plus pembrolizumab was independent of PD-L1 expression, tumour mutations and gene expression signatures [2]. However, PBRM1-mutated tumours were found to have a significant higher ORR to pembrolizumab compared with PBRM1-wildtype tumours (P=0.002).

Proteomic analysis from the IMmotion010 trial (NCT03024996) identified post-nephrectomy kidney injury molecule-1 (KIM-1) serum levels as a potential biomarker for minimal residual disease and disease recurrence [3]. High post-nephrectomy KIM-1 serum levels were associated with worse disease-free survival. On the other hand, participants with high baseline KIM-1 serum levels showed better disease-free survival with atezolizumab versus placebo.

Based on these presentations, discussant Dr Wenxin Xu (Dana-Farber Cancer Institute, MA, USA) concluded that “PD-L1 expression, somatic tumour mutations, and gene expression signatures should not be used in clinical practice to exclude patients from receiving immune checkpoint inhibitor plus TKI combination therapies. In addition, KIM-1 should be prospectively validated as a prognostic and predictive biomarker for adjuvant immunotherapy.”

1. Choueiri TK, et al. Biomarker analyses in patients with advanced renal cell carcinoma (aRCC) from the phase 3 CLEAR trial. Abstract 4504, ASCO Annual Meeting 2024, 31 May–4 June, Chicago, IL, USA.
2. Rini B, et al. Biomarker analysis of the phase 3 KEYNOTE-426 study of pembrolizumab (P) plus axitinib (A) versus sunitinib (S) for advanced renal cell carcinoma (RCC). Abstract 4505, ASCO Annual Meeting 2024, 31 May–4 June, Chicago, IL, USA.
3. Albiges L, 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. Abstract 4506, ASCO Annual Meeting 2024, 31 May–4 June, Chicago, IL, USA.
4. Xu W. The needle in the haystack. Finding biomarkers in kidney cancer. ASCO Annual Meeting 2024, 31 May–4 June, Chicago, IL, USA.

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Posted on 18 July 202426 July 2024