IMmotion010 trial: KIM-1 and disease-free survival in RCC

Baseline KIM-1 expression and on-treatment increases were linked to worse disease-free survival (DFS) in patients with renal cell carcinoma (RCC) at high recurrence risk, while atezolizumab did not extend DFS compared with placebo in the overall IMmotion010 trial population.

The double-blind phase 3 IMmotion010 trial (NCT03024996) involved 778 patients with RCC from 215 clinical sites across 28 countries; patients had a clear cell or sarcomatoid component and were thus at increased recurrence risk post-nephrectomy [1]. The participants were randomised to receive adjuvant atezolizumab (n=390) or a placebo (n=388). The primary endpoint was investigator-assessed DFS in the intention-to-treat (ITT) population.

The median DFS was 57.2 months with atezolizumab compared with 49.5 months with placebo (HR 0.93; 95% CI 0.75–1.15; P=0.50). Thus, the authors concluded that atezolizumab did not significantly extend DFS compared to placebo [1]. However, Prof. Laurence Albiges (Institut Gustave Roussy, France) and colleagues conducted a retrospective analysis of circulating protein biomarkers to identify high-risk patients who might benefit from atezolizumab [2]. KIM-1 was found to be the most significantly enriched circulating protein in recurrence samples versus baseline.

The patient characteristics showed that participants could be stratified into 2 groups: KIM-1–high status: 300 participants (median age 64 years, 77% men, 63% PD-L1 positive, 16% sarcomatoid component); or KIM-1–low status: 452 participants (median age 58 years, 69% men, 59% PD-L1 positive, 11% sarcomatoid component). Most of the participants had T2/T3a disease stage (57% vs 69%) and stage III disease (83% vs 86%).

The findings showed that in KIM-1–high patients, atezolizumab improved DFS versus placebo (median DFS was not estimable [NE] vs 21.16 months; HR 0.72; 95% CI 0.52–0.99). In contrast, in KIM-1–low patients, atezolizumab did not improve DFS (median DFS was 57.23 months vs NE; HR 1.12; 95% CI 0.88–1.63). Furthermore, in the KIM-1–high group, fewer patients experienced on-treatment KIM-1 increases with atezolizumab compared with placebo (9% vs 15%). In the KIM-1–low group, the increase was similar between atezolizumab and placebo (16% vs 14%).

"On-treatment increases in KIM-1 were associated with worse DFS in both KIM-1–high and KIM-1–low subgroups," Prof. Albiges noted. The findings suggest that KIM-1 could be a valuable biomarker to identify patients who might benefit from atezolizumab, as well as for monitoring disease recurrence.

"Additional validation studies are warranted to confirm the utility of circulating KIM-1 in adjuvant RCC as a non-invasive biomarker for identification of minimal residual disease (MRD), predicting outcomes to checkpoint inhibitor treatment, and longitudinal monitoring for disease recurrence," concluded Prof. Albiges.

1. Bex A, et al. Ann Oncol. 2022;33(suppl 7):S1431-S1432.
2. Albiges L, et al. Circulating kidney injury molecule-1 (KIM-1) biomarker analysis in IMmotion010: A randomized phase 3 study of adjuvant atezolizumab vs placebo in patients with renal cell carcinoma at increased risk of recurrence after resection. Abstract 4506. 2024 ASCO Annual Meeting 2024. 31 May–4 June, Chicago, IL, USA.

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Posted on 13 June 202420 June 2024