UMIN-CTR Clinical Trial

Basic information
Public title	Comparative Efficacy and Safety of Immunotherapeutic Regimens with PD-1/PD-L1 Inhibitors for Pre-viously Untreated Extensive-Stage Small-Cell Lung Cancer: A Systematic Review and Network Me-ta-analysis
Acronym	Immunotherapeutic Regimens with PD-1/PD-L1 Inhibitors for Pre-viously Untreated Extensive-Stage Small-Cell Lung Cancer
Scientific Title	Comparative Efficacy and Safety of Immunotherapeutic Regimens with PD-1/PD-L1 Inhibitors for Pre-viously Untreated Extensive-Stage Small-Cell Lung Cancer: A Systematic Review and Network Me-ta-analysis
Scientific Title:Acronym	Immunotherapeutic Regimens with PD-1/PD-L1 Inhibitors for Pre-viously Untreated Extensive-Stage Small-Cell Lung Cancer
Region	Japan

Condition
Condition	Extensive stage small cell lung cancer
Classification by specialty	Medicine in general Pneumology Hematology and clinical oncology
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	To compare the efficacy and safety of immune checkpoint inhibitors and platinum-irinotecan combination therapy for extensive stage small cell lung cancer, and to compare the ICI-containing immunotherapeutic regimens with each other.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	overall survival
Key secondary outcomes	progression free survival Incidence of Grade 3 or higher any adverse events Incidence of Grade 3 or higher neutropenia, anemia, and thrombocytopenia

Base
Study type	Others,meta-analysis etc

Study design
Basic design
Randomization
Randomization unit
Blinding
Control
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
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

Eligibility
Age-lower limit	18 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	Patients with cytologically or histologically confirmed advanced small cell lung cancer. Performance status 0 to 2 Not received previous systemic anti-cancer treatment.
Key exclusion criteria	non-small cell lung cancer patients Poor performance status (3 or more) Patients previously treated with systemic anticancer therapy
Target sample size	2000

Research contact person
Name of lead principal investigator	1st name Koichi Middle name Last name Ando
Organization	Showa University
Division name	Department of Medicine, Division of Respiratory Medicine and Allergology,
Zip code	142-8666
Address	1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan
TEL	+81-3-3784-8532
Email	koichi-a@med.showa-u.ac.jp

Public contact
Name of contact person	1st name Koichi Middle name Last name Ando
Organization	Showa University School of Medicine
Division name	Department of Medicine, Division of Respiratory Medicine and Allergology,
Zip code	1428666
Address	1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan
TEL	+81-3-3784-8532
Homepage URL
Email	koichi-a@med.showa-u.ac.jp

Sponsor
Institute	Showa University
Institute
Department

Funding Source
Organization	Showa University
Organization
Division
Category of Funding Organization	Other
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization	Showa University
Address	1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan
Tel	+81-3-3784-8532
Email	koichi-a@med.showa-u.ac.jp

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2020 Year 09 Month 07 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled	3879
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

Progress
Recruitment status	Completed
Date of protocol fixation	2020 Year 09 Month 01 Day
Date of IRB	2020 Year 09 Month 01 Day
Anticipated trial start date	2020 Year 09 Month 01 Day
Last follow-up date	2020 Year 12 Month 31 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other

Other related information

We aimed to perform a network meta-analysis of relevant phase 3 trials to compare and rank the six treatment arms of pembrolizumab added on platinum plus etoposide, durvalumab added on platinum plus etoposide, atezolizumab added on platinum plus etoposide, platinum plus amrubicin, platinum plus irinotecan, and platinum plus etoposide using a Bayesian approach. The primary efficacy and safety endpoints were overall survival and incidence of grade 3 or more of adverse events, respectively. The surface under the cumulative ranking curve values for efficacy and safety outcomes were assessed to rank each treatment group. No significant differences in overall survival were observed between the pembrolizumab added on platinum plus etoposide and platinum plus irinotecan; durvalumab added on platinum plus etoposide and platinum plus irinotecan; and atezolizumab added on platinum plus etoposide and platinum plus irinotecan groups. Overall survival was the highest for atezolizumab added on platinum plus etoposide, followed by durvalumab added on platinum plus etoposide, pembrolizumab added on platinum plus etoposide, platinum plus irinotecan, platinum plus amrubicin, and platinum plus etoposide. The incidence of grade 3 or more of adverse events was significantly higher in the pembrolizumab added on platinum plus etoposide and atezolizumab added on platinum plus etoposide groups than in the platinum plus irinotecan group. The surface under the cumulative ranking curve values for grade 3 or more of adverse events indicated that IP was the safest, followed by durvalumab added on platinum plus etoposide, platinum plus etoposide, atezolizumab added on platinum plus etoposide, and pembrolizumab added on platinum plus etoposide. These findings provide important insights for clinicians to better select treatment strategies for extensive-stage small-cell lung cancer.

Management information
Registered date	2020 Year 09 Month 06 Day
Last modified on	2021 Year 01 Month 08 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000047602