Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Lung cancer (Amsterdam, Netherlands), 2023-12, Vol.186, p.107418-107418, Article 107418

Ort / Verlag

Ireland

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 < 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. 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. gov Identifier: NCT02763579.