Correlation Between Surrogate End Points and Overall Survival in a Multi-institutional Clinicogenomic Cohort of Patients With Non–Small Cell Lung or Colorectal Cancer

Key Points

Question

What surrogate end point for capturing worsening disease is most correlated with overall survival (OS) in large linked clinicogenomic data sets?

Findings

In this cohort study of patients with non–small cell lung cancer or colorectal cancer who initiated systemic therapy for advanced disease, progression-free survival based on both radiologist and medical oncologist assessment was more consistently correlated with OS than other candidate end points, including time to treatment discontinuation and time to next treatment.

Meaning

This study suggests that, based on its correlation with OS, progression-free survival based on both radiologist and medical oncologist assessment may be an optimal surrogate end point for analysis of observational clinicogenomic data in cancer research.

Abstract

Importance

Contemporary observational cancer research requires associating genomic biomarkers with reproducible end points; overall survival (OS) is a key end point, but interpretation can be challenging when multiple lines of therapy and prolonged survival are common. Progression-free survival (PFS), time to treatment discontinuation (TTD), and time to next treatment (TTNT) are alternative end points, but their utility as surrogates for OS in real-world clinicogenomic data sets has not been well characterized.

Objective

To measure correlations between candidate surrogate end points and OS in a multi-institutional clinicogenomic data set.

Design, Setting, and Participants

A retrospective cohort study was conducted of patients with non–small cell lung cancer (NSCLC) or colorectal cancer (CRC) whose tumors were genotyped at 4 academic centers from January 1, 2014, to December 31, 2017, and who initiated systemic therapy for advanced disease. Patients were followed up through August 31, 2020 (NSCLC), and October 31, 2020 (CRC). Statistical analyses were conducted on January 5, 2021.

Exposures

Candidate surrogate end points included TTD; TTNT; PFS based on imaging reports only; PFS based on medical oncologist ascertainment only; PFS based on either imaging or medical oncologist ascertainment, whichever came first; and PFS defined by a requirement that both imaging and medical oncologist ascertainment have indicated progression.

Main Outcomes and Measures

The primary outcome was the correlation between candidate surrogate end points and OS.

Results

There were 1161 patients with NSCLC (648 women [55.8%]; mean [SD] age, 63 [11] years) and 1150 with CRC (647 men [56.3%]; mean [SD] age, 54 [12] years) identified for analysis. Progression-free survival based on both imaging and medical oncologist documentation was most correlated with OS (NSCLC: ρ = 0.76; 95% CI, 0.73-0.79; CRC: ρ = 0.73; 95% CI, 0.69-0.75). Time to treatment discontinuation was least associated with OS (NSCLC: ρ = 0.45; 95% CI, 0.40-0.50; CRC: ρ = 0.13; 95% CI, 0.06-0.19). Time to next treatment was modestly associated with OS (NSCLC: ρ = 0.60; 0.55-0.64; CRC: ρ = 0.39; 95% CI, 0.32-0.46).

Conclusions and Relevance

This cohort study suggests that PFS based on both a radiologist and a treating oncologist determining that a progression event has occurred was the surrogate end point most highly correlated with OS for analysis of observational clinicogenomic data.

Abstract

This cohort study measures associations between candidate surrogate end points and overall survival in a multi-institutional clinicogenomic data set of patients with non–small cell lung cancer (NSCLC) or colorectal cancer.