Current and Emerging Role of Monoclonal Antibody-Based First-Line Treatment in Advanced Gastro-Esophageal and Gastric Cancer

Round 1

Reviewer 1 Report

The manuscript is a review discussing the role of monoclonal antibodies in treating advanced adenocarcinomas of the stomach and gastro-esophageal junction, focusing on first-line treatments.

Major Comments:

1. Lack of Details on Literature Search Methodology: The manuscript does not elucidate the methodology employed for the literature search. No information is provided on the databases consulted, the search terms used, the time frame considered, and the criteria for including or excluding literature. A section detailing the literature search strategy should be included, specifying the databases searched (e.g., PubMed, Scopus), the search terms used, and any inclusion or exclusion criteria applied to select the studies. This would enhance the transparency and reproducibility of the literature search and allow readers to assess the comprehensiveness and quality of the literature included in the review.
2. Inconsistency in Referencing: The manuscript seems inconsistent in the text's presentation of references. While some statements are directly cited, others lack immediate reference, leading to ambiguity regarding the source of the information. Example & Suggestion: Standardizing how references are integrated within the text is crucial. Every statement or claim made in the manuscript should be appropriately and consistently referenced, enhancing the manuscript's clarity and credibility and allowing readers to easily trace the source of the information.
3. Clarity and Cohesiveness: The manuscript is detailed but could benefit from a more structured and cohesive presentation of the information. For example, the transitions between discussions on monoclonal antibodies could be smoother. Example: Before transitioning from discussing anti-HER2 receptor to anti-VEGF, a summarizing statement or a transitional sentence would help maintain the manuscript's flow and coherence.
4. Depth of Information: While the manuscript is rich, it could delve deeper into the mechanisms of action of the discussed antibodies and their implications. Example: The section on Anti-HER2 could benefit from more detailed information on how HER2 overexpression leads to aberrant cellular growth and proliferation in gastric cancers.
5. Consistency in Presentation of Clinical Trials: The presentation of clinical trials and their results is somewhat inconsistent. Standardizing the presentation of trial results would aid in comprehension. Example: The results of the ToGA trial and the JACOB trial are presented differently. Standardizing the presentation, such as first stating the trial's aim, followed by methodology, results, and implications, would be helpful.
6. In-depth Discussion on Negative Results: The manuscript mentions negative results from certain trials but does not discuss the implications or reasons behind these results. Example: The manuscript mentions the negative results of the RAINFALL trial but does not discuss why the addition of ramucirumab showed negative results or the implications of these negative results.

Minor Comments:

1. Use of Technical Jargon:
• The manuscript is heavy on technical terms and jargon, which might make it less accessible to readers not well-versed in oncology or immunotherapy.
• Example: The manuscript could benefit from briefly explaining or defining terms such as “microsatellite unstable tumors” and “PD-L1 CPS score.”
2. References and Citations:
• Some statements and claims in the manuscript lack proper references or citations.
• Example: The statement “PD-L1 expression is reported in about 40% of patients with gastroesophageal adenocarcinomas” could benefit from a relevant study or source citation.
3. Visual Aids:
• The inclusion of more visual aids like tables, graphs, or flowcharts summarizing the discussed antibodies, their targets, and trial results would enhance understanding.
• Example: A table summarizing the different antibodies discussed, their targets, and a summary of trial results would be helpful.
4. Conclusion Section:
• A more comprehensive conclusion summarizing the main points, findings, and implications of the discussed antibodies would be beneficial.
• Example: A conclusion succinctly summarizes the main findings from the discussed trials, and the implications of these findings on the treatment landscape of gastric cancers would round off the manuscript well.

 

 

1. Based on the provided excerpts from the document, the quality of English language appears to be generally good, with clear and coherent sentences. However, here are some comments and suggestions to further enhance the clarity and readability of the paper:
2.  

3. Clarity and Conciseness:

   • Some sentences are quite lengthy and could benefit from being broken down into shorter, more concise sentences to improve readability and understanding. Example: “Monoclonal antibodies are now widely used in the treatment of advanced adenocarcinomas of the stomach and gastro-esophageal junction in the first line setting.” could be broken down for clarity, e.g., “In the first-line setting, monoclonal antibodies have become a prevalent treatment for advanced adenocarcinomas of the stomach and gastro-esophageal junction.”

