e21635 Background: DNA damage response and repair (DDR) pathway alteration is known as a predictive biomarker of platinum-based chemotherapy sensitivity in urothelial carcinoma, breast cancer, ovarian cancer, and prostate cancer. However, the predictive value of DDR in patients with non-small cell lung cancer (NSCLC) is still uncertain. This study investigated the DDR mutations (MUT) of NSCLC to identify potential predictive biomarker. Methods: A retrospective analysis of patients with NSCLC was performed. Targeted exon sequencing with the Next Generation Sequencing (NGS) were performed for 298 patients, and they were divided into two groups based on the presence or absence of mutations in 36 DDR genes. Results: 50 patients treated with platinum-based chemotherapy were identified, of which 17 harbored alterations in DDR genes. The median age was 60.5 years (range, 43 to 79 years). A total of 50 patients were evaluated, the objective response rate (ORR) of patients with DDR MUT was 17.6%, ORR 0% for DDR wild-type (WT), and the disease control rate (DCR) was 76.4% for DDR MUT, 48.5% for DDR WT. In terms of survival analysis, patients with DDR MUT had significantly improved median progression-free survival (mPFS) of 9.2 months compared with 4.8 months for DDR WT (Hazard Ratio (HR) = 0.4134, log-rank P = 0.0117). When EGFR and ALK mutations were excluded, there was no significant difference in mPFS between DDR MUT and WT, but DDR MUT has a tendency to be higher than WT (mPFS: 8.0 vs. 4.7 months, HR = 0.5060, log-rank P = 0.1022). Nevertheless, there was no significant difference in the median overall survival (mOS) between two groups (DDR MUT vs. DDR WT: 21.7 vs. 29.4 months, HR = 1.537, log-rank P = 0.3756), even after EGFR and ALK mutations were excluded, no significant difference can also be gained (HR = 1.818, log-rank P = 0.3972). Conclusions: DDR mutations may be a positive predictive biomarker for response to platinum-based chemotherapy in patients with NSCLC.
DNA Damage Response and Repair Pathway Alteration and Its Association With Tumor Mutation Burden and Platinum-Based Chemotherapy in SCLC
