In a U.S. Food and Drug Administration (FDA) pooled analysis reported in The Lancet Oncology, Bernardo Haddock Lobo Goulart, MD, and colleagues found that response rate and progression-free survival were only moderately correlated with overall survival in first-line immunotherapy trials for metastatic non–small cell lung cancer (NSCLC).
Bernardo Haddock Lobo Goulart, MD
Study Details
The pooled analysis comprised first-line randomized trials (including patients aged ≥ 18 years with metastatic squamous and nonsquamous NSCLC) submitted to the FDA between June 2016 and March 2021. Eligible trials evaluated at least one immune checkpoint inhibitor in the experimental group vs chemotherapy in the control group.
Key Findings
A total of 13 trials including 9,285 patients evaluated immune checkpoint inhibitors alone or in combination with chemotherapy vs chemotherapy alone. At the trial level, the R2 values were 0.61 (95% confidence interval [CI] = 0.32–0.84) for correlation of overall response rate with overall survival and 0.70 (95% = 0.40–0.89) for correlation of progression-free survival with overall survival. Correlations were weak to moderate in analysis according to PD-L1 expression and were consistent across trials of immune checkpoint inhibitors alone or combined with chemotherapy.
At the patient level, among all patients, responders had longer overall survival vs nonresponders (hazard ratio [HR] = 0.28, 95% CI = 0.26–0.30), including among patients in trials evaluating immune checkpoint inhibitors in combination with chemotherapy (HR = 0.32, 95% CI = 0.29–0.34) and among patients in trials evaluating immune checkpoint inhibitors alone (HR = 0.24, 95% CI = 0.22–0.26). Among responders, overall survival was longer in patients from the immune checkpoint inhibitor alone or with chemotherapy groups vs chemotherapy groups (HR = 0.54, 95% CI = 0.48–0.61). No apparent difference in survival was observed between nonresponders in the two groups.
The investigators concluded, “Correlations of overall response rate and progression-free survival with overall survival were generally moderate in this pooled analysis. The findings support routine analysis of mature overall survival data, where feasible, in first-line randomized trials of immune checkpoint inhibitors for metastatic NSCLC.”
Dr. Goulart, of the Office of Oncologic Diseases, U.S. Food and Drug Administration, Silver Spring, MD, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by the U.S. Food and Drug Administration. For full disclosures of the study authors, visit thelancet.com.
