Page 220 - Read Online

Tang et al. Hepatoma Res 2019;5:19 I http://dx.doi.org/10.20517/2394-5079.2019.07 Page 5 of 9

Figure 3. Publication biases of included references

8.9%-34.4%), and pruritus 17.3% (95%CI: 13.5%-21.8%). The most common adverse event on grade greater
than 3 was increased AST, whose pooled estimated incident rate was 22.7% (95%CI: 13.8%-35.2%). The second
was increased ALT 13.9% (95%CI: 8.8%-21.3%). The remaining adverse events of grade greater than 3, such
as fatigue, pruritus, rash, diarrhoea, nausea, pulmonary toxicity, showed a small difference among pooled
estimated incident rates, which were around 1%-2%. The incident rate of Asthenia was only 0.9%, as shown
in Table 2.

DISCUSSION
This meta-analysis was performed to investigate the ORR published by paperswhich aimed to analyze the
effectiveness of ICIs in patients with HCC. The derived overall estimated ORR reported on these non-
heterogeneity papers is 19.8% (95%CI: 16.4%-23.7%, P < 0.001). The result of this study is different from the
investigation of other tumors. The difference maybe mainly caused by the heterogeneity among tumors.
High response rate (50%-90%) of ICIs can be obtained with classical Hodgkin lymphoma, desmoplastic
melanoma, Merkel cell carcinoma and microsatellite instability carcinoma. But the response rate of ICIs is
reduced to 15%-25% when treating solid tumors such as non-small cell lung cancer, head and neck cancer,
[22]
gastroesophageal cancer, bladder and urothelial cancer . Compared to hematological malignancies, HCC as
a solid tumor, shows not only a more complicated tumor microenvironment but the unique immune escape.
All of these reasons may cause the low ORR in HCC patients treated with ICIs. One of the effective ways to
[23]
enhance the drug response to ICIs is to obtain specific markers of liver cancer . A high rate of ORR (> 30%)
[24]
can be regard as a proper goal in the single arm clinical trial aiming at groundbreaking treatment . There
are currently five anti- PD-1/PD-L1 antibodies and two CTLA-4 blocking antibodies approved by the United
States Food and Drug Administration (FDA). But only Nivolumab and Tremelimumab were approved to
[25]
treat with HCC, with clinical trials of ICI agents currently ongoing . The overall estimated ORR is only
19.8% based on the current study, which needs to be verified with multicenter randomized controlled studies