Low baseline plasma PCSK9 level is associated with good clinical outcomes of immune checkpoint inhibitors in advanced non-small cell lung cancer

Abstract

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a crucial protein involved in the metabolism of low-density lipoprotein cholesterol. However, the role of plasma PCSK9 in predicting the efficacy of ICIs in advanced non-small cell lung cancer (NSCLC) remains to be clarified.

Methods: We retrospectively reviewed the medical records of NSCLC patients who presented at Shanghai Pulmonary Hospital between April 2019 and June 2020. ELISA was conducted to detect the concentration of PCSK9. Clinical efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1).

Results: A total of 55 patients were enrolled in the study. The median progression-free survival (PFS) following treatment with ICIs in all patients was 9.9 months. The optimal threshold of baseline plasma PCSK9 was 232.2 ng/ml. Patients with low baseline plasma PCSK9 had a longer PFS (NR vs. 7.37 months, p = 0.017, HR = 0.207, 95% CI: 0.086-0.498) and a better response (ORR 71.4% vs. 43.9%, p = 0.075, DCR 100% vs. 80.5%, p = 0.098) to ICIs. Younger patients (≤66 years) with a lower PCSK9 had a significantly longer PFS and higher treatment response than those with a high baseline level of PCSK9 (NR vs. 5.83 months, p = 0.021, HR = 0.134, 95% CI: 0.044-0.409; ORR 66.7% vs. 30.0%, p = 0.106, DCR 100% vs. 75%, p = 0.153). The situation was similar in patients who received first-line therapy (NR vs. 8.97 months, p = 0.022, HR = 0.138, 95% CI: 0.047-0.400; ORR 63.6% vs. 46.4%, p = 0.480, DCR 100% vs. 89.3%, p = 0.545). Multivariate analysis showed that low PCSK9 concentration was independently associated with PFS (p = 0.032, HR = 0.201).

Conclusions: Low baseline plasma PCSK9 level may predict good outcomes in patients with advanced NSCLC treated with ICIs.

Keywords: biomarker; immune checkpoint inhibitors (ICIs); non-small cell lung cancer (NSCLC); proprotein convertase subtilisin/kexin type 9 (PCSK9).