Assessing Time to Metastatic Disease as a Proxy for Overall Survival in a Real-World Pan-Tumor Cohort

OBJECTIVES: Overall survival (OS) is the gold standard for clinical outcomes for oncology real-world evidence (RWE) studies but requires substantial follow-up, particularly in early-stage disease. Intermediate endpoints based on response assessments often require access to unstructured electronic health record (EHR) data. Alternatively, time from initial diagnosis to metastatic disease or death (TTMd) is widely available using structured EHR fields. To understand the potential of TTMd as a proxy endpoint, we assessed the relationship between TTMd and OS among patients with several solid tumor types in the community oncology setting.
METHODS: This was a retrospective cohort study of patients with Stage II or III head & neck squamous cell carcinoma (HNSCC); non-small cell lung cancer (NSCLC); triple-negative (TN) or hormone receptor-positive (HR+) breast cancer (BC); gastric/esophageal, bladder or kidney cancer; or melanoma. Patients were indexed at first visit within The US Oncology Network or non-Network practices between 1/1/17 and 12/31/22 and followed through 11/30/24. The relationship between TTMd and OS from index was assessed using Kendall τ rank correlation, overall and by tumor type.
RESULTS: Overall, 31,455 patients were included in the study (34%, HR+BC; 26% NSCLC, 13% TNBC, 9% bladder, 8% melanoma, 5% HNSCC, 3% kidney, 2% gastric/esophageal). In the cohort, 7,925 OS events were observed, and 8,808 TTMd events, of which 25% (n=2,241) were metastatic disease events. Median TTMd and OS ranged from 22-74 and 25-83 months, respectively, except in the analysis of BC cohorts, where the median was not reached. Kendall’s τ was 0.98 overall and 0.96-0.99 by tumor type.
CONCLUSIONS: TTMd was very strongly associated with OS with nearly perfect correlation observed across multiple solid tumors. TTMd should be further explored as a proxy endpoint for OS in RWE studies of early-stage cancer as a way to advance an earlier understanding of patient prognosis.