Tumor mutational burden and efficacy of chemotherapy in lung cancer
-
Juan Song [1] ; Yu Yan [1] ; Cuicui Chen [1] ; Jiamin Li [1] ; Ning Ding [1] ; Nuo Xu [1] ; Hairong Bao [2] ; Xin Zhang [1] ; Qunying Hong [1] ; Jian Zhou [1] ; Yang W. Shao [2] ; Yuanlin Song [1] ; Lin Tong [1] ; Jie Hu [1]
-
[1] Zhongshan Hospital
Zhongshan Hospital
China
-
[2] Nanjing Geneseeq Technology Inc, Nanjing, 210032, Jiangsu, China
-
- Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 25, Nº. 1 (January), 2023, págs. 173-184
- Idioma: inglés
- Texto completo no disponible (Saber más ...)
-
Resumen
Purpose TMB is one of the potent biomarkers of response to immune checkpoint blockade. The association between TMB and efficacy of chemotherapy in advanced lung cancer has not been comprehensively explored.
Methods Ninety lung cancer patients receiving first-line chemotherapy with large panel next-generation sequencing data of pre-treatment tumor tissue were identified. The effect of TMB on PFS of chemotherapy were evaluated in univariate and multivariate analyses.
Results The median TMB level of lung cancer patients enrolled in this study was 9.4 mutations/Mb, with TMB levels in smokers significantly higher than those in non-smokers. All patients were divided into high TMB and low TMB groups with the cutoff of the median TMB. The patients with low TMB had longer PFS of first-line chemotherapy (median PFS 9.77 vs 6.33 months, HR = 0.523, 95% CI 0.32–0.852, log-rank P = 0.009). Subgroup analysis showed that PFS of chemotherapy favored low TMB than high TMB among subgroups of male, age < 60, NSCLC, adenocarcinoma, stage IV, ECOG PS 0, driver mutation positive, TP53 wild type and patients not receiving bevacizumab. In multivariate analysis, PFS of chemotherapy remained significantly longer in low TMB group (HR = 0.554, p = 0.036). In those patients received immunotherapy upon unsatisfactory chemotherapy, PFS of immunotherapy was much longer in high TMB group (median PFS 32.88 vs 6.62 months, HR = 0.2426, 95% CI 0.06–0.977, log-rank P = 0.04).
Conclusions TMB level of tumor tissue is a potent biomarker for efficacy of chemotherapy and immunotherapy in lung cancer. It may provide some clues for the decision of treatment strategy.
