Improving Time-to-Treatment for Advanced Non-Small Cell Lung Cancer Patients through Faster Single Gene EGFR Testing Using the Idylla™ EGFR Testing Platform

Round 1

Reviewer 1 Report

This study compares a single gene EGFR test to a multi-gene panel to examine the time to treatment for patients with advanced lung cancer. This is an important issue that needs more research.

introduction- Discuss the prevalence of EGFR and other mutations in lung cancer. EGFR mutations are expected to be about 30%, was that the case in this cohort? please discuss this in the discussion.

Figures- Figure 1 is too small, hard to read, and needs more resolution/clarity. Figure 1 needs significant improvements. All of the distribution figures are very hard to read, consider changing the chart type to a different style and increasing resolution. A supplemental table with all the patients, their respective TAT and mutations identified would further enhance this study.

Methods- more transparency on which patients were excluded and why, would be beneficial.  would highlight which pts from which group were excluded. This will be easier for readers to read and be fully clear about the outlier patients which is reasonable. Clarify in methods if both panels were done simultaneously or was it done sequentially? I assume its simultaneous but further clarification would be helpful.

Results- "In the overall trial cohort, 31 patients received treatment after receiving the Idylla test 191

result but before the OncoPanel result, with an average TTT savings of 7.6 days. In 52% 192
(17/33) of EGFR positive patients, treatment was initiated after receiving the Idylla test 193
result but before the OncoPanel result. The TTT was 8.2 days on average for these pa- 194
tients. In patients who had a PD-L1 TPS of >50%, only 5% (1/19) had treatment initiated 195
after the Idylla test result and before the Oncopanel results." Results section is hard to follow. If 31 patients received treatment after the Idylla test is this because these patients were EGFR positive? The rationale for PDL1 positive group is unclear. What about patients that had oncogenic drivers other than EGFR? Adding the prevalence of EGFR mutation and how many non-EGFR mutations were identified in the trial cohort will be helpful since patients with oncogenic drivers with the exception of KRAS should not go on immunotherapy. Please include TTT for non-EGFR patients as well in the trial cohort.

Discussion- "The decrease in TTT can not only improve outcomes but also prevent death in those whose disease progresses very fast." This sentence would need to be further softened. Outcomes and disease progression would be out of the scope of this study. Can be rephrased as we speculate that a decrease in TTT could potentially improve outcomes however that could not be assessed in this study and can examine in future studies. What about patients that were EGFR negative and results of the onco panel were needed, this data would need to be discussed as well.

Minor change- "Genetic" testing is usually used for germline testing and "genome" testing is more appropriate here for identifying somatic variants. In this case, it could be called a single gene test since only EGFR is being tested. Consider "Improving Time-to-Treatment for Advanced Non-Small Cell Lung Cancer Patients through Faster single gene Testing using the 3

new Idylla™ EGFR Testing Platform.

  Overall the study is an important one. Improving figures and re-writing the results, and methods with greater clarity will make this easier to read.

Author Response

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Author Response File: Author Response.docx

Reviewer 2 Report

This article provides useful recommendations for streamlining NSCLC genetic testing and reducing TTT. The insights can have a tangible impact on NSCLC patient treatment and outcomes. I suggest the following minor edits:

1.       It could be helpful to include a diagram or table illustrating the high-level characteristics of the trial, such as the number of patients and treatments of each arm, overall objectives of the trial, etc.

2.       Please indicate what TAT stands for in the Abstract, which is when the acronym first shows up in the article.

3.       The legends of some figures, especially figure 1, are very fuzzy and even illegible. Make sure that they are fixed in the final publication.

4.       I recommend adding a diagram comparing the genetic testing steps, the time each step takes, and the total TTT with and without applying the recommendation. Such comparison can clearly show the time improvements by using the Idylla EGFR test.  

Author Response

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Author Response File: Author Response.docx

Reviewer 3 Report

Summary

The authors compared the Idylla EGFR testing group and Oncopanel testing group. Their think that the Idylla EGFR test as part of the molecular testing repertoire in advanced-stage NSCLC patients could reduce TTT. 

 

 

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Major issues:

 

For the TTT, only 30% of patients are EGFR+, and some patients of these patients with EGFR+ low-frequency mutations, which can not be detected by the Idylla test; then, most of the patients could not be suitable for the decision by the Idylla test.  In conclusion, "this study demonstrates that on average, TTT from molecular testing initiation can be reduced by 48% in EGFR positive NSCLC patients, and 301 by 25% in all advanced-stage NSCLC patients."

Authors should better give a discussion about it or design a better solution idea in the text.

 

The idea which using the Idylla EGFR mutation testing in NSCLC has been provided in many previous studies, and it is surprising that the authors do not discuss them and refer to these literatures; for example:(PMID: 28554746; 34898548; 31715539; 31445213; 28153953; 31296605). The authors should involve related studies in the introduction and associated parts.

 

The Figures in this study are very homogeneous, and there is no other analytical evidence to support a solid conclusion.  It would be better to add the statistical analysis comparison figures to compare the differences between the two groups visually.

 

 

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other issues:

The first abbreviations should give the full name.

 

The resolution of the figures is not good enough. 

 

The layout and size of the Figures and tables in the manuscript are not standardized. 

Author Response

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Author Response File: Author Response.docx

Reviewer 4 Report

The article "Improving time-to-treatment for advanced non-small cell lung cancer patients through faster genetic testing using the new Idylla EGFR testing platform" is interesting and the results presented indeed may have an impact on a clinical use of available tests and methods. Although I support the idea that the variety of diagnostic tests available to clinicians provide better opportunities, I have several questions and I hope they'll help to improve the paper. 

1. Line 35m the expression "very sick" seems to be rather colloquial, non-clinical. Can you be more specific please? What does it mean "very sick"?

2. Paragraph about the Idylla platform (lines 55-61) should be relocated to the materials and methods, and described there together with other methods used. I don't see the reason why this one is favoured over another one in the introduction, while on this stage it should be treated as equal. 

3. In materials and methods I don't see enough information about the Illumina sequencing (depth? coverage? what exactly has been sequenced - entire gene? selected exons?) 

4. Figure 1 - first sentence; comparison of what? time? Not clear. 

5. Figures are generally very small, difficult to read properly.

6. Idylla platform - does it require separate device or can be performed only on any qPCR device? Not enough information.

7. Nearly nothing about the costs. Is it cost-effective or just faster? 

 

 

Author Response

Please see the attachment. 

Author Response File: Author Response.docx