Round 1

Reviewer 1 Report

1. Please consider rephrasing this sentence in the penultimate paragraph in the introduction section for better clarity: 
In 2015 Shankar, et al. reported 21-, 15- and 8-month Progression-Free Survival (PFS) in first-line for the chemoendocrine therapy, AIs or capecitabine alone, respectively [28]

2. Please improve the quality of all figures by uploading higher resolution images.

3. Figures 1A and 1B should have identical legends (including bold fonts)

4. Figure 3 was erroneously labeled figure 4.

5. "Figure 4": Consider increasing font size for axes labels and legends

6. Discussion section, 4th paragraph: 
"PFS for XELIA group was similar to what has been reported for CDK 4/6 inhibitors [39] and significantly longer than for the AI group (29.37 vs. 20.04 months), however there was no difference in OS."

Here the authors refer " Fulvestrant-Palbociclib vs Letrozole-Palbociclib as Initial Therapy for Endocrine-Sensitive, Hormone Receptor-Positive, ERBB2-Negative Advanced Breast Cancer: A Randomized Clinical Trial" manuscript. 

Please draw comparisons between a randomized clinical trial and a retrospective study as yours, only after discussing the similarities and differences in the patient population. Only then mention comparative PFS between XELIA group and CDK 4/6 inhibitors group. There is a huge difference in demographic diversity between these two studies.

 

1. Correct "hemathological" to hematological in the following sentence in Results section 3.3:
"Hemathological and Non-Hemathological Adverse Eventes from G2 to G4 (CTCAE v5.0) are represented by frequency in every treatment in Figure 3. "

2. Same spelling error in "figure4" title: 
"Figure 4.A. Hemathological Adverse Event graded G2-G4. 4.B. Non-Hemathological Adverse Events graded G2-G4 frequency of Adverse Event by treatment group is represented in both graphics."

3. Correct "eventes" to "events" in the same sentence in point 1 (above):

"Hemathological and Non-Hemathological Adverse Eventes from G2 to G4 (CTCAE v5.0) are represented by frequency in every treatment in Figure 3. "

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

I believe that drawing conclusions comparing these regimens based on a very small retrospective sample is not clinically relevant. Comparison of progression free survival, response rates, and toxicities in such small retrospective non-randomized patient populations is in my opinion not drawing valid conclusions. I would recommend that you focus on the efficacy and safety data you have in your retrospective XELIA population alone, rather than making comparisons to other patient groups. 

some revisions are needed-minor changes

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 3 Report

The authors provide a retrospective study in Her2- HR+ patients treated with aromatase inhibitor and capecitabine. The overall survival is not significantly altered across the 3 groups while toxicity is higher in the combination XELIA group. Having said that the PFS is increased in the XELIA group compared to others. Before publication of the data following comments should be addressed:

1. It needs to be stressed in the abstract and the title that this is a potential therapy regimen for patients who do not have access to conventional approved therapy such as CDK4/6

2. The narrative of the paper is to portray this as an excellent new therapy for metastatic breast cancer showing synergistic combination effect. This needs to be changed in introduction and abstract to reflect the result. Only primary end point is met while secondary endpoint of OS is not met. The authors should not try to oversell the study and present the data as is with its caveats.

3. There is no data to compare with CDk4/6 inhibitors so the authors should not try to pitch that the response is comparable to CDK4/6 inhibitors.

Minor typological and grammatical errors should be fixed by thorough proofreading of the manuscript

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

I still believe it is important to emphasize in the abstract and the conclusions that this is a very small, retrospective, non-randomized study for which comparisons of progression free survival and overall survival are not necessarily generalizable to a larger population. You conclude the abstract with "Progression-Free Survival and Overall Response Rate increased in XELIA regimen than aromatase inhibitor or capecitabine alone". I feel this is a very misleading interpretation of data when it is derived from a small retrospective study. Rather, I feel you should say that in this small retrospective data base, there is a suggestion that PFS and OS may be improved in the XELIA regimen compared to the single agents, but that this would need to be confirmed in a randomized trial. I do not feel that comparisons of PFS and OS can be generalized without large randomized studies.

Author Response

Dear Reviewer, 

Thank you for your constructive comments. The suggested changes were done in the abstract to emphasize the limitations of our study.

Reviewer 3 Report

Comments were addressed

Author Response

Dear Reviewer, 

Thank you for your previous comments.