Braf-Mutant Melanomas: Biology and Therapy
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThe authors present a compelling paper on the role of BRAF mutation in melanomas. It is well-written and easy to read, although similar reviews have been published in recent years. I recommend adding more detail to provide readers with a comprehensive update on the latest developments in this field. Specifically:
- In the introduction, please discuss the dermoscopic features, as you have referenced the paper (DOI: 10.1111/ced.15113) without including specifics. It is crucial to highlight that mutational status cannot be effectively predicted based on early dermoscopic features (refer to DOI: 10.1111/ijd.16710).
- For stage III, include comments on the improved trends of targeted therapies in stage IIID BRAF-positive patients compared to adjuvant anti-PD1 therapy (COMBI-AD data).
- Note the lack of significant benefit in relapse prevention with adjuvant regimens in patients with AJCC 8th edition stage IIIA, whether with pembrolizumab (supplementary data: https://doi.org/10.1016/j.ejca.2024.114327) or targeted therapies (ASCO 2020, Hauschild interim analysis).
- Relate these findings to trends noted in the multicentric study presented at ASCO 2023 (https://doi.org/10.1200/JCO.2023.41.16_suppl.9518).
- Comment on the absence of this data in the 10-year final analysis of COMBI-AD, where stage-specific results were only reported for OS and not RFS in accordance with AJCC 8th edition (supplementary data: DOI: 10.1056/NEJMoa2404139).
- Incorporate findings from a recent real-life study demonstrating comparable trends in real-life data for TT/IT (https://doi.org/10.3390/cancers16173095), emphasizing the need for new biomarkers to refine patients' therapy selection.
- In the therapy cost section, discuss the issue of NNT/NNH (https://doi.org/10.1097/XCS.0000000000000088)(https://doi.org/10.1016/j.ejcskn.2024.100021).
Author Response
Reply to reviewer 1
The authors present a compelling paper on the role of BRAF mutation in melanomas. It is well-written and easy to read, although similar reviews have been published in recent years. I recommend adding more detail to provide readers with a comprehensive update on the latest developments in this field. Specifically:
- In the introduction, please discuss the dermoscopic features, as you have referenced the paper (DOI: 10.1111/ced.15113) without including specifics. It is crucial to highlight that mutational status cannot be effectively predicted based on early dermoscopic features (refer to DOI: 10.1111/ijd.16710).
Response: In the introduction, dermoscopic features of BRAF-V600K and -V600E melanomas were discussed.
- For stage III, include comments on the improved trends of targeted therapies in stage IIID BRAF-positive patients compared to adjuvant anti-PD1 therapy (COMBI-AD data).
Response: For stage III, comments were added to the COMBI-AD trial.
- Note the lack of significant benefit in relapse prevention with adjuvant regimens in patients with AJCC 8th edition stage IIIA, whether with pembrolizumab (supplementary data: https://doi.org/10.1016/j.ejca.2024.114327) or targeted therapies (ASCO 2020, Hauschild interim analysis).
Response: The lack of significant relapse prevention for stage IIIA patients was now discussed.
- Relate these findings to trends noted in the multicentric study presented at ASCO 2023 (https://doi.org/10.1200/JCO.2023.41.16_suppl.9518).
Response: The ASCO 2023 paper indicated by the reviewed was now mentioned and carefully analyzed.
- Comment on the absence of this data in the 10-year final analysis of COMBI-AD, where stage-specific results were only reported for OS and not RFS in accordance with AJCC 8th edition (supplementary data: DOI: 10.1056/NEJMoa2404139).
Response: Absence of data on RFS according to tumor stage in the COMBI-AD trial was now underlined.
- Incorporate findings from a recent real-life study demonstrating comparable trends in real-life data for TT/IT (https://doi.org/10.3390/cancers16173095), emphasizing the need for new biomarkers to refine patients' therapy selection.
Response: The paper reporting real-life data on TT/IT adjuvant treatment of resectable melanoma patients, stage III/IV was now mentioned and analyzed in detail.
- In the therapy cost section, discuss the issue of NNT/NNH (https://doi.org/10.1097/XCS.0000000000000088)(https://doi.org/10.1016/j.ejcskn.2024.100021).
Response: In the therapy cost section, mention was now made to the two papers suggested by the referee.
Reviewer 2 Report
Comments and Suggestions for AuthorsIt is an excellent paper that tackles a topic of great interest from dermato-oncology: melanomas with BRAF-mutant type, with a detailed description of mutations found in melanomas. Also, the new stage-adjusted melanoma treatments were closely analyzed.
Hereby please find my comments regarding the paper:
1. The abstract is well presented, but with some editing errors (about 90% - line 11). Please change the term “due” with “mainly” from the sentence: ”The incidence of melanoma, the most lethal form of skin cancer, has increased due to ultraviolet exposure”, because the UV-radiations are not the single cause of increasing melanoma incidence.
2. In the introduction section you have not included the nodular melanomas in none of the low- or high-risk category. Please complete.
3. In the Therapy of BRAF-mutant melanomas and conclusion sections some editing errors occurred (Ipelimumab - line 318, $-year – line 839, oranti-PDL1 – line 868, improvcement – line 884). Also, I would insert to ESMO Congress the year 2024.
4. The new treatments used for melanomas are well presented, with clear studies evidence.
5. The conclusions are well presented and the references are appropriate.
Author Response
Reply to referee 2
It is an excellent paper that tackles a topic of great interest from dermato-oncology: melanomas with BRAF-mutant type, with a detailed description of mutations found in melanomas. Also, the new stage-adjusted melanoma treatments were closely analyzed.
Hereby please find my comments regarding the paper:
1. The abstract is well presented, but with some editing errors (about 90% - line 11). Please change the term “due” with “mainly” from the sentence: ”The incidence of melanoma, the most lethal form of skin cancer, has increased due to ultraviolet exposure”, because the UV-radiations are not the single cause of increasing melanoma incidence.
Response: The abstract was modified as suggested by the reviewer.
2. In the introduction section you have not included the nodular melanomas in none of the low- or high-risk category. Please complete.
Response: Nodular melanomas are now discussed in the Introduction section.
3. In the Therapy of BRAF-mutant melanomas and conclusion sections some editing errors occurred (Ipelimumab - line 318, $-year – line 839, oranti-PDL1 – line 868, improvcement – line 884). Also, I would insert to ESMO Congress the year 2024.
Response: Editing errors were corrected, as suggested.
Round 2
Reviewer 1 Report
Comments and Suggestions for AuthorsThe authors have addressed all the comments.
Reviewer 2 Report
Comments and Suggestions for AuthorsDear authors,
You made all the changes that I recommended. Congratulation for your work.
