Abstract 3548: Loss of heterozygosity (LOH) as a candidate biomarker of PARP inhibitor sensitivity in Chinese solid tumor patients
Authors: Hu Jinwei , Zhang Shuirong , You Kai , Chen Lijuan , Zhang Peng , Shi Junping , Yao Ming , Wang Mo , Wang Kai 
Published: September 2020

Background: Poly (ADP-ribose) polymerase (PARP) plays a vital role in the repair of single-strand DNA breaks through the base excision repair pathway. Several PARP inhibitor approved for advanced BRCA-mutated (BRCAm) ovarian cancer. PARP inhibitors may benefit patients whose tumors are dysfunctional in DNA repair mechanisms unrelated to BRCA1/2. Here we descript the clinical application of LOH score as a candidate biomarker to predicate therapeutic response of PARP inhibitor in Chinese solid tumor patients.

Methods: Formalin fixed paraffin embedded (FFPE) samples of 16 Chinese solid tumor patients were collected for next-generation sequencing (NGS) based 450 genes panel assay. Genomic alterations including single base substitution, short and long insertions/deletions, copy number variations, gene fusions and rearrangement were assessed. Loss of heterozygosity (LOH) status, Microsatellite stable (MSS) status and TMB (tumor mutational burden) were also acquired by an NGS algorithm.

Results: There are 16 patients were analyzed in this retrospective study that most patients having advanced disease stage, Including 9 males and 7 females. The median age is 64 (range, 40-72) years old. The tumor type of these patients including Hepatocellular carcinoma (N=3), Cholangiocarcinoma (N=7), Breast cancer (N=2), Prostate cancer (N=2), Lymphoepithelioma like carcinoma (N=1) and Gallbladder adenocarcinoma (N=1). All 16 patients were treated with PARP inhibitor (Olaparib) including 14 patients harboring BRCA1/2 mutation. 15 patients were evaluable, OS (overall survival) time was calculated until abstract publish. 1 patients achieved complete response (CR), 4 patients achieved partial response (PR), 9 had stable disease (SD) and 1 had progressive disease (PD). Two patients with BRCA wild type achieved SD and the OS time was 13 and 37 months, respectively. LOH status was evaluated all tumors, 25% (4/16) of patients would be considered as having high LOH (LOH-H), including 2 patients without BRCA mutation. 75% (12/16) patients considered as having low LOH (LOH-L). LOH-high group has a longer OS time (P=0.056), median OS time of LOH-H group (N=4) is 25 month (range, 4-42) and LOH-L group (N=11) is 6 month (range, 2-23). Also we explored the association between TMB and OS, identified TMB-H patients (N=6) morel likely has a longer OS (median OS, 11.5 VS 5 month, P=0.017).

Conclusion: In patients with advanced solid cancer, High LOH status was associated with good therapeutic response of PARP inhibitor. LOH status may become a potential indicator for the treatment of PARP inhibitors. Due to the limitations of the number and clinical baseline of patients, the results may require further research and validation.

Citation Format: Jinwei Hu, Shuirong Zhang, Kai You, Lijuan Chen, Peng Zhang, Junping Shi, Ming Yao, Mo Wang, Kai Wang. Loss of heterozygosity (LOH) as a candidate biomarker of PARP inhibitor sensitivity in Chinese solid tumor patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3548.