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

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

In recent years, the management of metastatic RCC has undergone significant changes, particularly with the introduction and widespread use of immune checkpoint inhibitors, Saliby begins. These advances have substantially improved OS rates for patients, with median OS now reaching up to 53 months, according to Saliby. However, these improvements have also introduced new challenges in clinical trial design and evaluation, she explains. Specifically, phase 3 confirmatory trials now require longer follow-up periods, more events to occur, and greater amounts of resources, Saliby notes. As a result, researchers are increasingly focusing on intermediate end points, which can provide earlier insights into trial outcomes and potentially predict long-term survival outcomes, Saliby notes.

To explore these intermediate end points and their relationship with OS, a retrospective study was conducted using data from the International Metastatic RCC Database Consortium, which tracks information on patients with metastatic RCC, Saliby continues. The study included patients who received immune checkpoint inhibitor–based therapies between 2013 and 2023. The primary intermediate end points were objective response rate, which was assessed by trained professionals; time to next treatment, defined as the interval between the start of the first and second lines of therapy; and time to treatment failure, which was defined as the duration from the initiation of the first therapy until it was discontinued, Saliby reports.

The study determined the association between these end points and OS, providing valuable insights that could help optimize treatment strategies and improve patient outcomes in the evolving metastatic RCC treatment paradigm, she states. The findings underscore the importance of early treatment response as a predictor of long-term survival, particularly in the context of immune checkpoint inhibitor–based therapies, Saliby concludes.

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Renee Saliby, MD, MSc, discusses the investigation of the correlation between intermediate end points and OS in metastatic renal cell carcinoma.

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.

 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.

Renee Saliby, MD, MSc discusses the relationship between intermediate end points and overall survival in metastatic renal cell carcinoma.

Renee Saliby, MD

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

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