Descriptive Analysis of First-Line Non-Small Cell Lung Cancer Treatment with Pembrolizumab in Tumors Expressing PD-L1 ≥ 50% in Patients Treated in Quebec’s University Teaching Hospitals (DALP-First Study)

Round 1

Reviewer 1 Report

This study identified 279 patients of non-small cell lung cancer with PD-L1 ≥ 50% who underwent first-line chemotherapy of pembrolizumab, revealing PSF and OS were 9.4 months and 17.3 months in the real world. This study added information on pembrolizumab in the treatment of NSCLC. However, there are several flaws in this manuscript.

 

Major comment 1

There were 163 cases of patients in the unknown/NFF category in lung cancer staging, which is a confusing result in the diagnosis of NSCLC. If a review of radiographic images may be useful in revising this missing data.

 

Major comment 2

Univariate cox regression was conducted between groups. A comparison between two groups with limited cases in either arm will make the conclusion unreliable. There were only 9 cases of non-smoker in this study, a comparison between non-smoker and smoker was not statistically appropriate. 

 

Major comment 3

Body weight was associated with height of body and body mass index wouldl be more appropriate. If data on the height of body is missing, the authors should explain why the use cut-off value of 50kg. 

 

Author Response

COVER LETTER – Details of the revisions to the manuscript ID: curroncology-2225759

Title: Descriptive Analysis of first-line non-small cell Lung cancer treatment with Pembrolizumab in tumors expressing PD-L1 ≥ 50% in patients treated in Québec’s university teaching hospitals (DALP-First study)

 

Thank you for your comments. We hope that these changes will help improve the manuscript.

 

Reviewer # 1:

Details of the revision:

Major comment 1

There were 163 cases of patients in the unknown/NFF category in lung cancer staging, which is a confusing result in the diagnosis of NSCLC. If a review of radiographic images may be useful in revising this missing data.

Response to the referee:

Only one university teaching hospital had this information readily available, meaning written in the progress note, for students to collect. No imaging review could be done by pharmacy students as they are not trained for this. The authors agreed to eliminate this planned sub-group analysis as it does not have a significant impact on the manuscript.

 

Details of the revision:

Major comment 2

Univariate cox regression was conducted between groups. A comparison between two groups with limited cases in either arm will make the conclusion unreliable. There were only 9 cases of non-smoker in this study, a comparison between non-smoker and smoker was not statistically appropriate.

Response to the referee:

The authors agreed to eliminate this comparison, as there are not enough patients to conclude for this variable as noted by the reviewer.

 

Details of the revision:

Major comment 3

Body weight was associated with height of body and body mass index would be more appropriate. If data on the height of body is missing, the authors should explain why the use cut-off value of 50kg. 

Response to the referee:

The height was not a variable to be collected on the predefined collection data sheet preventing the authors from providing the body mass index. The 50 kg cut-off was used as a surrogate referring to an Italian study published in 2022[1], suggesting that a BMI below 25 was a predictor of early treatment discontinuation. A paragraph was added in the discussion to try to better explain this issue:

(…) We also observed in the Cox regression that a weight of less than 50 kg could have a negative impact on survival outcome. This analysis was added after the publication of Pasello and al. who found that a body mass index (BMI) of less than 25 is a predictor of early treatment discontinuation.[18] As the height was not collected in our study, a weight of less than 50 kg was chosen as a surrogate for a low BMI which may characterise a more fragile or frail patient population. (In our population, 33 of 279 patients (11.8%) weighed less than 50 kg and 21 of them (64%) received 4 cycles of pembrolizumab or less). We understand that not all patients weighing less than 50 kg are to be considered frail, but it is an additional information to consider when deciding to use pembrolizumab.

 

 

1. [1] Pasello G, Lorenzi M, Calvetti L, Oliani C, Pavan A, Favaretto A, Palazzolo G, Giovanis P, Zustovich F, Bonetti A, et al. Multicenter Real-World Study on Effectiveness and Early Discontinuation Predictors in Patients With Non-small Cell Lung Cancer Receiving Nivolumab. Oncologist. 2022 Jun 8;27(6):e484-e493. doi: 10.1093/oncolo/oyac051. 

 

Reviewer 2 Report

Thank you for the real-world data. The followings are some concerns and comments have been pointed out that the authors may want to consider.

