Potential Immune Microenvironment Biomarkers in SCLC: J-TAIL-2 Observational Study

IF 3.6 Q2 ONCOLOGY

JTO Clinical and Research Reports Pub Date : 2026-03-01 Epub Date: 2025-10-29 DOI:10.1016/j.jtocrr.2025.100926

Masayuki Shirasawa MD, PhD , Makoto Nishio MD, PhD , Kadoaki Ohashi MD, PhD , Atsushi Osoegawa MD, PhD , Eiki Kikuchi MD, PhD , Hideharu Kimura MD, PhD , Yasushi Goto MD, PhD , Junichi Shimizu MD, PhD , Eisaku Miyauchi MD, PhD , Hiroshige Yoshioka MD, PhD , Ichiro Yoshino MD, PhD , Toshihiro Misumi PhD , Yasushi Yatabe MD, PhD , Tatsuya Yoshida MD, PhD , Jumpei Kashima MD, PhD , Masahide Oki MD, PhD , Hisao Ashimura MS , Yuki Kobayashi MS , Misa Tanaka MS , Akihiko Gemma MD, PhD

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引用次数: 0

Abstract

Introduction

Effective predictors of response to atezolizumab plus carboplatin/etoposide (CE) therapy in extensive-stage SCLC (ES-SCLC) remain limited. This exploratory analysis from J-TAIL-2 aimed to identify markers of survival benefit with atezolizumab plus CE therapy in ES-SCLC.

Methods

J-TAIL-2 (ClinicalTrials.gov ID, NCT04501497) was a multicenter observational study that enrolled patients receiving atezolizumab plus CE (ES-SCLC cohort) in clinical practice in Japan per local label and treatment guidelines. In this exploratory analysis, the association of CD8+ tumor-infiltrating lymphocyte (TIL) density and SCLC subtypes (SCLC-A [ASCL1 dominant], SCLC-N [NEUROD1 dominant], SCLC-P [ASCL1/NEUROD1 double-negative with POU2F3 expression], and SCLC-O [ASCL1/NEUROD1 double-negative not otherwise specified]) with overall survival (OS) and progression-free survival (PFS) was evaluated. SCLC subtyping was performed by immunohistochemistry.

Results

SCLC samples (n = 100; data cutoff, February 3, 2023) were categorized as SCLC-A (73%), SCLC-N (16%), SCLC-P (8%), and SCLC-O (3%). Among 96 patients who received first-line atezolizumab plus CE, median age was 72 (range, 39–87) years and 81% were male. Furthermore, 56 patients were classified into the CD8+ TIL-high subgroup and 40 into the TIL-low subgroup. Median (m)PFS with atezolizumab plus CE was 6.1 months (95% confidence interval [CI]: 4.5–7.5) in the TIL-high versus 4.4 months (95% CI: 4.0–5.1) in the TIL-low subgroup (p = 0.01); mOS was 18.4 (95% CI: 11.8–not estimable) versus 10.8 months (95% CI: 7.7–16.2; p = 0.04). mOS and mPFS were not significantly different between SCLC subtypes but were numerically shorter in the SCLC-N group.

Conclusions

CD8+ TIL density is a potential biomarker of clinical benefit in ES-SCLC and may facilitate patient selection for atezolizumab combination therapy.

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SCLC中潜在的免疫微环境生物标志物：J-TAIL-2观察研究。

导语：atezolizumab联合卡铂/依托泊苷（CE）治疗大分期SCLC （ES-SCLC）的有效预测指标仍然有限。这项来自J-TAIL-2的探索性分析旨在确定atezolizumab加CE治疗ES-SCLC的生存获益标志物。J-TAIL-2 （ClinicalTrials.gov ID, NCT04501497）是一项多中心观察性研究，根据日本当地标签和治疗指南，在临床实践中招募了接受atezolizumab加CE （ES-SCLC队列）的患者。在这项探索性分析中，我们评估了CD8+肿瘤浸润淋巴细胞（TIL）密度和SCLC亚型（SCLC- a [ASCL1显性]、SCLC- n [NEUROD1显性]、SCLC- p [ASCL1/NEUROD1双阴性伴POU2F3表达]和SCLC- o [ASCL1/NEUROD1双阴性，另有说明]）与总生存期（OS）和无进展生存期（PFS）的关系。免疫组织化学进行SCLC分型。结果：SCLC样本（n = 100，数据截止日期为2023年2月3日）分为SCLC- a（73%）、SCLC- n（16%）、SCLC- p（8%）和SCLC- o（3%）。在96例接受一线atezolizumab + CE治疗的患者中，中位年龄为72岁（范围39-87），81%为男性。CD8+ til高亚组56例，til低亚组40例。在til -高亚组中，atezolizumab加CE的中位PFS (m)为6.1个月（95%可信区间[CI]: 4.5-7.5），而在til -低亚组中，PFS为4.4个月（95% CI: 4.0-5.1）（p = 0.01）；mOS为18.4个月（95% CI: 11.8-不可估计），而10.8个月（95% CI: 7.7-16.2; p = 0.04）。不同SCLC亚型间的mOS和mPFS无显著差异，但SCLC- n组的mOS和mPFS数值较短。结论：CD8+ TIL密度是ES-SCLC临床获益的潜在生物标志物，可能有助于患者选择atezolizumab联合治疗。

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