Tumor Mutational Burden and Tislelizumab + Chemo in Advanced NSQ-NSCLC

The primary analysis of RATIONALE-304 (NCT03663205) revealed that combining TIS and platinum-based chemotherapy significantly improved clinical outcomes compared to chemotherapy alone in patients with treatment-naïve advanced advanced advanced non-squamous non-small cell lung cancer (NSCLC). The median progression-free survival (PFS) as determined by the independent review committee (IRC) was 9.7 months for the TIS and chemotherapy group, compared to 7.6 months for the chemotherapy-only group (hazard ratio [HR]=0.645, P=0.0044). This study presented the results of biomarker analysis conducted on baseline tissue and blood TMB, referred to as tTMB and bTMB, respectively. The subjects diagnosed with non-squamous non-small cell lung cancer (nsq-NSCLC) were randomized in a 2:1 ratio. They were either administered with TIS, platinum, and pemetrexed, or platinum and pemetrexed. The OncoScreen Plus® method assessed TMB scores on the initial tumor and blood specimens. The assessment was conducted on the Spearman’s rank correlation between tTMB and bTMB. The independent review committee evaluated the primary endpoint of PFS and categorized the subgroups based on TMB status. Stratification factors such as disease stage and programmed death-ligand 1 (PD-L1) expression were used in a Cox proportional hazard model to assess the PFS. Statistical significance was attributed to interaction P-values < 0.05 without accounting for multiplicity adjustment. Of the 325 patients who received treatment in RATIONALE-304, 54.5% or 177 patients without an EGFR sensitizing mutation had assessable tumor mutational burden (tTMB), while 32.9% or 107 patients had assessable blood-based TMB (bTMB). The median tumor mutational burden (TMB) for tissue TMB (tTMB) and blood TMB (bTMB) were 7.2 and 3.1 mutations per megabase (mut/Mb), respectively. A moderate correlation was observed between tissue tumor mutational burden (tTMB) and blood tumor mutational burden (bTMB) with a Pearson correlation coefficient of 0.71 and a p-value of less than 0.001. A prolonged progression-free survival benefit was observed when adding tumor-infiltrating lymphocytes to chemotherapy in patients with high tumor mutational burden status as compared to those with low tumor mutational burden status, as shown in the table. The interaction analysis revealed that both tTMB and bTMB did not significantly distinguish the PFS benefit specific to treatment (interaction P-values > 0.05).In this retrospective analysis, the association between tTMB and bTMB and PFS benefit was insignificant. This suggests that the clinical usefulness of tTMB and bTMB is limited in the context of TIS + chemo as the primary treatment for advanced nsq-NSCLC.

Source:https://www.abstractsonline.com/pp8/#!/10517/presentation/19967

Clinical Trail:https://clinicaltrials.gov/ct2/show/NCT03663205

Shun Lu, Meili Sun, Yunpeng Liu, Yanping Hu, Yanyan Xie, Zhehai Wang, Dong Wang, Zhenzhou Yang, Liang Liang, Yi Huo, Yun Zhang, Ruiqi Huang, Yang Shi, Zhirong Shen, Yan Yu/RATIONALE-304: The association of tumor mutational burden (TMB) with clinical outcomes of tislelizumab (TIS) + chemotherapy (chemo) versus chemo alone as first-line treatment for advanced non-squamous non-small cell lung cancer (nsq-NSCLC)/(2020). Abstractsonline.com. https://www.abstractsonline.com/pp8/#

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