Advances in mRCC Treatment and Study Background

The past decade has brought significant advancements in mRCC treatment, especially with the introduction of IO-based therapies. Yet, even with multiple approvals for IO combinations, debate remains on which regimen offers the most effective 1L therapy. LARVOL’s study addresses this by comparing the efficacy of IO combinations, drawing on the latest data released in 2024. Our goal is to provide insight into how these therapies affect progression-free survival (PFS) and overall survival (OS) in patients.

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Methods and Approach

Our meta-analysis used data from LARVOL CLIN, focusing on five key clinical trials that compared various IO combinations against sunitinib, a standard tyrosine kinase inhibitor (TKI) used in mRCC treatment. Each of the trials assessed PFS as the primary endpoint, with some also measuring OS. The trials examined distinct approaches, including combinations of two IO agents or an IO paired with a TKI, providing a broad view of 1L options for mRCC.

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Key Findings and Trial Highlights

Among the trials reviewed, the CLEAR trial stood out for its analysis of pembrolizumab combined with lenvatinib. This combination showed the most significant improvement in PFS, highlighting its potential as a leading 1L therapy choice. For trials that measured OS as a coprimary outcome, many demonstrated significant survival improvements, suggesting that IO-based regimens may effectively extend patient lifespans.

However, not all trials showed uniform results. For instance, the JAVELIN Renal 101 trial, which tested avelumab and axitinib, did not achieve a statistically significant OS benefit over sunitinib in its final analysis, despite initial promising data. This finding underscores the variability in IO combination efficacy, emphasizing the need for ongoing study in this evolving field.

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‍Implications for the Future of mRCC Treatment

The FDA’s first approval of an IO combination for 1L mRCC was based on the CheckMate 214 trial, setting the stage for ongoing exploration of IO regimens. Our research suggests that dual IO and IO-plus-TKI combinations provide substantial benefits over sunitinib, indicating a potential shift away from sunitinib as the gold standard for 1L mRCC. However, as shown by the latest updates from JAVELIN Renal 101, not all combinations achieve the same OS benefits, highlighting the importance of selecting the most effective approach.

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Conclusion: Looking Forward

Our team is thrilled to present this work at SITC 2024, contributing to the expanding knowledge of mRCC treatment. As the landscape of cancer therapy advances, we aim to offer data-driven insights that can guide clinicians toward more effective patient care.

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Stay tuned for updates as we share more from the conference and continue our commitment to improving cancer treatment through rigorous research and innovation.

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