Dual Checkpoint Inhibition With or Without Chemotherapy in Metastatic NSCLC: A Reconstructed Individual Patient Data Meta-Analysis.
6 affiliations
- 1Division of Hematology & Medical Oncology, Mayo Clinic Arizona, Phoenix, Arizona.
- 2Faculty of Medicine, Federal University of São João del Rei, Divinópolis, Brazil.
- 3Institute of Medical Assistance to the State Public Servant, São Paulo, Brazil.
- 4Faculty of Medicine, Dhaka Medical College and Hospital, Dhaka, Bangladesh.
- 5Department of Medical Oncology, BC Cancer - Abbotsford, Abbotsford, BC, Canada.
- 6Faculty of Medicine, Centro Universitário Faculdade de Medicina do ABC, Santo André, Brazil.
Abstract
Introduction
Dual immune checkpoint inhibition (DICI) is an established first-line treatment for metastatic NSCLC. Whether the addition of chemotherapy provides an incremental survival benefit beyond DICI alone remains unclear.Methods
We performed a systematic review and reconstructed individual patient data meta-analysis of trials evaluating first-line DICI and DICI plus chemotherapy (DICI-CT) in metastatic NSCLC. Data were reconstructed from Kaplan-Meier curves. Overall survival (OS) and progression-free survival were analyzed using Cox proportional hazards and time-varying models. Prespecified subgroup analyses were conducted according to PD-L1 expression, histology, and STK11 or KEAP1 mutational status.Results
Four trials comprising 1654 patients were included (699 receiving DICI-CT and 955 receiving DICI). Median OS was similar between the groups (15.4 versus 15.0 mo, hazard ratio = 0.93, 95% confidence interval: 0.81-1.08). Proportional hazards assumptions were violated, and time-varying analyses suggested modest late survival differences favoring DICI, with higher 5-year OS (19.4% versus 17.1%) and progression-free survival (10.5% versus 8.2%). In STK11-mutated tumors, DICI-CT was associated with a limited early survival benefit that was not sustained over time. No clear differences were observed in KEAP1-mutated tumors.Conclusions
The addition of chemotherapy to DICI was not associated with improved survival in an unselected population of patients with metastatic NSCLC. These findings support an individualized approach to the use of chemotherapy in combination with DICI.
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BibTeX
@article{taylor2026dual,
title = {{Dual Checkpoint Inhibition With or Without Chemotherapy in Metastatic NSCLC: A Reconstructed Individual Patient Data Meta-Analysis.}},
author = {Skyler Taylor and Isadora Mamede and Gabriela Gazzoni and Israt Jahan Riya and Ifrat Jahan Piya and Carlos Stecca and Guilherme Lopes and Antonious Hazim and Vinicius Ernani},
journal = {JTO clinical and research reports},
year = {2026},
month = aug,
doi = {10.1016/j.jtocrr.2026.101059},
url = {https://europepmc.org/article/MED/42927193},
note = {CC BY},
}
RIS
TY - JOUR
TI - Dual Checkpoint Inhibition With or Without Chemotherapy in Metastatic NSCLC: A Reconstructed Individual Patient Data Meta-Analysis.
AU - Skyler Taylor
AU - Isadora Mamede
AU - Gabriela Gazzoni
AU - Israt Jahan Riya
AU - Ifrat Jahan Piya
AU - Carlos Stecca
AU - Guilherme Lopes
AU - Antonious Hazim
AU - Vinicius Ernani
PY - 2026
DA - 2026/08/07
JO - JTO clinical and research reports
DO - 10.1016/j.jtocrr.2026.101059
UR - https://europepmc.org/article/MED/42927193
AB - Introduction Dual immune checkpoint inhibition (DICI) is an established first-line treatment for metastatic NSCLC. Whether the addition of chemotherapy provides an incremental survival benefit beyond DICI alone remains unclear.Methods We performed a systematic review and reconstructed individual patient data meta-analysis of trials evaluating first-line DICI and DICI plus chemotherapy (DICI-CT) in metastatic NSCLC. Data were reconstructed from Kaplan-Meier curves. Overall survival (OS) and progression-free survival were analyzed using Cox proportional hazards and time-varying models. Prespecified subgroup analyses were conducted according to PD-L1 expression, histology, and STK11 or KEAP1 mutational status.Results Four trials comprising 1654 patients were included (699 receiving DICI-CT and 955 receiving DICI). Median OS was similar between the groups (15.4 versus 15.0 mo, hazard ratio = 0.93, 95% confidence interval: 0.81-1.08). Proportional hazards assumptions were violated, and time-varying analyses suggested modest late survival differences favoring DICI, with higher 5-year OS (19.4% versus 17.1%) and progression-free survival (10.5% versus 8.2%). In STK11-mutated tumors, DICI-CT was associated with a limited early survival benefit that was not sustained over time. No clear differences were observed in KEAP1-mutated tumors.Conclusions The addition of chemotherapy to DICI was not associated with improved survival in an unselected population of patients with metastatic NSCLC. These findings support an individualized approach to the use of chemotherapy in combination with DICI.
SN - 2666-3643
ER -