On-treatment blood TMB as predictors for camrelizumab plus chemotherapy in advanced lung squamous cell carcinoma: biomarker analysis of a phase III trial

BACKGROUND: Camrelizumab plus chemotherapy significantly prolonged progression-free survival (PFS) and overall survival (OS) compared to chemotherapy alone as first-line treatment in advanced lung squamous cell carcinoma (LUSC) in the phase III trial (CameL-sq), which has become an option of standar...

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Detalles Bibliográficos
Autores principales: Jiang, Tao, Chen, Jianhua, Xu, Xingxiang, Cheng, Ying, Chen, Gongyan, Pan, Yueyin, Fang, Yong, Wang, Qiming, Huang, Yunchao, Yao, Wenxiu, Wang, Rui, Li, Xingya, Zhang, Wei, Zhang, Yanjun, Hu, Sheng, Guo, Renhua, Shi, Jianhua, Wang, Zhiwu, Cao, Peiguo, Wang, Donglin, Fang, Jian, Luo, Hui, Geng, Yi, Xing, Chunyan, Lv, Dongqing, Zhang, Yiping, Yu, Junyan, Cang, Shundong, Zhang, Yaxi, Zhang, Jiao, Yang, Zeyu, Shi, Wei, Zou, Jianjun, Zhou, Caicun, Ren, Shengxiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Research
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8722280/
https://www.ncbi.nlm.nih.gov/pubmed/34980131
http://dx.doi.org/10.1186/s12943-021-01479-4
Descripción
Sumario:BACKGROUND: Camrelizumab plus chemotherapy significantly prolonged progression-free survival (PFS) and overall survival (OS) compared to chemotherapy alone as first-line treatment in advanced lung squamous cell carcinoma (LUSC) in the phase III trial (CameL-sq), which has become an option of standard-of-cares for Chinese patients with advanced LUSC. However, the predictive biomarkers remain unknown. METHODS: Tumor tissue samples at baseline, and peripheral blood samples at baseline (pretreatment) and after two cycles of treatment (on-treatment) were prospectively collected from 270 LUSC patients from the CameL-sq study. Blood tumor mutation burden (bTMB) and its dynamics were analyzed to explore their predictive values. RESULTS: Pretreatment bTMB was not associated with objective response, PFS and OS in camrelizumab or placebo plus chemotherapy groups. Low on-treatment bTMB was associated with significantly better objective response (73.8% vs 27.8%, P < 0.001), PFS (median, 9.1 vs 4.1 months; P < 0.001) and OS (median, not reached vs 8.0 months; P < 0.001) in camrelizumab plus chemotherapy group whereas it did not correlate with objective response and PFS in chemotherapy alone group. Importantly, on-treatment bTMB level could discriminate patients of initially radiological stable disease who would long-term benefit from camrelizumab plus chemotherapy (low vs high, median OS, 18.2 vs 7.8 months; P = 0.001). Combing on-treatment bTMB and its dynamics improved the ability for predicting the efficacy of camrelizumab plus chemotherapy. CONCLUSION: On-treatment bTMB together with its dynamics could serve as a predictive biomarker for camrelizumab plus chemotherapy in patients with advanced LUSC. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03668496. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12943-021-01479-4.

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