Lead Investigator: Raquibul Hannan, UT Southwestern Medical Center
Title of Proposal Research: Long-term outcomes of renal cell carcinoma patients with stable and progressive disease following treatment with Ipilimumab and Nivolumab in randomized controlled trial
Vivli Data Request: 8562
Funding Source: None
Potential Conflicts of Interest: None
Summary of the Proposed Research:
A large proportion of metastatic RCC (mRCC) patients undergoing frontline Ipilimumab/Nivolumab (Ipi/Nivo) develops stable disease (SD) or progressive disease (PD). For those experiencing a complete response (CR), induction Ipilimumab (Ipi)/ Nivolumab (Nivo) followed by maintenance Nivo results in overall survival (OS) rates of 97% at 4 years. However, CR rates occur in ~10% of patients. Survival rates plumet in patients with progressive disease (PD) and even for patients who are SD. Despite Nivo maintenance, patients with SD after induction (36%) show significantly reduced 4-year OS rates (55% vs 97%). While by comparison to PD patients (OS rates ~20%), patients with SD derive some benefit from ICI, the full potential of immunotherapy is not realized. Therefore, these patients will likely benefit from additional immune-stimulating treatments added to maintenance Nivo and provides an ideal population to design trials based on initial response to Ipi/Nivo. To design a smaller single arm phase 2 trial using Checkmate 214 SD patients as the historic control to improve upon, it would be important to know the details on RECIST measurements (exact % increase or decrease in SLD from baseline) for the SD patients at baseline and at all follow up time points. Therefore, we are requesting all data (including RECIST measurements of SLDs) for the SD patients in Checkmate 214.
The aims and objective of this proposed research are primarily descriptive. We would like to describe and report on the long-term outcome including detailed RECIST measurements of the SD and PD patients in Checkmate 214 so that other groups (including ours) can use the data as the historic control to design single arm phase 2 trials in trying to improve the outcome of metastatic RCC patients who achieve SD or PD after initial Ipi/Nivo and goes on maintenance Nivo.
Our approach does not assume that CR, PR or SD is correlated to or a surrogate for OS. In fact, we are really not investigating the factors that predicts survival. We simply want to characterize the SD and PD populations and look for responses in these patients when maintenance Nivo is continued beyond SD/PD as was done in this study. Our assumption is that a small proportion of patients in fact do eventually become PRs even after initial PD or SD. In fact, using this data we would like to design a clinical trial where we enroll SD/PD patients after Ipi/Nivo, continue the Nivo and see if we can convert the patents to PR/CR by addition additional therapy such as SBRT. We are not investigating PFS as a surrogate for survival. Neither are we looking for factors that are associated with CR.
Requested Studies:
Nivolumab Combined With Ipilimumab Versus Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (CheckMate 214)
Data Contributor: Bristol Myers Squibb
Study ID: NCT02231749