IKCS 2022: Association Between Depth of Response (DepOR) and Clinical Outcomes: Exploratory Analysis in Patients with Previously Untreated Advanced Renal Cell Carcinoma (aRCC) in CheckMate 9ER

(UroToday.com) The second poster session at the 2022 International Kidney Cancer Symposium (IKCS): North America meeting featured a number of presentations, including one from Dr. Apolo discussing the association between depth of response and clinical outcomes among patients with advanced renal cell carcinoma (RCC).


In the CheckMate 9ER trial, patients with untreated aRCC who were treated with nivolumab plus cabozantinib (NIVO+CABO) experienced superior progression-free survival (PFS; HR, 0.56) and overall survival (OS; HR, 0.70) along with nearly double objective response and complete response (CR) rates, compared to those who received sunitinib (SUN) with extended 25.4-month minimum (32.9-month median) follow-up.

In this exploratory analysis, the authors evaluated the association between the depth of response (DepOR) and clinical outcomes in this trial.

As previously presented and published, in CheckMate 9ER, patients received NIVO (240mg) every 2 weeks plus CABO (40mg) once daily or SUN (50mg once daily; 4 weeks; 6-week cycles). For this analysis, the authors subdivided patients into DepOR subgroups, based on best overall response (blinded independent central review [BICR], RECIST v1.1) and best tumor reduction thresholds (CR; partial response subdivided by tumor reduction of ≥80% [PR1]; ≥60%-< 80% [PR2]; or < 60% [PR3]; stable disease; and progressive disease).

The authors examined PFS (per BICR) and OS stratified by DepOR subgroups, after a 6-month post-randomization landmark. Treatment-related adverse events (TRAEs) were also assessed.

At the 6-month landmark, 236 of 323 patients randomized to NIVO+CABO and 157 of 328 patients randomized to SUN were progression-free and alive. At this time, 293/323 and 253/328 were alive and categorized by DepOR in the NIVO+CABO and SUN groups, respectively.

A greater proportion of patients receiving NIVO+CABO had deeper responses versus SUN (CR, PR1, PR2).

Deeper responses with NIVO+CABO were associated with improved 12-month PFS rates versus SUN for CR (94.9% vs 82.4%), PR1 (81.3% vs 37.5%), and PR2 (72.1% vs 53.2%).
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Increasingly deeper responses led to better OS outcomes overall; yet OS rates and medians were comparable between arms for CR and PR1-3.
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No meaningful patterns for overall TRAEs by subgroup were identified.
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The authors concluded that, in the context of the CheckMate 9ER trial, more patients achieved deeper responses with NIVO+CABO versus SUN and deeper responses were generally associated with improved PFS and OS.

Presented by: Andrea Apolo, MD, National Cancer Institute, Bethesda, MD