OBR OncologyA Tale of Two ICIs: Adjuvant Pembro Ups Survival in RCC, Nivo Doesn’t

A New Chapter in RCC Treatment: Pembrolizumab’s Success and Nivolumab’s Shortfall

In a significant development reported at the 2024 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU), the contrasting outcomes of two immune checkpoint inhibitors (ICIs), pembrolizumab (Keytruda) and nivolumab (Opdivo), in the adjuvant treatment of clear cell renal cell carcinoma (ccRCC) have brought new insights into cancer therapy. Pembrolizumab demonstrated a notable survival benefit for patients at high risk of recurrence post-nephrectomy, marking a pivotal moment in the management of ccRCC. Conversely, nivolumab failed to show a significant impact in a similar setting, underscoring the complexity of cancer treatment and the need for tailored therapeutic approaches.

Key Points:

• Pembrolizumab (Keytruda) significantly increased overall survival (OS) and disease-free survival (DFS) in patients with high-risk ccRCC post-nephrectomy, while nivolumab (Opdivo) did not show a similar benefit.
• The phase 3 KEYNOTE-564 trial with pembrolizumab yielded a 38% reduction in risk for progression or death, with a 4-year OS rate of 91.2% compared to 86% in the placebo group.
• Median OS has not been reached in either the pembrolizumab or placebo groups of the KEYNOTE-564 trial, indicating prolonged survival benefits.
• Serious adverse events were more common with pembrolizumab (20.7%) compared to placebo (11.5%), with a discontinuation rate of 10% in the pembrolizumab group due to adverse events.
• The phase 3 CheckMate 914 trial of nivolumab monotherapy did not meet its primary endpoint of DFS improvement, with no significant difference from placebo.
• Subgroup analysis of the CheckMate 914 trial suggested potential benefits for patients with specific tumor characteristics such as sarcomatoid features and PD-L1 expression of 1% or higher.
• The differing outcomes between pembrolizumab and nivolumab trials highlight the uniqueness of each ICI and the importance of personalized treatment strategies in ccRCC.
• The success of pembrolizumab in the adjuvant setting may redefine the standard of care for high-risk ccRCC patients, emphasizing the value of early and effective intervention.

“Through this study, we now understand that pembrolizumab is more than just a measure to delay recurrence in kidney cancer; it is a means to significantly improve overall survival for patients. Considering that many patients with clear cell renal cell carcinoma have a high risk of recurrence leading to noncurable distant metastases, this finding is practice changing.”
– Toni K. Choueiri, MD, Director of the Lank Center for GU Oncology at Dana-Farber Cancer Institute in Boston

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