Novel Combination of Therapeutic Approaches in Advanced NSCLC with EGFR Activating Mutations

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The updated epidemiological description of lung cancer is up to date, however, the purpose of the manuscript needs to be clearer, beyond a general summary of individual drug data.

Please talk about combination therapies, such as chemotherapy+anti-EGFR, immuno-chemo, radio-chemotherapy.

Toxicity data of the various combination schedules should be reported

I suggest to include the following references about therapy in elderly patients and immunotherapy and concurrent medications

Cancers (Basel). 2022 Dec 9;14(24):6074. 

 Crit Rev Oncol Hematol. 2019 Oct;142:26-34. 

Author Response

A section has now been added discussing the rationale behind combination treatments in advanced EGFR+ NSCLC patients, in order to strengthen the idea behind this review: providing a comprehensive framework of the current state of the art in this subset of patients; the various possible combinations have now been discussed, apart from combinations including radiotherapy, since locally advanced NSCLC falls outside the scope of this paper. The suggested references have now been included.

Reviewer 2 Report

Comments and Suggestions for Authors

Dear Authors,

Thank you for sending us your manuscript.

Combination therapies involving EGFR-TKIs plus chemotherapy in patients with EGFR+ advanced NSCLC have shown promising results in several clinical trials.

It is a very interesting topic for many readers and is really well organized.

I request that the following points be considered.

 

Major point:

I would like to see a table showing at a glance the results of each clinical trial, especially the effectiveness of the combination therapies.

 

Minor points:

Page 4 shows the OS results of three clinical trials of erlotinib plus bevacizumab combo and erlotinib alone in naïve advanced EGFR+ NSCLC patients. The phase II BELIEF trial (47.0 months vs. 47.4 months) and the phase III 162 NEJ026 study (50.7 months vs. 46.2 months) show very similar results. On the other hand, the phase III BEVERLY trial showed an extremely low OS of 28.4 months vs. 23.0 months. Why would it make such a difference?

Author Response

Two separate tables reporting the results from the available trials assessing monotherapy and combination treatments in this subset of patients have now been added. The possible reasons behind the highlighted difference have now been reported.

Reviewer 3 Report

Comments and Suggestions for Authors

The review submitted by the author is nicely drafted, however, the author should take care of the following issues:

1. In several places, the author used abbreviations without giving the details. 

2. In many places digits are used with decimals like 2.000.000, Author should use the proper digit.

3. It is well-accepted that monotherapy was ineffective in treating Non-Small Cell Lung Cancers, therefore combination therapy started into practice. The author should emphasize the lacuna of each therapy, how each combination therapy overcomes that issue, and with what efficiency. 

4. The author may provide a table to illustrate the relative pros and cons of each therapy, listed in the review. 

Author Response

Each abbreviation is now explained in full. The proper digits are now reported. A section has now been added discussing the rationale behind combination treatments in advanced EGFR+ NSCLC patients highlighting, alongside with two separate tables reporting the results from the available trials assessing monotherapy and combination treatments in this subset of patients, in order to better show the pros and con of each treatment and their potential and pitfalls.