Objective response rate and progression-free survival as surrogates for overall survival treatment effect: A meta-analysis across diverse tumour groups and contemporary therapies

• Published in: European journal of cancer (1990) 2024-02, Vol.198, p.113503-113503, Article 113503
• Main Authors: Shahnam, Adel, Hitchen, Nadia, Nindra, Udit, Manoharan, Sathya, Desai, Jayesh, Tran, Ben, Solomon, Benjamin, Luen, Stephen J., Hui, Rina, Hopkins, Ashley M., Sorich, Michael J.
• Format: Article
• Language: English
• Subjects: Objective response; Overall survival; Progression free survival; Surrogacy
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2023.113503

Overall survival (OS) results from randomized control trials (RCT) provide the strongest evidence for efficacy of anti-cancer treatments but can take a considerable amount of time to mature. Progression free survival (PFS) and objective response rate (ORR) are used as an early surrogate of OS treatment effect however their validity remains unclear. Our study aims to comprehensively evaluate ORR and PFS as surrogates for OS treatment effect across tumor groups and treatment types. Phase 3 RCTs in solid malignancies that reported OS/PFS and ORR published between 1st of January 2010 and 30th of June 2022 were evaluated. The relationship of surrogate endpoints and OS treatment effect was assessed via weighted linear regression. The coefficient of determination (R2) quantified the fit of the regression model. 675 phase 3 RCT comprising of 350 112 patients were analysed. ORR (R2 of 0.10) and PFS (R2 of 0.38) were poor surrogate markers of OS treatment effect. The strength of surrogacy differed within treatment and tumour groups. PFS had the highest R2 for chemotherapy (0.56) and lowest for targeted therapy (0.40). PFS had the highest level of surrogacy for melanoma (R2 = 0.72) and pancreatic cancer (R2 = 0.70) compared to other tumour groups. Importantly ORR and PFS were also poorly correlated to each other (R2 = 0.33). ORR and PFS were poor trial-level surrogate markers of OS. The surrogacy performance of ORR and PFS differed by treatment and malignancy sub-type. •ORR and PFS are not strong surrogates of OS treatment effect.•Surrogacy of ORR and PFS for OS differs based on treatment and tumor.•surrogacy of ORR and PFS for OS treatment effect was highest for chemotherapy.•PFS was a better surrogate of OS treatment for melanoma and pancreatic cancer.