Clinical Outcomes of Poly(ADP–Ribose) Polymerase Inhibitors as Maintenance Therapy in Patients with Ovarian Cancer in the Southeastern Region of Korea

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Thank you very much for allowing me to review this article. This article is well written, with clear and understandable information. I think it is really  interesting  Real-world data is always needed to support literature data.

Nevertheless, there are some ideas that I think need clarification or modifications.

 

Abstract, line 33-34: do you think Conclusion si concrodant with the rest of teh abstract? Perhaps conclussion should focus more on your results, no tin comparing with literatura, thatis not mentioned anywhere in the abstract. Please, think about rewriting conclusion more concrdant to the rest of the abstract.

 

Introduction, line 50: “The Standard treatment for patients with Advanced ovarian càncer involves primary cytorreeductive surgery followed by platinum-based chemotherapy”. I think “Standard” is not perhaps the best adjective here, please change to another more suitable lika optimal or something like that Also, somewhere in this paragraph it should be added that this treatment refers to advanced cancer but not unresectable metastatic cancer. Please modify and specify it..

Introduction, line 55 “ovarian càncer it tipically fatal due to drug resistance” Please make sure that this is the only cause of recurrence, or otherwise modify the sentence.

 In results line 122 It is described that surgery is performed with neoadjuvant or adjuvant chemotherapy, but in material and methods  lines 81 and 82 you only talk about post-surgery adjuvant chemotherapy, not neoadjuvant chemotherapy. Please specify the inclusion and exclusion criteria well and quantify patients of each kind f surgery

Discussion, line 311, Do you think that the fact that the sample cannot be extrapolated to the rest of the world's population could also be a limitation? Please specify.

Line 318 conclussion, Please, evaluate if the conclusion is precisely that, because the comparison is indirect and therefore we cannot assume it as such.

Author Response

Thank you very much for taking the time to review this manuscript. Please find the detailed responses below and the corresponding revisions/corrections highlighted/in track changes in the re-submitted files.

Comment 1: Abstract, line 33-34: do you think Conclusion si concrodant with the rest of teh abstract? Perhaps conclussion should focus more on your results, no tin comparing with literatura, thatis not mentioned anywhere in the abstract. Please, think about rewriting conclusion more concrdant to the rest of the abstract.

Response 1: Thank you for making this comment. The authors delete the non-concordant sentence in conclusion section (lines 381-382)

 

Comment 2: Introduction, line 50: “The Standard treatment for patients with Advanced ovarian càncer involves primary cytorreeductive surgery followed by platinum-based chemotherapy”. I think “Standard” is not perhaps the best adjective here, please change to another more suitable lika optimal or something like that Also, somewhere in this paragraph it should be added that this treatment refers to advanced cancer but not unresectable metastatic cancer. Please modify and specify it.

Response 2: Thank you for this valuable comment. The authors rewrite (line 68; optimal) and add (line 71; unresectable metastatic tumors) the suitable words.

 

Comment 3: Introduction, line 55 “ovarian càncer it tipically fatal due to drug resistance” Please make sure that this is the only cause of recurrence, or otherwise modify the sentence.

Response 3: Thank you for this comment. The authors rewrite the sentence. (line 75)

 

Comment 4: In results line 122 It is described that surgery is performed with neoadjuvant or adjuvant chemotherapy, but in material and methods lines 81 and 82 you only talk about post-surgery adjuvant chemotherapy, not neoadjuvant chemotherapy. Please specify the inclusion and exclusion criteria well and quantify patients of each kind f surgery

Response 4; Thank you for important comment. The authors rewrite the sentence. (line 142-143)

 

Comment 5: Discussion, line 311, Do you think that the fact that the sample cannot be extrapolated to the rest of the world's population could also be a limitation? Please specify.

Response 5: Thank you and we absolutely agree with this comment. The authors rewrite the sentence (line375-376)

 

Comment 6: Line 318 conclusion, Please, evaluate if the conclusion is precisely that, because the comparison is indirect and therefore we cannot assume it as such.

Response 6: The authors partly agree with the comment, but we think it is meaningful as a real word data in the use of PARP inhibitors in the national health insurance environment of Korea despite small sample size, relatively unrepresentative cohort, short follow-up period.

Reviewer 2 Report

Comments and Suggestions for Authors

The authors conducted a retrospective study to investigate real-world clinical outcome of PARP inhibitor as first-line maintenance therapy in epithelial ovarian cancer. Ninety-six patients were included, and the mPFS was 45.3 months. Patients with BRCA mutations or underwent primary debulking cytoreductive surgery were associated with better outcome.

The authors concluded that in real-world, PARP inhibitors (Olaparib and Niraparib) as frontline maintenance therapy resulted in a comparable outcome to previous reported data, and the safety profiles were acceptable.

 

Here are some suggestions:

1.      If possible, can you describe how many patients in maintenance phase receive bevacizumab combine with PARP inhibitor? Besides, for patients treated with bevacizumab, is it a prognostic factor?

2.      If available, can you provide the principle to decide the starting dose of PARP inhibitor?  In your cohort, Olaparib was started with either 300mg BID or 200mg BID, and niraparib was started with 300mg QD or 200mg QD.

Bedsides, in table 1, the starting dose of Olaparib was 300mg BID(tablet) and 400mg BID (capsule), while the in the manuscript, 138^th line, Olaparib was started with 300 or 200mg BID. Please clarify this dosage difference. 

3.      In your cohort, most of the patients were BRCA wild type, did they receive HRD testing? If available, please provide this information.

Author Response

Thank you very much for taking the time to review this manuscript. Please find the detailed responses below and the corresponding revisions/corrections highlighted/in track changes in the re-submitted files.

Comment 1: If possible, can you describe how many patients in maintenance phase receive bevacizumab combine with PARP inhibitor? Besides, for patients treated with bevacizumab, is it a prognostic factor?

Response 1: Thank you for the important and valuable comments. In our study, there are no patients receiving both bevacizumab and PARP inhibitor in maintenance phase. Bevacizumab was only used as adjuvant treatment, and no prognostic factor in the multi-variate analysis.

 

Comment 2:  If available, can you provide the principle to decide the starting dose of PARP inhibitor?  In your cohort, Olaparib was started with either 300mg BID or 200mg BID, and niraparib was started with 300mg QD or 200mg QD.

Bedsides, in table 1, the starting dose of Olaparib was 300mg BID(tablet) and 400mg BID (capsule), while the in the manuscript, 138th line, Olaparib was started with 300 or 200mg BID. Please clarify this dosage difference.

Response 2: Thank you for the important comments. We apologize for the confusion. The starting dose of Olaparib was 300mg BID(tablet) and 400mg BID (capsule). The starting dose of Niraparib was 200mg for bodyweight <77 kg and/or platelet count <150 × 103/μL at baseline and 300 mg otherwise as. We rewrite the sentence in line 146.    

 

Comment 3: In your cohort, most of the patients were BRCA wild type, did they receive HRD testing? If available, please provide this information.

Response 3: Thank you for the comments. Unfortunately, in Korea, the Myriad MyChoice HRD test was not introduced due to problems such as insurance and cost, so HRD test could not be performed, so PARP inhibitor was administered according to BRCA test results.

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

Accept for publication.