Identifying optimal first-line immune checkpoint inhibitors based regiments for advanced non-small cell lung cancer without oncogenic driver mutations: A systematic review and network meta-analysis

Tingting Liu; Sijia Wu; Weiwei Fang; Hongkai Li; Lili Su; Guiye Qi; Huaichen Li; Yao Liu

doi:10.1371/journal.pone.0283719

Peer Review History

Original SubmissionSeptember 24, 2022
24 Jan 2023 Decision Letter - Rama Krishna Kancha, Editor PONE-D-22-24716Identifying optimal first-line immune checkpoint inhibitors based regiment s for advanced non-small cell lung cancer without oncogenic drivers: a systematic review and network meta-analysisPLOS ONE Dear Dr. Liu, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Mar 10 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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Additional Editor Comments: The reviewers opined that the study is valuable except for few suggestions that include (1) the importance of this study is overstated saying that it influences the decision regarding first-line treatment and (2) concerns regarding certain parameters used in this study. Please address reviewers' concerns point-wise in the rebuttal. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: I Don't Know ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: No ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: The manuscript's topic if of great interest and relevance. Also the aim and outcomes are well described. The methodogy is correct. The presentation of the results is exhaustive and clear. I have just few minor comments that require revisions: Comments: 1) In the conclusion of the abstract and of the full text, the authors state that their findings may guide the choice of the first-line treatment of NSCLC. In my opinion, even if comprehensive and weel-designed, a meta-analysis cannot directly led to prefer a treatment over another. It can suggest or give basis for a clinical-based evidence therapeutic decision. Please changes the terms of this sentence both in the abstract as well as in the conclusions. 2) at the end of page 9 when presenting the aim of the study ".to determine the optimal first-line immunotherapies ......", I would prefer the use of the following terms "to compare the different first-lines regimens in term of efficacy" (please ad the parameters chosen for comparison). Reviewer #2: Immune checkpoint inhibitors (ICIs) have greatly changed the treatment pattern of advanced and metastatic NSCLC. In recent years, the results of a number of prospective studies evaluating the efficacy and safety of immunochemotherapy in the first-line treatment of advanced NSCLC have been published. The authors undertook the task of summarising the results of these studies in the form of a network meta-analysis with the aim of determining the optimal first-line immunotherapies for advanced NSCLC. The topic addressed is important from a practical point of view. However, I have a few comments. 1. In the discussion, the authors highlight the limitations of the manuscript - for example, related to the ethnic diversity of the populations eligible for treatment or the diagnostic issues of PD-L1. They also highlight the lack of studies directly comparing different immunochemotherapy regimens. However, it will be worth much more emphasizing the limited value of indirect comparisons of results obtained by patients treated across multiple different regimens, with varying follow-up times and different population sizes. 2. The authors conclude that the results of the present NMA may assist the initial choice of first-line immunotherapies for advanced NSCLC patients. In my opinion, one should be tempted to provide further clarification, a summary, and a proposed treatment algorithm included in the table. Specifying the following subpopulations: PD-L1 <1%, 1-49%, >50% in each histological type (squamous vs non-squamous). 3. In the 'data extraction' section, it is stated that among the variables collected were the age and gender of the patients. Were analyses of the prognostic value of these parameters performed? 4. My additional suggestion is to add the word „mutations“ in the title and further parts of the manuscript (oncogenic driver mutations). Furthermore, it is worth noting, that the paper only refers to abnormalities in the EGFR and ALK genes. Therefore, maybe consider specifying in the title which molecular abnormalities are referring to. 5. Furthermore- please note that numerous items of the references need to be corrected. ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: No ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0283719.r001
Revision 1
13 Mar 2023 Author Response Dear editors Thanks you very much for your comments and suggestions. We have revised the manuscript, according to the comments and suggestions of reviewers and editor, and responded, point by point to, the comments as listed below. We have highlighted all the changes in red. I would like to re-submit this revised manuscript to Plos One, and hope it is acceptable for publication in the journal. Looking forward to hearing from you soon. With kindest regards, Yours Sincerely Yao Liu Replies to Reviewers and Editor First of all, we thank both reviewers and editor for their positive and constructive comments and suggestions. Reviewer #1: The manuscript's topic if of great interest and relevance. Also the aim and outcomes are well described. The methodogy is correct. The presentation of the results is exhaustive and clear. I have just few minor comments that require revisions: Comments: 1) In the conclusion of the abstract and of the full text, the authors state that their findings may guide the choice of the first-line treatment of NSCLC. In my opinion, even if comprehensive and weel-designed, a meta-analysis cannot directly led to prefer a treatment over another. It can suggest or give basis for a clinical-based evidence therapeutic decision. Please changes the terms of this sentence both in the abstract as well as in the conclusions. Answer: This is a very constructive suggestion. We have rewritten these sentences both in the abstract as well as in the conclusions. 