Standard treatments for patients with lung cancer include surgery, radiation therapy, chemotherapy, targeted therapy, and immunotherapy.1 Treatment depends on a number of factors, including cancer stage, treatment side effects, patient preferences, and the overall health of the patient.1 Immunotherapy with the immune checkpoint inhibitors (ICIs) that block the PD-1/PD-L1 or CTLA-4 pathways are often chosen as first-line therapy for patients with non–small-cell lung cancer (NSCLC), but in patients with poor performance status (PS) ICI use may not improve the patient’s health. Treatment with PD-1 blockade in patients with NSCLC with a poor PS is controversial, as studies have demonstrated that PS is an important prognostic factor for predicting poor response to ICI treatment in patients with NSCLC.
A review of the clinical effectiveness of ICI use in patients with NSCLC and poor PS was published in Medicina to address these issues. Several studies demonstrated that in patients with advanced or recurrent NSCLC treated with PD-1 monotherapy, PS was an independent factor for the prediction of worse outcomes. There were statistical differences in progression-free survival and objective response rate. The standard of care for patients with NSCLC with PD-L1 ≥50% is pembrolizumab. In patients with NSCLC and a PS of 2, the use of pembrolizumab or atezolizumab as first-line therapy appears to be effective if PD-L1 expression is >50%. However, meta-analysis and literature reviews indicate that the objective response rate and disease control rate are significantly reduced in patients with a PS of 2 to 4 when compared with patients with a PS of 0 or 1.
When comorbidity burden is the cause of poor PS, these patients can derive benefits using pembrolizumab as first-line therapy, as it is thought that the comorbidities do not reduce immune response. A higher body mass index has been reported in several studies to be related to favorable survival in patients with NSCLC, renal-cell carcinoma, and melanoma who were treated with ICI, indicating that body mass index may have an association with the efficacy of ICI. Obesity may possibly increase the number of tumor-infiltrating lymphocytes that are responsive to PD-1 blockade. Patients with a poor PS may have a tumor microenvironment that is resistant to PD-1 blockade. Other factors that may contribute to a poor response to PD-1 blockade include the presence of high levels of serum vascular endothelial growth factor, a high pretreatment level of neutrophil-to-lymphocyte ratio, and concomitant use of steroids or antibiotics.
Source
Kaira K, Imai H, Mouri A, et al. Clinical effectiveness of immune checkpoint inhibitors in non-small-cell lung cancer with a poor performance status. Medicina (Kaunas). 2021;57:1273.
Reference
- Cancer.net. Lung cancer non-small cell: types of treatment. Updated November 2021. www.cancer.net/cancer-types/lung-cancer-non-small-cell/types-treatment. Accessed February 22, 2022.
