Homologous recombination deficiency status predicts response to immunotherapy‐based treatment in non‐small cell lung cancer patients

Abstract

Abstract Background Homologous recombination deficiency (HRD) is a biomarker that predicts response to ovarian cancer treatment with poly (ADP‐ribose) polymerase (PARP) inhibitors or breast cancer treatment with first‐line platinum‐based chemotherapy. However, there are few studies on the prognosis of lung cancer patients treated with immune checkpoint inhibitor (ICI) therapy using HRD as a biomarker. Methods We studied the relationship between HRD status and the effectiveness of first‐line ICI‐based therapy in EGFR/ALK wild‐type metastatic non‐small cell lung cancer patients (NSCLC) patients. Results This study included 22 treatment naïve NSCLC patients. The HRD score ranged from −26.37 to 92.34, with an average of 24.57. Based on analysis of the progression‐free survival (PFS) data from the included NSCLC patients, threshold traversal was carried out. HRD (+) was defined as an HRD score of 31 or higher. Kaplan–Meier PFS survival analysis showed prolonged median PFS (mPFS) in NSCLC patients with HRD (+) versus HRD (−) (N/A vs. 7.0 ms, log‐rank p = 0.029; HR 0.20, 95% CI: 0.04–0.96, likelihood‐ratio p = 0.03). In patients with PD‐L1 TPS ≥50% and HRD score ≥31 (co‐status high), the mPFS was temporarily not reached during the follow‐up period. In patients with PD‐L1 TPS <1% and HRD score <31, the mPFS was 3 ms. Cox regression analysis showed that the hazard ratio of the co‐status was 0.14 (95% CI: 0.04–0.54), which was a good prognostic factor, and the prognostic effect of co‐status was better than that of HRD score alone. Conclusion The HRD status can be identified as an independent significance in NSCLC patients treated with first‐line ICI‐based therapy.

Keywords

• HRD
• immunotherapy
• non‐small cell lung cancer