Statins improve survival in patients previously treated with nivolumab for advanced non‑small cell lung cancer: An observational study

Abstract

There are a number of suggested predictive factors of nivolumab for non-small cell lung cancer (NSCLC), however, there is not enough evidence to determine a single factor that can predict the efficacy of nivolumab. As the progress of biomarkers for cancer treatment is improving, it has been speculated that certain clinical factors serve an important role when predicting the outcome of chemotherapy. A total of 67 patients treated with nivolumab for NSCLC from 2016-2017 were prospectively investigated. Age, sex, the Eastern Cooperative Oncology Group Performance Status, histology, epidermal growth factor receptor (EGFR) mutation, history of chemotherapy, smoking status, use of statins, use of fibrates, use of dipeptidyl peptidase-4 (DPP-4) inhibitors, and use of metformin were examined as clinical factors. Statistical analyses were performed using the Kaplan-Meier method and Cox regression adjusted for risk factors and the tumor response of 67 patients was assessed. The patients had a median age of 67 years (range, 36-87 years), and 46 males and 21 females were enrolled; performance status 0/1 was 59. Cases were categorized as adenocarcinoma (n=41), squamous cell carcinoma (n=17) and other (n=9). A total of 13 patients (19.4%) had EGFR mutations. These clinical factors were not statistically significant in overall survival (OS). Clinical laboratory findings, complications and use of medical agents including antidiabetes mellitus or lipidemia were also analyzed. Statins exhibited statistical significance for response (P= 0.02). Time-to-treatment failure (TTF) in statin-use group was not reached [95% confidence interval (CI): 1.9-not reached] and was 4.0 months (95% CI: 2.0-5.4) in the non-statin group (P=0.039). The median OS in statin-use group was not reached (95% CI: 8.7-not reached) and was 16.5 months (95% CI: 7.5-not reached) in the non-statin group (P= 0.058). NSCLC patients previously treated with nivolumab who were administered statins exhibited an increased response rate and longer TTF. This response was not statistically significant in OS.

Baseline Serum Cholesterol Levels Predict the Response of Patients with Advanced Non-Small Cell Lung Cancer to Immune Checkpoint Inhibitor-Based Treatment

“…We also observed that statin use led to longer PFS and better ORR in the cohort, consistent with earlier research. 15 However, our study has some limitations. First, the retrospective design and small sample size may not get a definitive conclusion, and second, we did not analyze outcomes using different ICI drugs.…”

“…We also observed that statin use led to longer PFS and better ORR in the cohort, consistent with earlier research. 15 …”

“…12,13 Retrospective studies revealed that high serum cholesterol offers positive prognostic value in some types of cancers, including NSCLC, treated with ICIs, 14 and statins have been observed to stimulate immune responses and synergize with anti-PD-1 antibodies in NSCLC. 15 This study compared clinical outcomes with different levels of serum cholesterol and identified high baseline serum cholesterol levels as being associated with the benefits of ICI-based treatments for NSCLC patients.…”

“… 12 , 13 Retrospective studies revealed that high serum cholesterol offers positive prognostic value in some types of cancers, including NSCLC, treated with ICIs, 14 and statins have been observed to stimulate immune responses and synergize with anti-PD-1 antibodies in NSCLC. 15 …”

The role of statins in lung cancer

“…In a study by Omori et al on patients with NSCLC, the results demonstrated that the use of statins with nivolumab improved the treatment of patients when compared to those who were not treated with statins [105].…”