Progression-free survival as a potential surrogate end point for overall survival in advanced cervical carcinoma

Abstract

Objective:

This systematic review and meta-analysis was performed to study the potential of progression-free survival as a surrogate end point for trials evaluating the use of systemic therapy in advanced cervical cancer.

Methods: We performed a systematic review selecting phase II and III randomized trials including locally advanced, recurrent, and metastatic cervical cancer, with mature progression-free survival and overall survival data. Our study adhered to the Reporting Items for Systematic Reviews and Meta-Analyses checklist and was registered in International Prospective Register of Systematic Reviews (CRD42023405604). Exclusions comprised trials involving adjuvant treatment as the primary end point. The magnitude of progression-free survival and overall survival was assessed using standardized z-scores. Subgroup analyses were conducted based on treatment type, line of treatment, and prior radiotherapy exposure. Surrogacy was evaluated according to the recommendations by the Institut fir Qualit & auml;t und Wirtschaftlichkeit im Gesundheitswesen. Results: A total of 20 studies were included in the final analysis. In the overall population, a moderate correlation between progression-free survival and overall survival was observed (r = 0.75, p < .001). The surrogate threshold effect (STE) indicated a threshold for progression-free survival z-score (z-progression-free survival of 2.53), intersecting with null overall survival outcome (z = 1.96). Subgroup analysis revealed a weak and nonsignificant correlation in chemotherapy trials (r = 0.5, p = .12) with a higher STE (z-progression-free survival = 2.83). Conversely, chemoimmunotherapy combinations exhibited a robust and statistically significant correlation (r = 0.99, p = 0.01) with a lower STE (z-progression-free survival = 2.39). Trials exploring advanced therapy lines demonstrated a higher and more significant correlation (r=0.98,p=.02) with a lower STE at 2.08, whereas upfront-line therapy trials showed a moderate correlation(r=0.67,p=0.01) with an STE magnitude of 2.58. Conclusion: Progression-free survival exhibits a moderate correlation with a modest STE. For chemoimmunotherapy combinations, there is a strong correlation between overall survival and progression-free survival, with a notably lower STE. This suggests that the relationship between progression-free survival and overall survival may vary significantly based on the treatment strategy.