KEY TAKEAWAYS
- The CheckMate142 phase 2 trial aimed to investigate the patient-level correlation between PFS and OS in MSI-H/dMMR mCRC treated with NIVO or NIVO+IPI.
- The endpoints were to determine PFS and OS.
- The strong correlation between PFS and OS validates PFS as a surrogate endpoint in MSI-H/dMMR mCRC immunotherapy.
Validation of surrogate endpoints for overall survival (OS) requires strong association at both the individual and trial levels.
Ashley E. Tate and the team investigated the patient-level correlation between progression-free survival (PFS) and OS among patients with microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer (MSI-H/dMMR mCRC) treated with nivolumab (NIVO) or nivolumab plus low-dose ipilimumab (NIVO+IPI) in the phase II CheckMate 142 study.
They performed an inclusive analysis of correlation in the previously treated NIVO cohort (74 patients, 69.5 months median follow-up), combined treatment-naïve and previously treated NIVO+IPI cohorts (164 patients, 62.8 months median follow-up), and treatment-naïve NIVO+IPI cohort (45 patients, 52.6 months median follow-up).
Copula functions (Clayton, Frank, Hougaard, Joe, and Plackett) were utilized to model PFS-OS dependence, with PFS and OS curves represented by commonly used parametric distributions. Evaluation of joint PFS-OS models included statistical goodness-of-fit criteria, visual fit to Kaplan-Meier curves, and assessment of clinical plausibility for survival extrapolations beyond the follow-up period. Spearman’s rho was employed to measure correlation strength.
They found that Spearman’s rho estimates ranged from 0.80 to 0.89 for the NIVO cohort, 0.82 to 0.96 for the combined NIVO+IPI cohorts, and 0.82 to 0.95 for the treatment-naïve NIVO+IPI cohort. Selected copula models yielded Spearman’s rho estimates of 0.83 (95% CI: 0.73-0.89) for NIVO, 0.85 (95% CI: 0.77-0.90) for combined NIVO+IPI, and 0.92 (95% CI: 0.78-0.98) for treatment-naïve NIVO+IPI. Across NIVO and combined NIVO+IPI cohorts, the lower bound of the 95% CI for Spearman’s rho exceeded 0.7, confirming robust evidence of strong correlation between PFS and OS.
The study concluded that the strong patient-level correlation between PFS and OS in all cohorts of the CheckMate-142 study supports the validation of PFS as a suitable surrogate endpoint for OS in patients with MSI-H/dMMR mCRC receiving immunotherapy.
The trial was sponsored by the Bristol-Myers Squibb.
Source: https://cslide.ctimeetingtech.com/esmogi24hybrid/attendee/confcal/show/session/3
Clinical Trial: https://clinicaltrials.gov/study/NCT02060188
Tate A.E., Roodhart J.M, Sharpe D.J., et al. (2024). “Evaluating the patient-level association between progression-free survival and overall survival in microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer (MSI-H/dMMR mCRC) treated with immune checkpoint inhibitors.” Presented at ESMO-GI 2024 (Abstract 57P).
