Modest Correlation of Progression-Free and Overall Survival in Modern First-Line Metastatic Colorectal Cancer Trials


Key Points

  • Modest correlations between progression-free survival and overall survival were observed in patient-level data overall among patients treated with nonbiologic agents only and among patients receiving biologic agents.
  • Findings were similar for trial-level data.

In a study reported in the Journal of Clinical Oncology, Shi et al found a modest correlation of progression-free survival with overall survival as first-line treatment endpoints in patients with metastatic colorectal cancer.

The study involved individual patient- and trial-level data from 16,762 patients in 22 first-line metastatic colorectal cancer studies conducted between 1997 and 2006 in the Analysis and Research in Cancers of the Digestive System Database. Antiangiogenic or anti-EGFR agents were evaluated in 12 of the studies.

Overall, 44% of patients received a regimen that included biologic agents. Median first-line progression-free survival was 8.3 months, and median overall survival was 18.2 months.

Patient-Level Findings

Progression within 6 or 12 months of randomization was significantly associated with worse overall survival. However, for individual patient data, correlation between progression-free survival and overall survival was modest overall (ρ = 0.51), among patients receiving only nonbiologic agents (ρ = 0.47), and among patients receiving biologic agents (ρ = 0.55).

Similarly, correlation of progression-free survival and overall survival was modest at the trial level overall (R2WLS[weighted least squares] = 0.54, R2Copula = 0.46), in comparisons involving only nonbiologic agents (0.59 and  0.35), and in comparisons involving biologic agents (0.52 and 0.45). Correlations were similar in analyses limited to nonstrategy trials (0.54 and 0.48) and superiority trials (0.51 and 0.54).

The investigators concluded: “In modern [metastatic colorectal cancer] trials, in which survival after the first progression exceeds time to first progression, a positive but modest correlation was observed between [overall survival] and [progression-free survival] at both the patient and trial levels. This finding demonstrates the substantial variability in [overall survival] introduced by the number of lines of therapy and types of effective subsequent treatments and the associated challenge to the use of [overall survival] as an endpoint to assess the benefit attributable to a single line of therapy. [Progression-free survival] remains an appropriate primary endpoint for first-line [metastatic colorectal cancer] trials to detect the direct treatment effect of new agents.”

Daniel J. Sargent, PhD, of the Mayo Clinic, is the corresponding author for the Journal of Clinical Oncology article.

The study was supported by the Analysis and Research in Cancers of the Digestive System Foundation. For full disclosures of the study authors, visit

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