Predictive value of radiological response, pathological response and relapse-free survival for overall survival in neoadjuvant immunotherapy trials: pooled analysis of 29 clinical trials

Runcong Nie, Foping Chen, Mariano Provencio, Yun Wang, Tom van den Ende, Hanneke W. M. van Laarhoven, Shuqiang Yuan, Miklos Pless, Stefanie Hayoz, Zhiwei Zhou, Yuanfang Li, Sacha I. Rothschild, Muyan Cai

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Scopus)


Background: An increasing number of clinical trials are being conducted exploring the efficacy of neoadjuvant immune checkpoint inhibitors. Surrogate end-points for overall survival (OS) are urgently needed. Methods: Phase II or III trials of neoadjuvant immunotherapy that reported data on OS and surrogate end-points were identified from January 1, 2000, to November 25, 2022. Individual patient data, and trial-level data were requested from corresponding authors or extracted from eligible trials. At the individual level, correlations between radiological and pathological response and OS were measured by the Cox model and quantified by hazard ratio (HR). C-statistic was used to quantify the predictive performance of radiological and pathological response for OS. The coefficient of determination (R2) between RFS and OS was evaluated by a bivariate survival model. Results: A total of 29 trials reporting 2901 patients were included. ORR correlated with improved OS (3-year OS: 87.0% versus 70.4% for ORR versus non-ORR, respectively; HR, 0.34, 95% confidence interval [CI], 0.17–0.68). The HRs for OS in patients achieving MPR and pCR were 0.24 (95% CI, 0.12–0.46) and 0.13 (95% CI, 0.05–0.36). The survival benefit maintained after adjusting tumour type. C-statistics of ORR, MPR and pCR were 0.63, 0.63 and 0.65, respectively. The strength of association between RFS and OS was strong (R2 = 0.88, 95% CI, 0.79–0.94). Conclusions: These findings suggest that ORR, MPR, pCR and RFS are valid predictors for OS when using neoadjuvant immune checkpoint inhibitors. Moreover, MPR, pCR and RFS may be the most optimal surrogates for OS.
Original languageEnglish
Pages (from-to)211-221
Number of pages11
JournalEuropean Journal of Cancer
Early online date2023
Publication statusPublished - Jun 2023


  • End-point
  • Immunotherapy
  • Neoadjuvant
  • Overall survival
  • Surrogate

Cite this