PONE-D-23-26174Impact ofPARP inhibitor maintenance therapy in newly diagnosed advanced epithelial ovarian cancer: A meta-analysisPLOS ONE

Dear Dr. Chang,

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.

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Academic Editor

PLOS ONE

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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: Partly

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

Reviewer #1: Yes

Reviewer #2: No

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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

Reviewer #2: 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

Reviewer #2: No

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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 manuscript entitled “Impact ofPARP inhibitor maintenance therapy in newly diagnosed advanced epithelial ovarian cancer: A meta-analysis” by Lee et al. presents a comprehensive metaanalysis of studies investigating the effects of PARPi maintenance therapy in advanced EOC. The paper provides insights into the effect of PARPi therapy in advanced. There are a couple of points need to be addressed:

My major critique is that the study did not use a systematic review protocol, which may potentially introduce bias and affect the overall reliability of the results. This has been acknowledged in the paper, however, the reason behind it was not clarified. Another major limitation is the limited studies included for the meta-analysis.

In addition, there are a couple of minor points to consider:

1. Better to label the subgroups in each panel of Fig2 and Fig3.

2. It would be good to include a brief explanation of the I2 statistic and Cochran's Q statistics used to assess the heterogeneities as they are not common tests.

Reviewer #2: Chang et al. conducted a systematic review and meta-analysis on “Impact of PARP inhibitor maintenance therapy in newly diagnosed advanced epithelial ovarian cancer (EOC)”. They eventually inferred that in newly diagnosed advanced EOC patients, PARPi maintenance therapy was significantly more effective in terms of survival compared to placebo group. However, there are major issues without addressing which the manuscript will not go to publication in PLOS ONE. Below are point-by-point comments and concerns that warrant clarity and/or corrections.

Abstract:

Title: Please put a space after “of”

Objectives:

Please keep the statement as below, because evaluation of adverse effects was not the main aim of this study.

“This meta-analysis was undertaken to systematically evaluate the effects of poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance therapy on survival of newly diagnosed advanced epithelial ovarian cancer (EOC) patients.”

Methods:

Please include the software used for statistical analysis as this study is a meta-analysis.

Results:

Hazard ratio [HR] for disease progression or death, and confidence interval [CI] to be initially written in full and abbreviations can be applied thereafter.

Introduction:

1. Overall the introduction is shallow and authors are recommended to clearly mention key concepts of the study, figure out why the topic is important, provide literature review related to this topic, identify existing gaps and finally define the aim of the study.

2. In lines 112 through 113 “In newly diagnosed advanced EOC patients, therapeutic strategies have been reported to have less than satisfactory effects on survival”. Would you please elaborate the therapeutic strategies?

Materials and methods:

1. Kindly clarify the statement “In this meta-analysis, a protocol for systematic review was not used”?

2. The timeframe of identified published studies and their geographical coverage with regard to participants of the RCTs selected for analysis?

3. Please mention the specific guideline applied to conduct this systematic review and meta-analysis and include relevant reference for the same? For instance, PRISMA or else.

Selection criteria:

� Please clarify what you meant by “irrelevant studies”? Non-English publications were included or not? If not, please specify it in that way.

� Kindly re-write the whole paragraph using medically sound and complex language. It is not necessary to repeat the same word several times. For example, the word “studies” has been used in every point of the inclusion criteria.

Data Extraction:

� What guideline was used to extract data related to the parameters e.g (name, authors, year of publication, study design, number of patients etc.)

Quality assessment:

� Kindly clarify what kind of tool was applied to evaluate the domain of risk of bias for the included RCTs?

� Please use “Statistical Analysis”, not “Statistical analyses” in the respective sub-heading.

In result section:

1. Provide detailed description of background information/study characteristics regarding the included RCTs. The figure alone is not enough.

2. The subtitles should be short and well descriptive. “Search results and characteristics and assessments of the risk of bias of the included studies”. Instead you can put “study characteristics” but remember to include detailed description of the included RCTs.

3. Table: The table is too huge and less organized.

4. The data for OS in the table in most of the rows are empty?

5. For SOLO1, the spaces are filled as “same” and no clarification is given for the item/data “same”.

6. Figures (forest plots) 2 through 4 are not clear, please provide a clear version of these figures.

Adverse effects:

� Regarding the adverse effects, please mention the details of specific adverse effects of interest?

� What guideline was followed while evaluating AEs, e.g (Common Terminology Criteria for Adverse Events: CTCAE) and include relevant reference for the same.

� Also, considering that adverse effects vary across various types of PARPis, how could you perform meta-analysis for this outcome and hence provide inference?

Conclusion:

1. Kindly clarify whether the effect of PARP inhibitors on ovarian cancer is affected by FIGO stage status, response to first-line chemotherapy, and residual macroscopic disease after de-bulking/cyto-reduction surgery?

2. Line 241, the last portion of the statement does not seem complete.

3. Line 245-249, please clarify the paragraph and include relevant references.

4. In discussion part, authors should explain the implication of the findings to the current practice.

5. Kindly consider the below recent articles on the same topic and include them in your references.

• https://pubmed.ncbi.nlm.nih.gov/32654312// DOI: 10.1111/1471-0528.16411

• https://pubmed.ncbi.nlm.nih.gov/34727316// DOI: 10.1007/s12325-021-01959-5

• https://doi.org/10.1007/s00404-021-06070-2

• https://pubmed.ncbi.nlm.nih.gov/37217940// DOI: 10.1186/s12957-023-03027-4

• https://pubmed.ncbi.nlm.nih.gov/35354431// DOI: 10.1186/s12885-022-09455-x

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Reviewer #1: No

Reviewer #2: Yes: Embaye Kidane Siele

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Impact of PARP inhibitor maintenance therapy in newly diagnosed advanced epithelial ovarian cancer: A meta-analysis

PONE-D-23-26174R1

Dear Dr Chang ,

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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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,

Asmerom Tesfamariam Sengal, MD, PhD

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: 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: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: 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: Yes

Reviewer #2: 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: Yes

Reviewer #2: Yes

**********

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: Chang et al. conducted a systematic review and meta-analysis on “Impact of PARP inhibitor maintenance therapy in newly diagnosed advanced epithelial ovarian cancer (EOC)”. They concluded that in newly diagnosed advanced EOC patients, PARPi maintenance therapy was significantly more effective in terms of survival compared to placebo group. The authors have made significant improvements in this revised manuscript while the issue of small sample size is still in its place. That being said, this study can potentially provide insights into the existing scientific knowledge pertaining to the therapeutic strategies of EOCs and is therefore recommended for publication in PLOS ONE.

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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: Kidane Siele Embaye

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