Editor’s Note: In recent years, significant progress has been made in the treatment of renal cell carcinoma (RCC). However, selecting the appropriate treatment strategy remains a critical challenge. Traditional tumor markers have limited predictive value in RCC, making the search for new and reliable biomarkers to guide treatment decisions a hot topic in RCC research. As one of the major oncology events of 2024, the ASCO Annual Meeting is set to take place soon. Oncology Outlook has invited Professor Guohai Shi from Fudan University Cancer Hospital to share the major research findings on kidney cancer biomarkers that will be presented at the conference.
Biomarker Analysis of Circulating Kidney Injury Molecule-1 (KIM-1) in IMmotion010: A Randomized Phase 3 Study of Adjuvant Atezolizumab for High-Risk Renal Cell Carcinoma After Nephrectomy (Abstract 4506)
Background: The IMmotion010 study showed that adjuvant atezolizumab did not prolong DFS in patients after nephrectomy (HR 0.93; 95% CI 0.75-1.15; P=0.50). Exploratory analysis of circulating protein biomarkers could identify high-risk patients with minimal residual disease (MRD) who might benefit from atezolizumab treatment.
Methods: Patients with clear cell RCC or sarcomatoid RCC and high recurrence risk post-nephrectomy were randomized (1:1) to receive atezolizumab 1200 mg or placebo every 3 weeks for 16 cycles or 1 year. Retrospective proteomics analysis using a platform extending analysis to ~3000 analytes was performed. High-sensitivity electrochemiluminescence technology (ECL) was used to assess KIM-1 levels in baseline and post-treatment serum samples, a membrane glycoprotein overexpressed in ccRCC and papillary RCC. Outcomes were analyzed for patients with high (≥86 pg/mL) and low baseline KIM-1 levels.
Results: In 73 patients available for PEA detection, circulating KIM-1 was significantly higher at recurrence than at baseline. Among 778 patients enrolled in IMmotion010, 752 (97%) had baseline KIM-1 data (high level: 300, 40%; low level: 452, 60%). High KIM-1 levels were associated with reduced DFS. Patients with high KIM-1 levels had better DFS with atezolizumab compared to placebo. Longitudinal analysis showed that on day 1 of cycle 4, the proportion of patients with a ≥30% increase in KIM-1 levels from baseline was 9% (12/138) in the atezolizumab group and 26% (36/141) in the placebo group for high KIM-1 levels, and 16% (34/213) and 12% (25/207) respectively for low KIM-1 levels. A ≥30% increase in KIM-1 was associated with poorer DFS, both for high KIM-1 patients (atezolizumab HR 1.68; placebo HR 3.53) and low KIM-1 patients (atezolizumab HR 3.56; placebo HR 3.22). In patients with matched ECL samples (n=103), median KIM-1 levels at recurrence (172 pg/mL) were higher than baseline (79 pg/mL).
Conclusion: Baseline high KIM-1 levels were associated with poor prognosis, but atezolizumab improved clinical outcomes compared to placebo. Post-treatment increases in KIM-1 levels were associated with poorer DFS. These data suggest that circulating KIM-1 may be a non-invasive biomarker of MRD and disease recurrence and is associated with benefit from adjuvant atezolizumab in RCC, warranting further exploration in RCC adjuvant therapy.
As research on advanced RCC progresses, with increasing drug options and extended survival times, advanced RCC is entering an era of “chronic disease.” How to rationally arrange sequential and combination treatments becomes a key focus and challenge in future clinical work. These abstracts presented at the conference show promising findings, encouraging further related clinical research. However, most data are from international sources, lacking data specific to Chinese patients. Our center has conducted multiple clinical studies on advanced RCC and designed many related biomarker studies, aiming to find specific targets for Chinese patients to improve the efficacy of advanced RCC treatment and minimize adverse reactions.
