Tumor response endpoints are “poor surrogate endpoints” for overall survival (OS) in trials of immune checkpoint inhibitors (ICIs), according to research published in JCO Precision Oncology.

Researchers conducted a systematic review and meta-analysis to determine whether objective response rate (ORR), complete response (CR) rate, and 6-month duration of response (DR) are acceptable surrogate markers for OS in trials of ICIs.

The team assessed correlations between the endpoints for treatment comparisons (trial-level analysis) and for patients receiving ICIs (arm-level analysis).

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The analysis encompassed 63 trials and 30,815 patients. Of the 78 ICI treatment arms, 58 were in randomized controlled trials, and 20 were in nonrandomized controlled trials.

The trials were published between Jan. 1, 2000, and March 31, 2020. Most (63%) were phase 3 trials, and OS was the most common primary endpoint (40%). Cancer types included lung, skin, gastrointestinal, genitourinary, head and neck, breast, and neuroendocrine.

In the trial-level analysis, ORR, 6-month DR, and CR were not strongly correlated with OS. The correlation coefficient (r value) was 0.58 for the relationship between the ORR risk ratio and the OS hazard ratio (HR), 0.62 for the 6-month DR ratio vs OS HR, and 0.42 for the CR risk ratio vs OS HR.

In the arm-level analysis, ORR and 6-month DR — but not CR — were prognostic for 12-month OS. The correlation coefficient was 0.76 for ORR vs 12-month OS, 0.84 for 6-month DR vs 12-month OS, and 0.50 for CR vs 12-month OS.

“In conclusion, tumor response endpoints, which include ORR, 6-month DR, and CR, are poor surrogate endpoints for OS in immunotherapy trials, and OS remains the most important and clinically meaningful endpoint,” the researchers wrote. “However, ORR and 6-month DR are prognostic for 12-month OS. This supports their use in drug development and screening of agents for phase 3 studies.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures. 


Kok P-S, Yoon W-H, Lord S, Marschner I, Friedlander M, Lee CK. Tumor response end points as surrogates for overall survival in immune checkpoint inhibitor trials: A systematic review and meta-analysis. JCO Precis Oncol. 2021;5:1151-1159. doi:10.1200/PO.21.00108