REFLECT study is the first phase III clinical study in to obtain positive results in the first-line treatment of advanced HCC in ten years since the launch of sorafenib . With this research result, lenvatinib has become a first-line treatment option for advanced HCC. To continue to explore the precise treatment of HCC, research on the prognosis prediction of lenvatinib in patients with advanced HCC is continuing. Whether objective response (objective response) is a major indicator for evaluating the efficacy of cancer patients with anti-tumor treatment, and whether it can be used as an independent predictor of prognostic survival in HCC patients still needs further verification.
In order to comprehensively analyze the relationship between HCC patients' objective response to lenvatinib and the overall survival (OS) in the REFLECT study, Professor Masatoshi Kudo, an affiliated hospital of the Kinki University School of Medicine, Japan, recently published a latest research result in the journal JOH.
article published a cover image (Source: https://www.journal-of-hepatology.eu)
It is well known that for tumor patients, objective response is the main tool for evaluating the efficacy of radiotherapy, chemotherapy, targeted therapy and immunotherapy . Based on different anti-tumor treatment methods, the evaluation criteria for our evaluation of their efficacy are also different, such as: traditional (such as chemotherapy and targeted therapy) solid tumor efficacy evaluation criteria (RECISTv1.1) and improved solid tumor efficacy evaluation criteria (mRECIST); with the great progress of immunotherapy, the efficacy evaluation criteria for solid tumor immunotherapy (immune-modified Response Evaluation Criteria In SolidTumors, ImRECIST) have emerged.
REFLECT study is a global, randomized, open-label, phase III clinical study that evaluates the efficacy of lenvatinib in patients with sorafenib in first-line treatment of unresectable hepatocellular carcinoma (uHCC). In earlier study analysis, lenvatinib showed non-inferiority to sorafenib, with the overall survival (OS) of the two being 13.6 months (95%CI: 12.1-14.9) vs. 12.3 months (95%CI: 10.4-13.9) (HR=0.92, 95%CI: 0.79-1.06). In addition, lenvatinib can significantly prolong progression-free survival compared with sorafenib (PFS), at 7.4 months (95%CI: 6.9-8.8) vs. 3.7 months (95%CI: 3.6-4.6) respectively. The objective response rate (ORR) of the two was 24.1% (95%CI: 20.2-27.9) vs. 9.2% (95%CI: 6.6-11.8) respectively.
In the latest study, Professor Kudo et al. collected objective responses based on mRECIST evaluation from the researcher's perspective and objective responses based on mRECIST and RECIST1.1 from the perspective of independent radiological review, and analyzed their relationship with OS.
Article related image summary (DOI: https://doi.org/10.1016/j.jhep.2022.09.006) The final study results of
showed that the median OS for responders (researchers evaluated mRECIST) was 21.6 months (95%CI: 8.6 to 24.5), and those without responders were 11.9 months (95%CI: 10.7 to 12.8) (HR=0.61, 95%CI: 0.49 to 0.76; P0.001).
Objective responses based on mRECIST and RECIST1.1 from the perspective of independent radiology review also showed correlation with OS (HR=0.61, 95%CI: 0.51~0.72, P0.001 and HR=0.50, 95%CI: 0.39～0.65, P0.001). The evaluation of independent radiology review showed that the objective responses based on mRECIST and RECISTv1.1 were similar.
further exploratory multi-factor Cox regression analysis showed that the objective response based on mRECIST researchers' evaluation (HR=0.55, 95%CI: 0.44-0.68, P0.001) and the objective response based on RECISTv1.1 independent radiographic review evaluation (HR: 0.49, 95%CI 0.38-0.64, P0.0001) can all be used as independent predictors of OS in HCC patients.
In summary, this study analyzed the complete data of the REFLECT study and the results showed that the objective response of lenvatinib in the treatment of advanced HCC is an independent predictor of OS in HCC patients. Patients who achieved complete or partial remission through mRECIST or RECISTv1.1 had significantly longer survival compared with patients with stable or progressive and non-responsive conditions.
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