{'fraction_non_alphanumeric': 0.03686366296079579, 'fraction_numerical': 0.025746050321825628, 'mean_word_length': 4.738255033557047, 'pattern_counts': {'":': 0, '<': 1, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Objective Response Predicts Survival in Advanced Hepatocellular Carcinoma treated with Systemic Therapies.

PURPOSE
Due to the increased number of sequential treatments used for advanced HCC, there is a need for surrogate endpoints of overall survival (OS). We analyze if objective response (OR) is an independent predictor and surrogate endpoint of OS.


EXPERIMENTAL DESIGN
A systematic review of randomized clinical trials (RCTs) in advanced HCC published between 2010 and 2020 was conducted to explore OS surrogacy of OR by RECIST and mRECIST. In parallel, RCTs exploring the impact of OR on OS in a time-dependent multivariate analysis were integrated in a meta-analysis.


RESULTS
Out of 65 RCTs identified in advanced HCC, we analyzed 34 studies including 14,056 patients that reported OS and OR by either RECIST (n=23), mRECIST (n=5) or both (n=6). When exploring surrogacy, the trial-level correlation between OR odds ratio and OS hazard ratio was R=0.677 by mRECIST and R=0.532 by RECIST. Meta-analysis of five RCT assessing predictors of survival in multivariate analysis found that patients with OR by mRECIST presented a pooled HR for OS of 0.44 (95% CI, 0.27-0.70, p<0.001) compared with non-responders. Responses to atezolizumab-bevacizumab had a greater impact on OS than tyrosine-kinase inhibitor responses.


CONCLUSIONS
OR-mRECIST is an independent predictor of OS in patients with advanced HCC. Although correlation of OR-mRECIST and OS is better than with OR-RECIST, the level of surrogacy is modest. Thus, it can be used as endpoint in proof-of-concept phase II trials, but the data does not support its use as a primary endpoint of phase III investigations assessing systemic therapies.