Heterogeneity in advanced pulmonary sarcomatoid carcinoma and its efficacy to immune checkpoint inhibitors

Mengqing Xie; Tianqing Chu; Xiaorong Dong; Huijuan Wang; Qian Chu; Xiuyu Cai; Jialei Wang; Yu Yao; Lin Wu; Feng Ye; Bo Zhu; Caicun Zhou; Chunxia Su

doi:10.1016/j.ejca.2024.114260

Heterogeneity in advanced pulmonary sarcomatoid carcinoma and its efficacy to immune checkpoint inhibitors

Eur J Cancer. 2024 Sep:209:114260. doi: 10.1016/j.ejca.2024.114260. Epub 2024 Aug 2.

Authors

Mengqing Xie¹, Tianqing Chu², Xiaorong Dong³, Huijuan Wang⁴, Qian Chu⁵, Xiuyu Cai⁶, Jialei Wang⁷, Yu Yao⁸, Lin Wu⁹, Feng Ye¹⁰, Bo Zhu¹¹, Caicun Zhou¹, Chunxia Su¹²

Affiliations

¹ Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Tongji University, Shanghai, China.
² Department of Respiratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
³ Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁴ Department of Medical Oncology, Henan Cancer Hospital, Zhengzhou, China.
⁵ Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China.
⁶ Department of General Internal Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, China.
⁷ Department of Thoracic Medical Oncology, Fudan University Shanghai Cancer Center, China.
⁸ Department of Oncology Internal Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'An, China.
⁹ Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, China.
¹⁰ Department of Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, China.
¹¹ Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
¹² Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Tongji University, Shanghai, China. Electronic address: susu_mail@126.com.

PMID: 39111208
DOI: 10.1016/j.ejca.2024.114260

Abstract

Background: Immune checkpoint inhibitors (ICIs) have improved the prognosis of patients with non-small cell lung cancer but rarely been explored in pulmonary sarcomatoid carcinoma (PSC). This multicenter study aimed to evaluate the effectiveness of ICIs for PSC and its underlying mechanism.

Methods: Advanced PSC who received ICIs between August 2018 and May 2022 from 11 centers in China were included. Clinical characteristics and treatment information were collected. Whole-exome sequencing (WES) and whole transcriptome sequencing were conducted on pre-treatment samples to explore the mechanism.

Results: 113 patients with PSC were enrolled, the median PFS for patients receiving ICIs therapy was 8.77 months (95 % confidence interval, 4.21 to 13.32). Combining ICIs with anti-angiogenic agents significantly increased PFS (p = 0.04). Liver metastasis and combination therapy with anti-angiogenic agents were independent risk factors for PFS (Hazard Ratio [HR] = 3.652, p = 0.019 and HR = 0.435, p = 0.017, respectively). WES showed that PSC presented with a TMB of 6.3 mutations per million base pairs. High expression of TNFα signaling and glycolysis related gene showed a better prognosis.

Conclusions: ICIs showed promising benefits for advanced PSC, and the addition of anti-angiogenic therapy might be a more effective treatment strategy for this disease.

Keywords: Anti-angiogenic therapy; Immunotherapy; NSCLC; Rare tumor; Tumor microenvironment.

Publication types

Multicenter Study

MeSH terms

Adult
Aged
Angiogenesis Inhibitors / therapeutic use
Biomarkers, Tumor / genetics
Exome Sequencing
Female
Humans
Immune Checkpoint Inhibitors* / therapeutic use
Lung Neoplasms* / drug therapy
Lung Neoplasms* / genetics
Lung Neoplasms* / pathology
Male
Middle Aged
Mutation
Prognosis

Substances

Immune Checkpoint Inhibitors
Angiogenesis Inhibitors
Biomarkers, Tumor