PONE-D-24-04628Mirvetuximab Soravtansine in Solid Tumors: A Systematic Review and Meta-AnalysisPLOS ONE

Dear Dr. HongJing Wang,

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Journal Requirements:

Additional Editor Comments (if provided):

In this study, Shamsnur Rehim al. explored Mirvetuximab Soravtansine efficacy and safety in different cancers through a meta-analysis of different clinical studies. Their findings revealed that this ADC has significant therapeutic effects, especially when combined with Bevacizumab and in cancers expressing high levels of Folate Receptor ɑ. Although this study is of particular interest to the scientific community, the manuscript should be amended according to the reviewer’s concerns.

In addition to spell out words in full at first mention as requested by the reviewer (i.e., PRISMA, HR, RECIST, CTCAE, AE) FRɑ and rucaparib should be specified.

[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

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

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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

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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

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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 systematic review and meta-analysis by Rehim et al, provide a much needed analysis of the therapeutic benefits of MIRV based on several important variables including prior treatments, platinum response status, monotherapy and combination therapy, and FR-alpha expression levels, as well as adverse drug effects. This type of review is essential for identifying how all these variables affect therapeutic efficacy and safety and what research direction is needed to address outstanding therapeutic concerns. A major limitation of the current study is that many of the studies are not randomized controlled trials and the authors have duly acknowledged this limitation which is not of their own making. Nonetheless, the findings are very interesting. However, I do have several suggestions that will help improve the quality of the manuscript:

1. The data on prior lines of treatment is quite interesting but it would be helpful to further stratify the prior line of treatments based on the actual treatments the patients where receiving, their platinum response status, and their FR-alpha expression levels. This will help eliminate any potential confounding factors preventing us from seeing the importance of prior lines of treatment to the therapeutic effects of MIRV.

2. For table 1, the age should be provided as median IQR, and for the number of prior systemic treatments, what does the n mean? You provide a number and then another number in brackets. That is unclear.

3. It is important to spell out words in full at first mention and then continue using that abbreviation onwards. This is not addressed for PRISMA, HR, RECIST, CTCAE, AE.

4. There is definitely something wrong with the referencing method used in this paper, it is very inconsistent and unclear. The authors are advised to address this issue.

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Reviewer #1: No

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Mirvetuximab Soravtansine in Solid Tumors: A Systematic Review and Meta-Analysis

PONE-D-24-04628R1

Dear Dr. HongJing Wang,

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.

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Kind regards,

Cho-Hao Howard Lee, M.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: (No Response)

Reviewer #3: All comments have been addressed

Reviewer #4: All comments have been addressed

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2. 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: (No Response)

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: (No Response)

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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4. 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: (No Response)

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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5. 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: (No Response)

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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6. 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: (No Response)

Reviewer #2: Strengths:

Important Topic: I personally feel this study focuses on a very important and timely subject. Mirvetuximab Soravtansine (MIRV) is a novel treatment that has garnered attention recently, especially after its FDA approval. So, it's quite valuable to gather more comprehensive data about its efficacy and safety. The authors made a great choice in doing this systematic review and meta-analysis.

Extensive Literature Search: It’s really impressive how the authors combed through several reputable databases like PubMed and Cochrane. They didn’t leave any stones unturned when looking for studies. I think this strengthens the paper's reliability, especially since it includes a broad range of solid tumors.

Methodology is Sound: The authors followed the PRISMA guidelines, which I think adds to the strength of this work. They applied a random-effects model, which was quite appropriate, considering the heterogeneity. It shows that the team is aware of the technical demands of a meta-analysis.

Well-presented Results: The results were presented quite clearly. I especially liked the figures—particularly the forest plots—they made it easier to digest the data. It was well thought out, and I believe the readers will appreciate that too.

Clinical Relevance: The focus on the combination therapy of MIRV with Bevacizumab is quite useful, especially since platinum-resistant tumors are so hard to treat. The authors’ insights here seem practical for guiding future treatments.

Suggestions for Improvement:

High Heterogeneity: One thing I noticed right away is that the study suffers from quite high heterogeneity (I² values are up to 96%). It’s good that the authors used a random-effects model, but I personally feel they should dive a little deeper into why this heterogeneity exists. Maybe, they can discuss if doing more sensitivity analyses or meta-regressions could help.

Table Clarifications: Table 1 is quite confusing. The number of prior treatments needs better explanation, and even though the authors tried to explain in their response, it’s still a bit unclear to me. Maybe add more details in the legend to ensure readers get it right on the first glance.

Referencing Style Needs Attention: I think the referencing system could use some polish. It’s a little inconsistent throughout the manuscript, and I noticed that some citations don’t quite fit the style used elsewhere. The authors should ensure consistency for a better flow.

FRα Subgroup Analysis: The subgroup analysis on FRα expression is insightful, but honestly, there’s not enough data to support solid conclusions here. I’d recommend they mention the limitations more explicitly, so future researchers understand the gaps that still need to be filled.

Adverse Events: The discussion around adverse effects is good, but it could be better if they expanded a bit more on management strategies for common side effects, especially ocular toxicity. Given how prevalent it seems to be with MIRV, that would be a helpful addition.

Risk of Bias: I appreciate that the authors acknowledge the majority of studies included are single-arm trials, which obviously increases bias risk. But I feel they could discuss the influence of this bias in more detail. It would make the paper more robust in acknowledging its limitations.

Conclusion:

All in all, this is a solid paper that covers an important topic. I would personally recommend minor revisions, particularly around clarifying the tables and improving the discussion on heterogeneity and bias. Once these are addressed, I think it will be a valuable addition to the literature. It’s clear the authors have put in a lot of effort and attention to detail, so just a few tweaks are needed before this can be published.

Reviewer #3: The manuscript "Mirvetuximab Soravtansine in Solid Tumors: A Systematic Review and Meta-Analysis" is a high-quality work that provides valuable insights into the therapeutic potential of MIRV in solid tumors. I appreciate that the manuscript thoroughly addresses all previous comments. The authors have also ensured consistency in terminology and reference formatting, which meets the journal’s standards.

Given the thoroughness of the analysis and the overall quality of the manuscript, I see no need for further revisions. I commend the authors for their meticulous work and believe this manuscript makes a significant contribution to the literature on targeted therapies for solid tumors. I recommend it for publication as it stands.

Reviewer #4: I have reviewed the manuscript and I find it to be a well-executed and comprehensive meta-analysis that addresses an important area of research. The authors have systematically analyzed the efficacy and safety of Mirvetuximab Soravtansine in solid tumors, providing useful insights, particularly regarding the impact of different therapy regimens, platinum sensitivity, and FR-alpha expression levels. The manuscript is generally well-structured, with the results clearly presented and the discussion thoughtfully addressing the strengths and limitations of the study. The authors have made a commendable effort to stratify data and perform subgroup analyses, which adds depth to the findings. The statistical analysis are also sound.

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7. 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: Yes: Xiaoyi Zhang, MD

Reviewer #3: Yes: Yizhe Song

Reviewer #4: Yes: Yuhang Liu

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