Clinical and Molecular Characterization of Long-Term Survivors With Extensive-Stage Small Cell Lung Cancer Treated With First-Line Atezolizumab Plus Carboplatin and Etoposide

Authors

Stephen V Liu
Tony S K Mok
Barzin Y Nabet
Aaron S Mansfield
Richard De Boer
György Losonczy
Shunichi Sugawara
Rafal Dziadziuszko
Maciej Krzakowski
Alexey Smolin
Maximilian J Hochmair
Marina C Garassino
Carl M Gay
John V Heymach
Lauren A Byers
Sivuonthanh Lam
Andrés Cardona
Stefanie Morris
Leah Adler
David S Shames
Martin Reck

Language

English

Publication Date

12-1-2023

Journal

Lung Cancer

DOI

10.1016/j.lungcan.2023.107418

PMID

37931445

Abstract

Objectives: In the Phase I/III IMpower133 study, first-line atezolizumab plus carboplatin and etoposide (CP/ET) treatment for extensive-stage small cell lung cancer (ES-SCLC) significantly improved overall survival (OS) and progression-free survival versus placebo plus CP/ET. We explored patient and disease characteristics associated with long-term survival in IMpower133, and associations of differential gene expression and SCLC-A (ASCL1-driven), SCLC-N (NEUROD1-driven), SCLC-P (POU2F3-driven), and SCLC-inflamed (SCLC-I) transcriptional subtypes with long-term survival.

Materials and methods: Patients with previously untreated ES-SCLC were randomized 1:1 to four 21-day cycles of CP/ET with atezolizumab or placebo. Long-term survivors (LTS) were defined as patients who lived ≥ 18 months post randomization. A generalized linear model was used to evaluate the odds of living ≥ 18 months. Differential gene expression was analyzed using RNA-sequencing data in LTS and non-LTS. OS was assessed by T-effector and B-cell gene signature expression. Distribution of SCLC transcriptional subtypes was assessed in LTS and non-LTS.

Results: More LTS were in the atezolizumab arm (34%) than in the placebo arm (20%). The odds ratio for living ≥ 18 months in the atezolizumab arm versus the placebo arm was 2.1 (P < 0.03). Enhanced immune-related signaling was seen in LTS in both arms. Exploratory OS analyses showed atezolizumab treatment benefit versus placebo across T-effector and B-cell gene signature expression subgroups. A higher proportion of LTS than non-LTS in both arms had the SCLC-I subtype; this difference was particularly pronounced in the atezolizumab arm.

Conclusion: These exploratory analyses suggest that long-term survival is more likely with atezolizumab than placebo in ES-SCLC, confirming the treatment benefit of the IMpower133 regimen.

Clinicaltrial: gov Identifier: NCT02763579.

Keywords

Humans, Small Cell Lung Carcinoma, Carboplatin, Etoposide, Lung Neoplasms, Survivors, Antineoplastic Combined Chemotherapy Protocols, Antibodies, Monoclonal, Humanized, (maximum 6): Small cell lung carcinoma, Atezolizumab, Carboplatin, Clinical trial IMpower133, Etoposide, Gene expression profiling, Immune checkpoint inhibitors, RNA Sequence analysis

Published Open-Access

yes

Recommended Citation

Liu, Stephen V; Mok, Tony S K; Nabet, Barzin Y; et al., "Clinical and Molecular Characterization of Long-Term Survivors With Extensive-Stage Small Cell Lung Cancer Treated With First-Line Atezolizumab Plus Carboplatin and Etoposide" (2023). Faculty, Staff and Student Publications. 5409.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5409