Durable immunotherapeutic response in molecularly complex pulmonary adenosquamous carcinoma: case report and literature review

Durable immunotherapeutic response in molecularly complex pulmonary adenosquamous carcinoma: case report and literature review

Pulmonary adenosquamous carcinoma (ASC) is a rare and aggressive subtype of non-small cell lung cancer (NSCLC) with poorly defined molecular characteristics and therapeutic strategies. We present a 63-year-old male patient with stage IVa (cT4N3M1b) lung ASC. Next-generation sequencing (NGS) revealed...

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Bibliographic Details
Main Authors: Jun Zhu, Xin Xun, Jiayun Liu, Bin Su, Yi Li, Hong Chen, Meijin Huang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Immunology
Subjects:
non-small cell lung cancer (NSCLC)
lung adenosquamous carcinoma
immune checkpoint inhibitors (ICIs)
immunotherapy
gene mutation
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1614283/full
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Summary:Pulmonary adenosquamous carcinoma (ASC) is a rare and aggressive subtype of non-small cell lung cancer (NSCLC) with poorly defined molecular characteristics and therapeutic strategies. We present a 63-year-old male patient with stage IVa (cT4N3M1b) lung ASC. Next-generation sequencing (NGS) revealed co-occurring mutations in KRAS G12C, BRAF (non-V600E), PIK3CA, and FLT1. Biomarker analysis showed: PD-L1 expression of 18.11% (Tumor Proportion Score, TPS), a tumor mutation burden (TMB) of 3.7 mutations per megabase (mut/Mb), and microsatellite instability (MSI) classified as low (MSI-L) with an instability rate of 35.29%. As first-line treatment, the patient received six cycles of tislelizumab (a PD-1 inhibitor) combined with chemotherapy, followed by tislelizumab maintenance therapy for two years. The patient maintained sustained complete response (CR) with progression-free survival (PFS) reaching 46.5 months, significantly exceeding the typical median PFS of 8-12 months in advanced NSCLC populations. To our knowledge, this presents the first reported case of advanced pulmonary ASC harboring co-occurring driver mutations that demonstrated a remarkable response to immune checkpoint inhibitor (ICI) therapy. Our case highlights the critical role of comprehensive molecular profiling and rational combination strategies in managing rare lung cancer subtypes, establishing a potential treatment paradigm for genomically similar cases.
ISSN:1664-3224

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