1) Lines 87-88 methods and study designs: I’d suggest the authors generate a workflow scheme to make it clearer.

2) Line 200 Table 2: Please use italic p as it refers to a p-value throughout the manuscript.

3) Line 333: I’d suggest the authors enrich necessary discussion and involve other potential immunotherapy, for example, PD1-Vaxx (PMID: 35646678, please check all other related papers by yourself) which is in the clinical trial.

Author Response

COVER LETTER – Details of the revisions to the manuscript ID: curroncology-2225759

Title: Descriptive Analysis of first-line non-small cell Lung cancer treatment with Pembrolizumab in tumors expressing PD-L1 ≥ 50% in patients treated in Québec’s university teaching hospitals (DALP-First study)

 

Thank you for your comments. We hope that these changes will help improve the manuscript.

 

Reviewer # 2:

Details of the revision:

1) Lines 87-88 methods and study designs: I’d suggest the authors generate a workflow scheme to make it clearer.

Response to the referee:

All patients receiving at least one dose of pembrolizumab monotherapy during the data collection period for 1^st line advanced or metastatic NSCLC were included. Therefore, we did not add a workflow scheme as suggested but a sentence to clarify how information was collected using a predefined collection data sheet:

(…) All patients 18 years or older that initiated treatment and received at least one dose of pembrolizumab monotherapy for the first line treatment of a histologically proven, advanced (stage III) or metastatic (stage IV) NSCLC with a PD-L1 ≥50% between November 1^st 2017 and October 31^st 2019 were reviewed. Patients were excluded if they had previously received treatment with an EGFR or ALK inhibitor, if they received pembrolizumab as part of an immuno-chemotherapy combination or if pembrolizumab was given as part of a clinical trial. Information found in patients’ files of all eligible patient were entered on a standardized collection sheet. (…)

 

 Details of the revision:

2) Line 200 Table 2: Please use italic p as it refers to a p-value throughout the manuscript.

 

Response to the referee:

The font was modified according to the comment from the reviewer

 

Details of the revision:

3) Line 333: I’d suggest the authors enrich necessary discussion and involve other potential immunotherapy, for example, PD1-Vaxx (PMID: 35646678, please check all other related papers by yourself) which is in the clinical trial.

Response to the referee:

The sentence in the conclusion was enriched to cover for other examples as proposed

Reviewer 3 Report

Attached is my comments to the authors.

Comments for author File: Comments.pdf

Author Response

COVER LETTER – Details of the revisions to the manuscript ID: curroncology-2225759

Title: Descriptive Analysis of first-line non-small cell Lung cancer treatment with Pembrolizumab in tumors expressing PD-L1 ≥ 50% in patients treated in Québec’s university teaching hospitals (DALP-First study)

 

Thank you for your comments. We hope that the changes made following the comments of the reviewers will help improve the manuscript.

1. The data presented is for an unselected and real-world data. The 3 patients were presented and treated as PD-L1>50%, even if this was not the case. That is why the were included.
2. A multivariate regression was made but it did not bring more to the data. Due to "lack of space" it was left out of the final manuscript.
3. Il would of been a good idea, but we chose not to go in this direction.
4. A paragraphe was added under table 5 adressing this point. 

Reviewer 4 Report

Dear Authors,

Great Study. It adds many valuable insights into what already is know about Pembrolizumab. It adds strength to the effective use of Pembrolizumab as an effective immunotherapy candidate. The most important part of the study was that authors tried the weight based dosage of Pembro and found similar results as in max capped dose. This will reduce financial burden on the patients and they will be able to afford better care. It also reduces the overall health care cost.

Overall, Good Study and adds lot of value to the use of Pembrolizumab in NSCLC patients.

Author Response

COVER LETTER – Details of the revisions to the manuscript ID: curroncology-2225759

Title: Descriptive Analysis of first-line non-small cell Lung cancer treatment with Pembrolizumab in tumors expressing PD-L1 ≥ 50% in patients treated in Québec’s university teaching hospitals (DALP-First study)

 

Thank you for your comments. We hope that the changes made following the other reviewers comments will help improve the manuscript.

Round 2

Reviewer 1 Report

 I have no additional comment on this manuscript.

Author Response

Thank you very much for the time you spent to read and comment our article.

Your comments were very helpful to us.