OBJECTIVES: Recent publications did not find strong evidence to support the surrogacy of progression-free survival (PFS) for overall survival (OS) in patients with ovarian cancer patients undergoing first-line platinum-based therapy. The surrogacy analysis could be confounded by multiple factors, including post-relapse treatments. To investigate this topic further we assessed whether PFS may be a surrogate for OS in patients with platinum-resistant/refractory ovarian cancer (PROC).

METHODS: A systematic literature review (SLR) of randomized clinical trials in PROC published between 2010 and April 2022. Cytel’s LiveSLR™ platform was used to select and analyze the results in line with NICE and Cochrane guidance. Trials reporting PFS and OS were used in a surrogate endpoint validation in alignment with IQWiG guidelines.

RESULTS: Twenty-nine two-arm RCTs that reported the hazard ratio for both OS and PFS were identified. The estimated overall treatment effect on the surrogate was 0.13 (80% CI: 0.05 – 0.21). The correlation (R) between PFS and OS was 0.68 (p<0.001), with a surrogate threshold effect of 0.11. According to IQWiG guidelines, a strong correlation is indicated by R≥0.85. An effect on the patient-relevant endpoint may exist when the 80% CI of the effect on the surrogate is larger than the surrogate threshold effect. In this case, the correlation was moderate but statistically significant. The lower bound of the 80% CI (and 95% CI) of the effect on the surrogate was smaller than the surrogate threshold effect, providing no evidence for PFS as a surrogate for OS. Similar results were observed in a subgroup analysis of platinum-resistant ovarian cancer.

CONCLUSIONS: There was insufficient evidence to support PFS as a surrogate for OS in PROC. However, the analysis may have been confounded by the effect of additional treatments following relapse. Further analyses will explore other surrogates like objective response rate and other subgroups.