KEY TAKEAWAYS
- The Phase III trial (CameL-sq) with Camrelizumab in combination with chemotherapy significantly extends PFS and OS in advanced LUSC.
- Prospective analysis of bTMB and its dynamics in 270 patients with LUSC in CameL-sq trial.
- Pre-treatment bTMB was not correlated with response, PFS, or OS, but low on-treatment bTMB was associated with a better response.
- On-treatment bTMB level can differentiate patients who will benefit from camrelizumab in the long term.
- Integration of on-treatment bTMB and its kinetics may function as a prognostic biomarker for camrelizumab in combination with chemotherapy in advanced LUSC.
- Camrelizumab combined with chemotherapy is now the standard of care for Chinese patients with advanced LUSC
The phase III trial (CameL-sq) has demonstrated that the administration of Camrelizumab in combination with chemotherapy as first-line treatment for advanced lung squamous cell carcinoma (LUSC) significantly extended progression-free survival (PFS) and overall survival (OS) compared to chemotherapy alone. This treatment option has become a standard of care for Chinese patients diagnosed with advanced LUSC. However, the identity of the predictive biomarkers remains undisclosed. Baseline tumor tissue samples and peripheral blood samples were prospectively collected from 270 patients with LUSC in the CameL-sq study. Additionally, peripheral blood samples were collected from patients both before treatment (pretreatment) and after two cycles of treatment (on-treatment). The analysis of blood tumor mutation burden (bTMB) and its dynamics was conducted to investigate their predictive values.
The pre-treatment blood tumor mutational burden (bTMB) did not exhibit any correlation with the objective response (OR), progression-free survival (PFS), and overall survival (OS) in the groups receiving camrelizumab or placebo in combination with chemotherapy. 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. Significantly, the bTMB level during treatment could differentiate patients who initially had radiologically stable disease and would benefit from camrelizumab in combination with chemotherapy in the long term (low vs high, median OS, 18.2 vs 7.8 months; P = 0.001). The integration of on-treatment blood tumor mutational burden (bTMB) and its kinetics has enhanced the prognostic potential of camrelizumab in combination with chemotherapy. Using on-treatment bTMB with its dynamics may function as a prognostic biomarker for camrelizumab in combination with chemotherapy for individuals experiencing advanced LUSC.
Source:https://pubmed.ncbi.nlm.nih.gov/34980131/
Clinical Trail:https://clinicaltrials.gov/ct2/show/NCT03668496
Jiang T, Chen J, Xu X, Cheng Y, Chen G, Pan Y, Fang Y, Wang Q, Huang Y, Yao W, Wang R, Li X, Zhang W, Zhang Y, Hu S, Guo R, Shi J, Wang Z, Cao P, Wang D, Fang J, Luo H, Geng Y, Xing C, Lv D, Zhang Y, Yu J, Cang S, Zhang Y, Zhang J, Yang Z, Shi W, Zou J, Zhou C, Ren S. On-treatment blood TMB as predictors for camrelizumab plus chemotherapy in advanced lung squamous cell carcinoma: biomarker analysis of a phase III trial. Mol Cancer. 2022 Jan 3;21(1):4. doi: 10.1186/s12943-021-01479-4. PMID: 34980131; PMCID: PMC8722280.
