Abemaciclib Therapy Using the MonarchE Criteria Results in Large Numbers of Excess Axillary Node Clearances—Time to Pause and Reflect?
, Nisha Ali 1, Vicky P. Taxiarchi 2, Rajiv V. Dave 1,3 and Ashu Gandhi 1,3,*Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThe study entitled "Abemaciclib Therapy Using The MonarchE Criteria Results In Large Numbers Of Excess Axillary Node Clearances; Time To Pause And Reflect?" by D Ahari et al. evaluates the necessity and outcomes of cANC in women with ER+HER2- breast cancer to assess eligibility for abemaciclib therapy under monarchE criteria.
Analyzing 229 cases from 2016-2022, the study finds that 39.3% of women would qualify for abemaciclib based on initial surgery and SNB alone. However, of the 139 women who required cANC to potentially meet abemaciclib eligibility, only 15 (10.8%) met the criteria post-cANC.
The study highlights that nearly 90% of women undergoing cANC did not gain clinical benefit from the procedure, exposing them instead to the risk of significant morbidity, including lymphoedema.
I have some comments:
- Overall the English language needs moderate revisions. Some parts are difficult to follow/understand. "We examine how many 30 women need to undergo an axillary node clearance in order for 1 woman to clinically benefit from 31 the procedure and show that for every 10 women undergoing axillary node clearance surgery, only 32 1 eventually qualifies for abemaciclib." It is not clear. Line 110, "Cognisant" What does it mean?
- I undestand that you based your research on current national guidelines. However, what kind of guidelines were you using? Were breast cancer patients with 1-2 positive SLNs treated with cANC ? Does it depend on type of breast cancer surgery? Breast-conserviong surgery or mastectomy? The Z0011 clinical trial criteria were already widely adopted when you study started.
- Overall the Introduction section is too long. Lines 94-109 are redundant. Please move citations from AMAROS trial to the Discussion section.
- In the inclusion criteria, did you consider only breast cancer patients with cN0 disease? And how was the loco-regional staging performed? If so, it is fundamental to specify this in the Materials and Methods!
- Some criteria for cANC in early-stage breast cancer patients in the light of the new combinations therapies (abemaciclib + chemotherapy + endocrine treatment) were explored by this study PMID: 38883951. Please add this in the Discussion as it would greatly improve the quality of your study.
- There are many more limitations in your retrospective cohort study! Please state all of them.
- The Conclusions are too long. Re-write them.
Comments on the Quality of English LanguageOverall the English language needs moderate revisions. Some parts are difficult to follow/understand. "We examine how many 30 women need to undergo an axillary node clearance in order for 1 woman to clinically benefit from 31 the procedure and show that for every 10 women undergoing axillary node clearance surgery, only 32 1 eventually qualifies for abemaciclib." It is not clear. Line 110, "Cognisant" What does it mean?
Author Response
Many thanks, please see attachment
Author Response File: 
Author Response.pdf
Reviewer 2 Report
Comments and Suggestions for AuthorsThe manuscript presented for review is an interesting analysis of the risk/benefit ratio of using complete axillary lymphadenectomy solely to check the eligibility of estrogen positive breats cancer patients to receive an cdk4/6 inhibitor now available and introduced in many national guidelines.
The manuscript is well organized, the methodology is clearly presented and the conclusions are supported by the results.
As a personal opinion I believe that many targeted Therapies skip some steps before being introduced in clinical guidelines. We have to take a minute an think that many of these agents have their own potential risks and if you add to that the risk of diagnostic procedures (in this case complete axillary lymphadenectomy) and the lack of an overall survival benefit, their introduction in guidelines should be tempered by clinical evidence. This particular agent also has an extremely high number of patients that need to be treated to get 1 patient with actual benefits (as stated by the original authors of Monarch study) further clouding the clinical benefits of therapy.
My suggestion for improvement of the manuscript are as follows :
1.please remove the actual codes by which the electronic database was searched - it presents no interest since different electronic systems are used in different countries and the codes vary.
2. Please add în discussion a part about the risk of using surrogate endpoints like progression free survival in the approval process of Oncologic therapeutic agents. The majority of agents approved in this manner proved not to have any overall survival benefits when the mature data was available. Meanwhile these agents are introduced in national guidelines with minimal regard to costs or risk.
3. Minor typos
Author Response
Many thanks, please see attachment
Author Response File: Author Response.pdf
