Trends in treatment and survival of stage IV non-squamous NSCLC from 2010 to 2022
5 affiliations
- 1Department of Internal Medicine, Cleveland Clinic, Cleveland, OH USA
- 2Department of Quantitative Health Sciences, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH USA
- 3Department of Pathology and Laboratory Medicine, Cleveland Clinic, Cleveland, OH USA
- 4Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, CA Building, 10201 Carnegie Ave, Cleveland, OH 44106 USA
- 5Center for Immunotherapy and Precision Immuno-Oncology, Cleveland Clinic, Cleveland, OH USA
Abstract
Background: Advances in immunotherapy (IT) and targeted therapy have transformed treatment for stage IV non-squamous non-small cell lung cancer (NS-NSCLC). However, real-world data comparing modern regimens to previous standards remains limited. Herein, we aim to determine whether survival outcomes have improved with contemporary therapies,
Methods: We conducted a retrospective analysis of de novo stage IV NS-NSCLC at diagnosis treated at the Cleveland Clinic, OH, from 1/2010 to 12/2022. Baseline variables, including age, sex, race, performance status, smoking history, PD-L1 testing, and molecular profiling, were collected along with treatment regimens. Treatment responses were assessed. Overall survival (OS) and progression-free survival (PFS) were estimated. Multivariable Cox regression (CPH) was used to adjust for confounding.
Results: We identified 1,518 patients with NS-NSCLC, of which 97% had adenocarcinoma (N = 1,472). Median age was 65 (IQR 58–73); 51% were female, 82% white, and 42% current smokers. Treatments included conventional chemotherapy (CTX) (744, 49%), IT (186, 12%), CTX + IT (318, 21%), and targeted therapy (270, 18%). Common regimens were carboplatin + pemetrexed/paclitaxel (502, 80%) and bevacizumab + carboplatin + pemetrexed/paclitaxel (127, 20%) for CTX, pembrolizumab (167, 89%) for IT, and carboplatin + pemetrexed + pembrolizumab (153, 41%) for chemo-IT. Overall disease control rate was 58% with a median follow-up of 69.7 months. The 2- and 5-year OS were 30% and 12%, respectively. OS improved from 20% (2010–2012) to 38% (2019–2022) (P < 0.05). Modern regimens were associated with a 23% reduced hazard of death (HR 0.77, 95% CI 0.66–0.90, p < 0.001).
Conclusion: Modern regimens were associated with improved survival in stage IV NS-NSCLC, but long-term survival remains poor, underscoring the need for further research.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12885-026-16590-2.
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BibTeX
@article{rehman2026trends,
title = {{Trends in treatment and survival of stage IV non-squamous NSCLC from 2010 to 2022}},
author = {Naveen Rehman and Emily C. Zabor and Aastha Dhakal and Bridget Adcock and Muaz Alsabbagh Alchirazi and Moath Albliwi and Ali Mushtaq and Hadil Zureigat and Monica Lee and Ahmed Nabil Mohamed Hassan and Heya Batah and Preeyal Patel and Meera Patel and Sara Haddad and Scott Robertson and Michael Menefee and Khaled Aref Hassan and Marc A. Shapiro and James Stevenson and Alex A Adjei and Lukas Delasos and Moaath K. Mustafa Ali},
journal = {BMC Cancer},
year = {2026},
month = jul,
doi = {10.1186/s12885-026-16590-2},
url = {https://doi.org/10.1186/s12885-026-16590-2},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Trends in treatment and survival of stage IV non-squamous NSCLC from 2010 to 2022
AU - Naveen Rehman
AU - Emily C. Zabor
AU - Aastha Dhakal
AU - Bridget Adcock
AU - Muaz Alsabbagh Alchirazi
AU - Moath Albliwi
AU - Ali Mushtaq
AU - Hadil Zureigat
AU - Monica Lee
AU - Ahmed Nabil Mohamed Hassan
AU - Heya Batah
AU - Preeyal Patel
AU - Meera Patel
AU - Sara Haddad
AU - Scott Robertson
AU - Michael Menefee
AU - Khaled Aref Hassan
AU - Marc A. Shapiro
AU - James Stevenson
AU - Alex A Adjei
AU - Lukas Delasos
AU - Moaath K. Mustafa Ali
PY - 2026
DA - 2026/07/31
JO - BMC Cancer
DO - 10.1186/s12885-026-16590-2
UR - https://doi.org/10.1186/s12885-026-16590-2
AB - Background: Advances in immunotherapy (IT) and targeted therapy have transformed treatment for stage IV non-squamous non-small cell lung cancer (NS-NSCLC). However, real-world data comparing modern regimens to previous standards remains limited. Herein, we aim to determine whether survival outcomes have improved with contemporary therapies, Methods: We conducted a retrospective analysis of de novo stage IV NS-NSCLC at diagnosis treated at the Cleveland Clinic, OH, from 1/2010 to 12/2022. Baseline variables, including age, sex, race, performance status, smoking history, PD-L1 testing, and molecular profiling, were collected along with treatment regimens. Treatment responses were assessed. Overall survival (OS) and progression-free survival (PFS) were estimated. Multivariable Cox regression (CPH) was used to adjust for confounding. Results: We identified 1,518 patients with NS-NSCLC, of which 97% had adenocarcinoma (N = 1,472). Median age was 65 (IQR 58–73); 51% were female, 82% white, and 42% current smokers. Treatments included conventional chemotherapy (CTX) (744, 49%), IT (186, 12%), CTX + IT (318, 21%), and targeted therapy (270, 18%). Common regimens were carboplatin + pemetrexed/paclitaxel (502, 80%) and bevacizumab + carboplatin + pemetrexed/paclitaxel (127, 20%) for CTX, pembrolizumab (167, 89%) for IT, and carboplatin + pemetrexed + pembrolizumab (153, 41%) for chemo-IT. Overall disease control rate was 58% with a median follow-up of 69.7 months. The 2- and 5-year OS were 30% and 12%, respectively. OS improved from 20% (2010–2012) to 38% (2019–2022) (P < 0.05). Modern regimens were associated with a 23% reduced hazard of death (HR 0.77, 95% CI 0.66–0.90, p < 0.001). Conclusion: Modern regimens were associated with improved survival in stage IV NS-NSCLC, but long-term survival remains poor, underscoring the need for further research. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12885-026-16590-2.
SN - 1471-2407
ER -