In a retrospective review reported in The Lancet Oncology, Gharzai et al identified intermediate clinical endpoints that may serve as surrogates for overall survival in trials assessing definitive treatment of patients with p16-positive oropharyngeal squamous cell carcinoma.
Study Details
The study included data from five multicenter, randomized trials (NRG/RTOG 9003, 0129, 0234, 0522, and 1016) that examined radiotherapy with or without chemotherapy in patients with p16-positive localized head or neck squamous cell carcinoma.
Intermediate clinical endpoints that were tested as potential surrogates for overall survival in patients with oropharyngeal squamous cell carcinoma included the following:
- Freedom from local disease progression
- Freedom from regional disease progression
- Freedom from distant metastasis
- Freedom from locoregional disease progression
- Freedom from any disease progression
- Locoregional progression-free survival
- Progression-free survival
- Distant metastasis–free survival.
Surrogacy was evaluated under two conditions: condition 1 required high correlation between the intermediate clinical endpoint and overall survival at the patient level; condition 2 required high correlation between the treatment effect on the intermediate clinical endpoint and the treatment effect on overall survival. For both conditions, an r² > 0.7 was defined as the criterion for clinically relevant surrogacy.
Key Findings
The patient-level meta-analysis included 1,373 patients with oropharyngeal cancer. Median follow-up was 4.2 years (interquartile range = 3.1–5.1 years).
For the first condition (correlating the intermediate clinical endpoints with overall survival at the patient level), the endpoints of locoregional progression-free survival (r² = 0.72), distant metastasis–free survival (r² = 0.83), and progression-free survival (r² = 0.70) were found to be highly correlated with overall survival.
For the second condition at the trial level (correlating treatment effects of the intermediate clinical endpoints and overall survival), the endpoints of locoregional progression-free survival (r² = 0.88), distant metastasis–free survival (r² = 0.96), and progression-free survival (r² = 0.92) remained strong surrogates for overall survival. Other potential surrogates that exceeded the r2 threshold were freedom from local disease progression (r² = 0.84) and freedom from locoregional disease progression (r² = 0.76).
The investigators concluded: “We identified locoregional progression-free survival, distant metastasis–free survival, and progression-free survival as surrogates for overall survival in p16-positive oropharyngeal cancers treated with chemotherapy or radiotherapy, which could serve as clinical trial endpoints.”
Matthew J. Schipper, PhD, of the Department of Radiation Oncology, University of Michigan, Ann Arbor, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by NRG Oncology Operations, NRG Oncology SDMC, National Cancer Institute, Eli Lilly, Aventis, and others. For full disclosures of the study authors, visit thelancet.com.