4. Consistency in Terminology:

   • Consistency in the use of terms and abbreviations is crucial. If abbreviations are used, they should be clearly defined at their first occurrence, and the same term or abbreviation should be used consistently throughout the document. Example: The document refers to “PD-L1 expression” and uses terms like “CPS” and “ICI.” Ensure that such terms and abbreviations are consistently used and clearly defined when first introduced.

5. Punctuation and Formatting:

   • Attention to proper punctuation and formatting is essential for maintaining the flow and readability of the text. Example: Ensure proper use of commas, periods, and other punctuation marks, and maintain consistent formatting for headings, subheadings, and text throughout the document.

6. Reference Integration:

   • The integration of references within the text should be clear and consistent, allowing readers to easily trace the source of the information.
   • Example: Standardize the way references are integrated within the text and ensure that all statements and claims made in the document are appropriately and consistently referenced.

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Reviewer 2 Report

The article entitled “Current and Emerging Rple of Monoclonal Antibody-Based First Line Treatment in Advanced Gastro-esophageal and Gastric Cancer” by Audrey Desilets, et al. demonstrated that the impact of monoclonal antibodies targeting PD-1/PD-L1, VEGF, HER2, and CLDN18.2 on the treatment landscape.

This study has some value, however, the mention about the impact of each monoclonal antibodies is slightly thin. As a result, the authors present a limited interest. 

Thus, there are areas that need to be improved.

Major comments

1.    Authors describe too much about PD-L1 expression. These should be revised. Furthermore, authors should provide the mention about MSI, dMMR, TMB as promising predictive biomarker of anti-PD-/PD-L1 antibodies. 

2.    Descriptions about “Anti-VEGF”, the relationship between Anti-VEGF antibody and Anti-PD-1/PD-L1 antibody.

3.    There is not enough mention about Antibody-drug conjugates, such as trastuzumab-deruxtecan that can yield reliable improvement of outcome in patients with HRE2 positive gastric cancer.

Minor comments

1.    Authors should change the order of descriptions regarding monoclonal antibodies.

(1)Anti-PD-1/PD-L1, (2)Anti-VEGF, (3)Anti-HER2 receptor, (4)Anti-Claudin 18.2

2.    Descriptions in the “Abstract” (line 11-16) and “Introduction” (line 32-40) are somewhat redundant and need shortening considerably.

3.    Descriptions about negative results in the part of “Anti-VEGF” are somewhat redundant and need shortening considerably.

4.    Descriptions about adverse events of monoclonal antibody that targets CLDN18.2 are somewhat redundant and need shortening considerably.

Minor editing of English language required.

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

I am pleased to note that all my concerns and comments have been thoroughly addressed. I believe the manuscript is now in a polished state and recommend it for publication.

 

Author Response

We thank you for your comments and are very pleased that you recommend our manuscript for publication.

 

Sincerely,

Audrey Désilets, M.D.,

Oncology Resident

Reviewer 2 Report

The article entitled “Current and Emerging Rple of Monoclonal Antibody-Based First Line Treatment in Advanced Gastro-esophageal and Gastric Cancer” by Audrey Desilets, et al. demonstrated that the impact of monoclonal antibodies targeting PD-1/PD-L1, VEGF, HER2, and CLDN18.2 on the treatment landscape.

Authors response to reviewer’s comments is generally appropriate.

There are some areas that need to be improved.

Major comments

1.    In Descriptions about “Anti-VEGF”, there is no meaningful mention about the relationship between Anti-VEGF antibody and Anti-PD-1/PD-L1 antibody.

Kato K, et al. have reported efficacy analysis of Nivolumab in patients with prior ramcirumab treatment (Kato K, et al. Gastric Cancer. 2019.22(2):344-354.). Furthermore, the combination of atezolizumab and bevacizumab showed encouraging antitumor activity in clinical trial involving patients with unresectable hepatocellular carcinoma (N Engl J Med. 2020 May 14;382(20):1894-1905.).

Authors should describe about the necessity to verify the effectiveness of combination of anti-VEGF and anti-PD-1/PD-L1 to a standard treatment in first line treatment in advanced GEJ and GC.

 

Minor comments

1.    Descriptions in the “Introduction” (line 32-40) are somewhat redundant and need shortening considerably.

 

Author Response

Please see attachment. 

Author Response File: Author Response.docx

Round 3

Reviewer 2 Report

The author's response to the reviewer's comments was adequate, and the revised manuscript was appropriately refined. As a result, this report is of great interest.