UMIN-CTR Clinical Trial

Public title

Regimen-dependent impact of sex and smoking history on overall survival in advanced non-small cell lung cancer

Acronym

Regimen-dependent impact of sex and smoking history on overall survival in advanced non-small cell lung cancer

Scientific Title

Regimen-dependent impact of sex and smoking history on overall survival in advanced non-small cell lung cancer

Scientific Title:Acronym

Regimen-dependent impact of sex and smoking history on overall survival in advanced non-small cell lung cancer

Region

Japan

Condition

advanced non-small cell lung cancer

Classification by specialty

Pneumology

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

The influence of demographic factors such as sex and smoking history on the efficacy of ICIs has been the focus of extensive research. Some concluded that there is no statistically significant difference in ICI efficacy between smokers and non-smokers. However, some systematic reviews suggest that smokers may derive greater benefit from ICI therapy. This observation is likely attributable to the fact that patients with a smoking history often exhibit a higher tumor mutational burden (TMB), which is associated with enhanced ICI efficacy. On the other hand, the impact of sex on ICI effectiveness remains unclear, with conflicting results reported in the literature. Specifically, some studies suggest greater efficacy in male patients, while others indicate a more pronounced benefit in female patients.
The debate surrounding the influence of sex and smoking history on ICI efficacy remains unresolved. One potential explanation for these conflicting findings is that the effects of sex and smoking history may vary depending on the specific treatment regimen used. ICIs can be administered as monotherapy, in combination with platinum-based chemotherapy, or alongside CTLA-4 inhibitors, each with distinct mechanisms of immunological action.
In this study, we aim to evaluate the impact of sex and smoking history on overall survival (OS) hazard ratios (HR, HRos) in patients with advanced NSCLC treated with ICIs across all treatment regimens. Specifically, we seek to clarify how different treatment regimens influence the effects of sex and smoking history on patient survival.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

rate of hazard ratio (RHR) of OS

Key secondary outcomes

Study type

Others,meta-analysis etc

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

Not applicable

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

Patients
This study will include patients with advanced non-small cell lung cancer (NSCLC), encompassing metastatic, relapsed, and locally advanced diseases.
adenocarcinoma, squamous cell carcinoma, large cell carcinoma, and non-squamous cancers are considered eligible. Studies exclusively targeting large cell neuroendocrine carcinoma (LCNEC) will be excluded.

Treatment
The experimental regimens must contain immune checkpoint inhibitors (ICIs), including PD-1 inhibitors, PD-L1 inhibitors, or CTLA-4 inhibitors. LAG-3 inhibitors will be excluded as no phase III trials are available at the time of the search. The analysis will include ICI monotherapy, dual ICI combinations, and ICIs combined with cytotoxic therapies. Both first-line and subsequent lines of therapy will be eligible.
The control regimens must consist of cytotoxic therapies, placebo, or best supportive care. Molecular targeted therapies and ICIs must not be included in the control regimen. Based on the treatment regimens, studies will be categorized into three groups: (1) platinum-doublet chemotherapy plus one PD-(L)1 inhibitor, (2) ICI monotherapy, and (3) regimens containing CTLA-4 inhibitors.

Study design and reporting style
This study will include phase III trials (or phase II/III trials) published as full research article.

Key exclusion criteria

Studies exclusively targeting large cell neuroendocrine carcinoma (LCNEC) will be excluded.
Chemoradiotherapy and perioperative treatments, including adjuvant or neoadjuvant therapy, will be excluded.
Abstracts and non-English publications will be excluded. Studies that do not provide hazard ratios (HRs) for subgroups based on sex and smoking history will also be excluded.

Target sample size

Name of lead principal investigator

1st name	Nobuyuki
Middle name
Last name	Horita

Organization

Yokohama City University Hospital

Division name

Chemotherapy Center

Zip code

236-0004

Address

3-9, Fukuura, Kanazawa, Yokohama, Japan

TEL

045-787-2800

Email

horitano@yokohama-cu.ac.jp

Name of contact person

1st name	Nobuyuki
Middle name
Last name	Horita

Organization

Yokohama City University Hospital

Division name

Chemotherapy Center

Zip code

236-0004

Address

3-9, Fukuura, Kanazawa, Yokohama, Japan

TEL

045-787-2800

Homepage URL

Email

horitano@yokohama-cu.ac.jp

Institute

Yokohama City University Hospital

Institute

Department

Personal name

Organization

Yokohama City University Hospital

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Yokohama City University Hospital

Address

3-9, Fukuura, Kanazawa, Yokohama, Japan

Tel

045-787-2800

Email

horitano@yokohama-cu.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2024

Year

11

Month

25

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Preinitiation

Date of protocol fixation

2024

Year

11

Month

25

Day

Date of IRB

Anticipated trial start date

2024

Year

11

Month

25

Day

Last follow-up date

2025

Year

12

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Statistics
The rate of hazard ratio (RHR) will be calculated using HRs for sex and smoking history subgroups, based on the formula below: RHR = HRos_men / HRos_women. The 95% confidence interval for the RHR will be derived using the following SE: SE_RHR = (SE_men^2 + SE_women^2)^.5. The RHR for smoking history will be calculated similarly, using non-smokers as the reference.
Meta-analyses will be conducted using RevMan version 5.4.1. The choice between fixed-effect and random-effects models will be determined based on overall heterogeneity. Subgroup heterogeneity will be a key focus of our analysis. Heterogeneity will be assessed using the I2 statistic and the P-value for heterogeneity.

Registered date

2024

Year

11

Month

25

Day

Last modified on

2024

Year

11

Month

25

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000064287