First- and Second-Line Treatments for Patients with Advanced Hepatocellular Carcinoma in China: A Systematic Review
Round 1
Reviewer 1 Report
The authors have summarized the use of first line systemic therapy in HCC focused on Chinese patients. The authors conclude that atezolizumab or sintilimab plus bevacizumab or a biosimilar are the best first line therapeutic intervention in HCC. Authors also point out that TKI and oxaliplatin-based chemo therapy may be advantageous but should be carefully reviewed in the context of patients before proceeding. The second line treatments are not so correctly in place as yet and are less efficient.
The study investigates only 30 articles (narrowed down to include all the criteria) to make these conclusion. I would recommend increasing the number of articles to support the conclusions.
Author Response
Response: We thank the reviewer for this comment. There were several reasons for not including a greater number of articles in this review, some of which are mentioned in the original text. Firstly, as this was a systematic review and not a meta-analysis, the data were not synthesised, and we instead selected the articles with the strongest/most robust evidence for each therapy type, as described in the methods section. If a larger number of studies were included we feel the review would become unmanageable. Secondly, the vast majority of studies identified (particularly Chinese-language studies) were small, single arm, single centre studies, and we did not consider it robust or meaningful to include a large number of this type of study and attempt to summarise the data from them.
Reviewer 2 Report
Interesting concept for a review of HCC treatment evidence in Chinese patients which account for a significant proportion of HCC in the world. Publication in an English language journal would provide some insight for oncologists outside of China regarding how this disease is treated in China. Comprehensive review which summarizes the current evidence in an organized way.
A few questions:
1. Why did the authors only include ASCO and ESMO abstract searches for 1 year of meetings? Why not include ASCO 2019, ASCO GI 2020, ESMO 2019 and ESMO GI 2019?
2. It is stated in the Methods: Data Collection and Data Items that "Any disagreements were resolved by discussion and assistant from a third party". Please specify who this third-party was, was it another one of the authors? It may be reasonable to include the initials of the two reviewers and third-party if they are all authors on this manuscript.
3. In figure 1 it is not clear at the bottom of the figure. 156 reports assessed for eligibility and then 131 excluded, leaving 25 reports. How is it that 28 "studies" are included and then 30 "reports of studies" are included? Were there 2 studies with multiple reports? Also in the footnote the authors state that 5 studies were added during writing of the review. It is not clear where did these 5 additional studies come from and whether there was a systematic process to identify and include them.
4. In Table 6 it would be helpful if the column headings are repeated for each category (TKI, PD-1/PD-L1 inhibitor, chemotherapy, etc.) Since this table is very large when you read it further down it is hard to see which values align with ORR, Median PFS, Median OS, etc. Also consider sorting the results by intervention (e.g. so that all the apatinib trials are together).
5. Also for Table 6 consider adding a column for "Line of treatment" to indicate 1st- or 2nd-line systemic therapy as this can affect outcomes.
6. In the discussion, the results of IMbrave150 are discussed around line 422. There is an updated analysis in Journal of Hepatology 2022. The authors should consider using the updated efficacy results.
Author Response
- Why did the authors only include ASCO and ESMO abstract searches for 1 year of meetings? Why not include ASCO 2019, ASCO GI 2020, ESMO 2019 and ESMO GI 2019?
Response: We thank the reviewer for this question. We selected only one year of meetings as we assumed important/impactful studies would have been published in full. As meeting abstracts are not fully peer reviewed, we preferred to include full peer-reviewed studies where possible.
- It is stated in the Methods: Data Collection and Data Items that "Any disagreements were resolved by discussion and assistant from a third party". Please specify who this third-party was, was it another one of the authors? It may be reasonable to include the initials of the two reviewers and third-party if they are all authors on this manuscript.
Response: The third party was Jake Burrell PhD, who is acknowledged as a medical writer. The reviewers were the authors of the paper.
- In figure 1 it is not clear at the bottom of the figure. 156 reports assessed for eligibility and then 131 excluded, leaving 25 reports. How is it that 28 "studies" are included and then 30 "reports of studies" are included? Were there 2 studies with multiple reports? Also in the footnote the authors state that 5 studies were added during writing of the review. It is not clear where did these 5 additional studies come from and whether there was a systematic process to identify and include them.
Response: Thank you for this careful feedback. For the total number of reports added, the exclusion criteria are not mutually exclusive, and some studies were excluded for more than one reason. We have added a new footnote to explain/clarify this. There were 28 studies and 30 reports because two studies included had a primary publication and an updated publication, both of which were included. The 5 additional studies were added either because they were published after the date of the initial literature search or because they were excluded based on the title and abstract and then later considered for inclusion based on the author’s knowledge of the content. We have clarified these points in the revised figure legend.
- In Table 6 it would be helpful if the column headings are repeated for each category (TKI, PD-1/PD-L1 inhibitor, chemotherapy, etc.) Since this table is very large when you read it further down it is hard to see which values align with ORR, Median PFS, Median OS, etc. Also consider sorting the results by intervention (e.g. so that all the apatinib trials are together).
Response: Thank you for this suggestion. We have added the column headings to each category as requested and also grouped the results by intervention.
- Also for Table 6 consider adding a column for "Line of treatment" to indicate 1st- or 2nd-line systemic therapy as this can affect outcomes.
Response: We have added line of treatment where this information was available in the articles.
- In the discussion, the results of IMbrave150 are discussed around line 422. There is an updated analysis in Journal of Hepatology 2022. The authors should consider using the updated efficacy results.
Response: Thank you for this suggestion. We have updated the data and added the new reference.
