Laurence Albiges, MD, PhD, on Renal Cell Carcinoma: Biomarker Analysis of the IMmotion010 Study
2024 ASCO Annual Meeting
Laurence Albiges, MD, PhD, of Gustave Roussy, Université Paris-Saclay, discusses phase III findings showing that high baseline serum KIM-1 levels were associated with poorer prognosis but improved clinical outcomes with atezolizumab vs placebo in patients with renal cell carcinoma at increased risk of recurrence after resection. Increased post-treatment KIM-1 levels were found to be associated with worse disease-free survival (Abstract 4506).
Transcript
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
Currently, standard of care in the adjuvant setting is pembrolizumab for patients that have had surgery and that are considered at high risk of recurrence for RCC. What we don't know is how we can better select our patients. At this recent ASCO, I had the chance to present an exploratory analysis within the IMmotion 010 study. This trial tested atezolizumab in the adjuvant setting did not demonstrate the disease-free survival benefit. But here the question is, can we do a better job with defining circulating biomarker? And so the work conducted, which is translational exploratory analysis, was a two-step process, the first one being identifying circulating proteins that were associated with an increase at time of disease recurrence. And when screening over 3000 proteins, one stands out, KIM-1, which stands for kidney injury molecule one, which clearly had an increase at the time of disease recurrence.
Then we took on to the next step, which was to assess the association of high baseline KIM-1, meaning after surgery with disease-free survival. And we confirmed that KIM-1 is a prognostic circulating biomarker that was actually already demonstrated in the past in other adjuvant studies, but it is the first time that not only we saw a prognostic value, but also a potentially predictive value. Indeed, in our data sets, not only patients with high KIM-1 had a worst disease-free survival, but atezolizumab was associated with an increased benefit with regard to disease-free survival over placebo in those patients with high baseline KIM-1. Furthermore, we showed that the kinetic of this circulating biomarker is important because any increase in this biomarker was associated with worse DFS.
Ultimately, we further validate the fact that patients at time of disease recurrence had a significant increase in KIM-1 using a different assay than the screening one. So taken all together, what these data are showing us is that circulating KIM-1 is a potential biomarker for prognostic assessment in the adjuvant space, but also potentially for the predictive use of checkpoint inhibitor in the adjuvant setting. And that actually come as a confirmation of prior work recently presented within the CheckMate 914 study as well. Of course, it will require further prospective validation, but this biomarker could help us in the setting of the adjuvant space to define a go/no-go strategy and potentially as well for monitoring patients and detect earlier recurrence. It is the first potential minimal residual disease biomarker that is being discussed in RCC.
The ASCO Post Staff
Don S. Dizon, MD, of Legorreta Cancer Center at Brown University and Lifespan Cancer Institute, discusses final phase II results of the BrUOG 354 trial showing that, for patients with ovarian and other extrarenal clear cell cancers, nivolumab and ipilimumab warrant further evaluation against standard treatment, given the historically chemotherapy-resistant nature of the disease (LBA5500).
The ASCO Post Staff
Toni K. Choueiri, MD, FASCO, of the Dana-Farber Cancer Institute, discusses phase III findings showing that, in patients with advanced renal cell carcinoma (RCC), the benefit of lenvatinib plus pembrolizumab vs sunitinib in overall response rate does not appear to be affected by such factors as gene‐expression signatures for tumor‐induced proliferation, PD‐L1 status, or the mutation status of RCC driver genes.
The ASCO Post Staff
Alicia Morgans, MD, MPH, of Dana-Farber Cancer Institute, and Karim Fizazi, MD, PhD, of Institut Gustave Roussy and the University of Paris-Saclay, discuss a second interim analysis of the health-related quality of life and pain outcomes in the PSMAfore study (Abstract 5003).
The ASCO Post Staff
Yasmin H. Karimi, MD, of the University of Michigan Comprehensive Cancer Center, discusses 2.5-year follow-up data on epcoritamab monotherapy for patients with relapsed or refractory large B-cell lymphoma. The subcutaneous regimen continues to demonstrate durable responses (Abstract 7039).
The ASCO Post Staff
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