Dr Saliby on the Correlation Between Intermediate End Points and OS in Metastatic RCC

Renee Saliby, MD, MSc, postdoctoral research fellow, Dana-Farber Cancer Institute, discusses the correlation between intermediate endpoints and overall survival (OS) in patients with metastatic renal cell carcinoma (RCC) treated with immune checkpoint inhibitors.

In a retrospective study, Saliby and colleagues assessed how intermediate clinical trial end points such as objective response rate, time to treatment failure (TTF), and time to next therapy (TTNT) were associated with OS in patients with metastatic RCC who were treated with immune checkpoint inhibitor–based combinations in the frontline setting. The study included data for 1684 patients who received first-line treatment with an immune checkpoint inhibitor–containing combination between 2013 and 2023. The majority of patients (67.9%) received nivolumab (Opdivo) plus ipilimumab (Yervoy). At 21.1%, pembrolizumab (Keytruda) plus axitinib (Inlyta) was the most common immune checkpoint inhibitor/TKI combination in this patient population.

Findings presented at the 2024 Kidney Cancer Research Summit showed that TTNT had the strongest association with OS, which demonstrated a Kendall’s tau correlation of 0.67 (95% CI, 0.64-0.69). The Kendall’s tau correlation for TTF with OS was 0.49 (95% CI, 0.45-0.52). Notably, these correlations were consistent across patients with International Metastatic RCC Database Consortium favorable-, intermediate-, and poor-risk disease.

Saliby also explains that this analysis included landmark assessments at specific time points to evaluate the correlation between response and OS. Significant associations were revealed for responders vs non-responders (odds ratio [OR], 2.77; 95% CI, 2.16-3.55).

Saliby notes that this association with OS was particularly strong in the subgroups of responders receiving dual immune checkpoint inhibition with nivolumab (Opdivo) plus ipilimumab (Yervoy; OR, 3.35; 95% CI, 2.46-4.54). These findings align with the established understanding that responders to nivolumab and ipilimumab generally exhibit durable responses, which lead to enhanced OS rates, Saliby says. Additionally, transitioning to second-line therapy after initial treatment failure was associated with a positive impact on OS, Saliby continues, reinforcing the importance of effective treatment strategies beyond the first line.