Time to Next Therapy Demonstrates Potential as an Intermediate End Point in Metastatic RCC

Time to next therapy (TTNT) demonstrated a strong association with overall survival (OS) in patients with metastatic renal cell carcinoma (RCC) previously treated with immune checkpoint inhibitor-based therapy, prompting further investigation into this potentially clinically meaningful intermediate trial end point for evaluating efficacy, according to data presented at the 2024 ASCO Annual Meeting and the 2024 Kidney Cancer Research Summit.^1,2

In a retrospective analysis of data from patients with metastatic RCC who received first-line immune checkpoint inhibitor-based therapy (n = 1667) obtained through the International mRCC Database Consortium (IMDC), the Kendall’s Tau correlation for OS was 0.49 (95% CI, 0.45-0.52) with regard to time to treatment failure and 0.67 (95% CI, 0.64-0.69) with regard to TTNT. Median follow-up was 15.4 months (IQR, 7.1-28.6).

“What we’re trying to do here [by looking] at a trial is to not wait years before we can say that this drug is going to work. [We want to be able to] have a closer look at the drug and the possible outcomes. This will hopefully lead to quicker approvals of drugs,” Renee Maria Saliby, MD, MS, emphasized in an interview with OncLive.

In the interview, Saliby, a postdoctoral Research Fellow at Dana-Farber Cancer Institute in Boston, Massachusetts, discussed results from an evaluation of intermediate end points for OS in patients with metastatic RCC with prior exposure to immune checkpoint inhibitor-based therapy, as well as highlighted the importance of expanding on this research in order to promote timely regulatory approvals.

OncLive: How has the treatment armamentarium for RCC transitioned in recent years, and how did this transition lead to your analysis?

Saliby: Recent advances since 2018 have led to an increase in OS for patients with metastatic RCC who are now receiving immune checkpoint inhibitor-based therapy. We now have median OS [that can reach] 53 months, but with that we have new challenges.

Phase 3 [confirmatory] trials now require longer follow-up, more events to happen, and more resources and costs [are needed]. Therefore, [investigators] are looking at intermediate end points and how they may be associated with OS, [giving] us an earlier look at trial outcomes.

What methods were utilized to conduct this retrospective study?

We studied patients from the IMDC, which is a database that collects information from patients with metastatic RCC. We looked at patients who received immune checkpoint inhibitor-based therapy from 2013 to 2023.

Intermediate end points that we studied were objective response assessed by trained operator, TTNT, which was the period between the start of the first and start of the second line of therapy. We also studied time to treatment failure, which is the time from the first line of therapy to when the patient stopped this therapy.

What key findings were seen from this study?

We did multiple statistical analyses to look at this association. At all time points, we saw that TTNT was strongly correlated with OS, with a very strong Kendall’s tau correlation of 0.67. We also did some landmark analyses to see if [there was] a response at 6 months [if the patient had] stopped therapy or [if they had] transitioned to a second line of therapy. [These] were associated with longer OS, and we did see very good associations there.

Obviously, patients who did respond to their first-line therapy did better in terms of OS, and we saw that specifically in the dual immune checkpoint inhibitor arm. That makes sense because we know that people who respond to nivolumab [Opdivo] plus ipilimumab [Yervoy] have durable responses and better survival.

What future directions are you hoping to see with this research?

This is a retrospective study with real-world data. Ideally, we would like bigger collaborations with bigger numbers and [more] retrospective studies. We would love to obtain data from clinical trials to be able to do further analysis and confirm these findings.

Reference

1. Saliby RM, Xie W, Wells JC, et al. Evaluating intermediate endpoints (IE) for overall survival (OS) in metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICI): an IMDC study. J Clin Oncol. 2024;42(4):400. doi:10.1200/JCO.2024.42.4_suppl.400
2. Saliby RM. Evaluating intermediate endpoints for overall survival in metastatic renal cell carcinoma treated with immune checkpoint inhibitors: an IMDC study. Presented at: 2024 Kidney Cancer Research Summit; July 11-12, 2024; Boston, MA. Abstract 20.