Clinical and molecular characterization of long-term survivors with extensive-stage small cell lung cancer treated with first-line atezolizumab plus carboplatin and etoposide
- Author(s)
- Liu, SV; Mok, TSK; Nabet, BY; Mansfield, AS; De Boer, R; Losonczy, G; Sugawara, S; Dziadziuszko, R; Krzakowski, M; Smolin, A; Hochmair, MJ; Garassino, MC; Gay, CM; Heymach, JV; Byers, LA; Lam, S; Cardona, A; Morris, S; Adler, L; Shames, DS; Reck, M;
- Journal Title
- Lung Cancer
- Publication Type
- Research article
- 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.
- Publisher
- Elsevier
- Keywords
- (maximum 6): Small cell lung carcinoma; Atezolizumab; Carboplatin; Clinical trial IMpower133; Etoposide; Gene expression profiling; Immune checkpoint inhibitors; RNA Sequence analysis
- Department(s)
- Medical Oncology
- PubMed ID
- 37931445
- Publisher's Version
- https://doi.org/10.1016/j.lungcan.2023.107418
- Open Access at Publisher's Site
https://doi.org/10.1016/j.lungcan.2023.107418- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-12-05 12:35:29
Last Modified: 2023-12-05 12:50:03