2) at the end of page 9 when presenting the aim of the study ".to determine the optimal first-line immunotherapies ......", I would prefer the use of the following terms "to compare the different first-lines regimens in term of efficacy" (please ad the parameters chosen for comparison). Answer: Thank you for the suggestion. We have rewritten this sentence in the paragraph above the Methods section. Reviewer #2: Immune checkpoint inhibitors (ICIs) have greatly changed the treatment pattern of advanced and metastatic NSCLC. In recent years, the results of a number of prospective studies evaluating the efficacy and safety of immunochemotherapy in the first-line treatment of advanced NSCLC have been published. The authors undertook the task of summarising the results of these studies in the form of a network meta-analysis with the aim of determining the optimal first-line immunotherapies for advanced NSCLC. The topic addressed is important from a practical point of view. However, I have a few comments. 1. In the discussion, the authors highlight the limitations of the manuscript - for example, related to the ethnic diversity of the populations eligible for treatment or the diagnostic issues of PD-L1. They also highlight the lack of studies directly comparing different immunochemotherapy regimens. However, it will be worth much more emphasizing the limited value of indirect comparisons of results obtained by patients treated across multiple different regimens, with varying follow-up times and different population sizes. Answer: Thank you for the constructive suggestion. We have added the limited value of indirect comparisons of results in the discussion. 2. The authors conclude that the results of the present NMA may assist the initial choice of first-line immunotherapies for advanced NSCLC patients. In my opinion, one should be tempted to provide further clarification, a summary, and a proposed treatment algorithm included in the table. Specifying the following subpopulations: PD-L1 <1%, 1-49%, >50% in each histological type (squamous vs non-squamous). Answer: Thank you for the constructive suggestions. We have added a table (Table 2) in the revised manuscript, which further summarize the optimal treatment regimens for NSCLC according to PD-L1 expression level and different pathological types. 3. In the 'data extraction' section, it is stated that among the variables collected were the age and gender of the patients. Were analyses of the prognostic value of these parameters performed? Answer: We regret that we were unable to conduct additional analyses of the prognostic value of these parameters. 4. My additional suggestion is to add the word “mutations” in the title and further parts of the manuscript (oncogenic driver mutations). Furthermore, it is worth noting, that the paper only refers to abnormalities in the EGFR and ALK genes. Therefore, maybe consider specifying in the title which molecular abnormalities are referring to. Answer: Thank you for the suggestion. We have added the word “mutations” in the title and further parts of the manuscript. 5. Furthermore- please note that numerous items of the references need to be corrected. Answer: We are very sorry for these mistakes. We have corrected the references (ref 4, ref 14, ref 21, ref 36 and ref 41) in the Reference section of the revised manuscript. In addition, some data were extracted from the contents of the major conferences and have not been published as articles, for which we may not modify these references. Furthermore, we revised the manuscript according to the Journal Requirements section. The changes as listed below. 1. We have added the Role of Funder statement section and include this amended section in our manuscript and cover letter. 2. We have rectified the Data Availability Statement section. The relevant data are within the supporting files. 3. We have moved ethics statement to the Methods section. 4.We have modified the position of figures and tables in our text. 5. According to the comments, we have inserted the tables into the manuscript. 6. Tingting Liu, Sijia Wu, and Weiwei Fang should be considered co-first authors. We are very sorry for this mistake, and we have rectified that section in our manuscript. Attachments Attachment Submitted filename: Response to Reviewers.doc https://doi.org/10.1371/journal.pone.0283719.r002
15 Mar 2023 Decision Letter - Rama Krishna Kancha, Editor Identifying optimal first-line immune checkpoint inhibitors based regiments for advanced non-small cell lung cancer without oncogenic driver mutations: a systematic review and network meta-analysis PONE-D-22-24716R1 Dear Dr. Liu, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Rama Krishna Kancha Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0283719.r003
Formally Accepted
3 Apr 2023 Acceptance Letter - Rama Krishna Kancha, Editor PONE-D-22-24716R1 Identifying optimal first-line immune checkpoint inhibitors based regiments for advanced non-small cell lung cancer without oncogenic driver mutations: a systematic review and network meta-analysis Dear Dr. Liu: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Rama Krishna Kancha Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0283719.r004

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