Clinical and molecular characterization of long-term survivors with extensive-stage small cell lung cancer treated with first-line atezolizumab plus carboplatin and etoposide

• Published in: Lung cancer (Amsterdam, Netherlands) Netherlands), 2023-12, Vol.186, p.107418-107418, Article 107418
• Main Authors: Liu, Stephen V, Mok, Tony S K, Nabet, Barzin Y, Mansfield, Aaron S, De Boer, Richard, Losonczy, György, Sugawara, Shunichi, Dziadziuszko, Rafal, Krzakowski, Maciej, Smolin, Alexey, Hochmair, Maximilian J, Garassino, Marina C, Gay, Carl M, Heymach, John V, Byers, Lauren A, Lam, Sivuonthanh, Cardona, Andrés, Morris, Stefanie, Adler, Leah, Shames, David S, Reck, Martin
• Format: Article
• Language: English
• Subjects: Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Carboplatin; Etoposide; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Small Cell Lung Carcinoma - drug therapy; Small Cell Lung Carcinoma - genetics; Survivors
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2023.107418

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. 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. 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