Impact of Hyperglycemia in Patients with Advanced NSCLC with PD-L1 ≥50% Treated with Frontline Pembrolizumab

In patients with curable non–small-cell lung cancer (NSCLC), hyperglycemia is linked to a poor prognosis, but its effect in patients with advanced NSCLC is unknown. Approximately one-third of patients with PD-L1 will proceed to receive pembrolizumab early, and indicators that are able to predict poor outcomes are urgently required.¹ Malignant tumors are frequently complex. Hyperglycemia has been found in epidemiologic studies to increase the prevalence and mortality rate in some cancers and can stimulate tumor cell proliferation, invasion, and migration, as well as induce apoptosis and increase chemoresistance.²

A retrospective study looked at the predictive effects of high fasting plasma glucose (HFG, >7 mmol/L) in a group of patients with stage IV EGFR/ALK-negative NSCLC who received frontline pembrolizumab and had a PD-L1 ≤50%. Progression-free survival (PFS) and overall survival were evaluated.¹

Sixty-six patients were included from August 2017 to June 2020. The median age was 65.1 years (range, 40.4-90.3 years); 75.8% patients were men, and 15.2% had liver metastases at the time of diagnosis. HFG was discovered in 30.3% of patients at the time of diagnosis, despite the fact that only 45.0% of them had previously been diagnosed with type 2 diabetes. There were no differences between HFG and non-HFG groups in terms of gender, smoking history, comorbidities, Eastern Cooperative Oncology Group (ECOG) performance status, tumor histology, or PD-L1 expression. HFG was linked to liver metastases (P = .001) and early progression (P = .003) at 3 months. With a median follow-up of 18 months, median PFS in patients with HFG was substantially lower (2.2 months) compared with non-HFG patients (27.0 months). Median overall survival was significantly shorter in patients with HFG (6.0 months) versus non-HFG (40.7 months). HFG, ECOG performance status, and liver metastases at diagnosis were all linked to a shorter PFS. After correcting for ECOG performance status and the presence of liver metastases, HFG remained an independent prognostic factor for PFS.¹

In this cohort of patients treated with frontline pembrolizumab, baseline HFG was related to poorer PFS and early tumor progression at 3 months. To corroborate this link, prospective studies in larger cohorts of patients with NSCLC treated with immunotherapy are needed.¹ In other studies, diabetes has been linked to a significantly higher risk for all-cause mortality in patients with NSCLC, implying that effectively controlling diabetes or hyperglycemia could improve prognosis in patients with NSCLC and abnormal glucose levels.³

References

1. Llop Serna S, Puig E, Palmero R, et al. Impact of high fasting plasma glucose in the clinical outcome of patients with advanced NSCLC with PD-L1 ≥ 50% treated with frontline pembrolizumab. Ann Oncol. 2021;32(suppl 5):S1012.
2. Li W, Zhang X, Sang H, et al. Effects of hyperglycemia on the progression of tumor diseases. J Exp Clin Cancer Res. 2019;38:327.
3. Luo J, Chen Y-J, Chang L-J. Fasting blood glucose level and prognosis in non-small cell lung cancer (NSCLC) patients. Lung Cancer. 2012;76:242-247.