Abstract 620: Associations of genomic alteration, tumor mutational burden with PD-L1 expression and response to immune checkpoint inhibitors in Chinese lung patients
Authors: Hu Jing , Li Bixun , Zou Bing , Wang Senming , Qiu Ye , Yan Maolin , Zeng Zhiming , Yang Han , Guan Yan , Zhang Lei , Chen Wei , Zhang Yuan , Mei Lei , Dong Xiaowei , Yao Ming , Wang Kai 
Published: August 2018

Background: For advanced or metastatic lung cancer patients (pts) in the absence of actionable genetic alterations, whose disease progressed after chemotherapy, the effective treatment options are limited. Recently, PD-1/PD-L1 inhibitors have demonstrated improved survival in advanced lung cancer. However, sufficient evidence is still lacking in Chinese lung cancer pts.

Methods: Twenty lung cancer pts including 12 adenocarcinomas and 5 squamous cell carcinomas who received anti-PD-1/PD-L1 treatments as first- to fourth-line therapy were retrospectively reviewed. The majority of the pts were stage IV (17 pts). PD-L1 expression was analyzed by immunohistochemical staining. Genomic alterations were detected by using a next-generation sequencing (NGS) assay targeting 450 cancer genes. Tumor mutational burden (TMB) and microsatellite instability (MSI) status were acquired by NGS algorithm.

Results: The median age of the 20 pts was 57 years (range: 36-69) and male vs. female was 3. The median time from date of diagnosis to the date of the first anti-PD-1/PD-L1 treatment was 9.5 months (range: 1-69 months). The overall response rate was 89%, including 8 partial response (PR), 9 stable disease (SD) and 2 progressive disease (PD), and the median PFS (mPFS) was not reached (NR) (range: 0.5-NR). Seven pts had one or more targetable oncogenic mutations including EGFR L858R (2) and amplification, PIK3CA (1), BRAF, ERBB2, PTEN, and ROS1 fusion. The median TMB value of the 20 pts was 11 muts/Mb (range: 2.4-38 muts/Mb). 45% of the pts had TMB greater than 20 muts/Mb, and 60% had TMB greater than 10 muts/Mb. Among the 9 pts who had the TMB greater than 20 muts/Mb, 5 pts achieved PR, 4 achieved SD, mPFS was not reached. Also, 5 pts including 2 PR and 3 SD were identified as MSI-high. In the PD-L1 positive subgroup (N=11), 5 pts achieved PR, 5 achieved SD and 1 had a PD. Furthermore, we found 5 pts with NFE2L2 mutations including 2 adenocarcinomas and 3 squamous cell carcinomas, associated with high TMB values (&gt;20 muts/Mb) and PD-L1 positivity; all 5 pts had response to anti-PD-1/PD-L1 treatment, which include 3 PR and 2 SD with mPFS not reached (range: 6-NR).

Conclusion: Our preliminary results based on a small number of pts showed a significant association between high TMB values and response of immune checkpoint inhibitors in Chinese lung cancer pts, and a strong correlation between high TMB values and high PD-L1 expression. We also reported that NFE2L2 mutation was tightly associated with high TMB value (P=0.011) and PD-L1 positivity (P=0.038), which may serve as a new predictive biomarker for advanced or metastatic lung cancer pts receiving anti-PD-1/PD-L1 treatments. Further larger cohort study is warranted.

Citation Format: Jing Hu, Bixun Li, Bing Zou, Senming Wang, Ye Qiu, Maolin Yan, Zhiming Zeng, Han Yang, Yan Guan, Lei Zhang, Wei Chen, Yuan Zhang, Lei Mei, Xiaowei Dong, Ming Yao, Kai Wang. Associations of genomic alteration, tumor mutational burden with PD-L1 expression and response to immune checkpoint inhibitors in Chinese lung patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 620.