Pretreatment Prognostic Score May Determine Immunotherapy Response in Advanced NSCLC

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One of the leading causes of cancer-related deaths worldwide is lung cancer. Non–small-cell lung cancer (NSCLC) makes up approximately 85% of lung cancer cases. Most patients are diagnosed at an advanced stage, and the 5-year survival rate is poor—5%. Recently, with the introduction of immune checkpoint inhibitors (ICIs), long-term survival rates have improved for patients with advanced NSCLC. Although many patients respond well to ICIs, a small percentage of patients do not respond well or at all. PD-L1 expression is a common immunomarker that has been correlated with immunotherapy efficacy and is listed as such in the National Comprehensive Cancer Network guidelines. However, the CheckMate-026 study found that in patients with high PD-L1 expression, ICI use conveyed no significant progression-free survival (PFS) or overall survival (OS) benefits.

Researchers are seeking other biomarkers that can determine which patients with advanced NSCLC may benefit from the use of ICIs. Inflammatory biomarkers such as lactate dehydrogenase (LDH), albumin, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index, and systemic inflammation response index are readily available in clinical practice and were studied in a retrospective analysis to determine if these biomarkers were associated with treatment response and if they could be used to guide treatment in patients with advanced NSCLC, and to explore the association between these biomarkers and survival.

A total of 101 patients with advanced NSCLC were evaluated in this study. The patients had been treated with PD-1/PD-L1 inhibitors and had received ≥1 cycles of ICI. Most patients (77.2%) were male, 72.3% had a history of smoking, and 22.8% had a PD-L1 expression ≥50%. Objective response rate (ORR), disease control rate (DCR), OS, and PFS were evaluated.

Independent predictors of ORR were high LDH, any grade immune-related adverse events (irAEs), and NSCLC clinical stage. DCR independent predictors were LDH and ICI treatment types. For OS, there were more independent factors identified: LDH, albumin, Eastern Cooperative Oncology Group performance status (ECOG PS), PLR, NLR, and any grade irAEs. For PFS, independent factors were patient clinical stage, albumin, LDH, and any grade irAEs.

The study also explored whether a pretreatment prognostic score could be determined. Scores were established based on the following factors: ECOG PS, LDH, albumin, PLR, and the patient’s clinical stage. Researchers established 3 groups based on these factors: good group (0-1 score), intermediate group (2 scores), or poor group (≥3 scores). A poor score had a strong negative association with survival in patients with PD-L1 expression ≥50%. The study also found that in this patient group, high serum albumin (an indicator of nutritional status) before immunotherapy increased survival chance.

The researchers concluded that “Pre-treatment prognostic score based on clinical stage, ECOG PS, LDH, albumin, and PLR may help to identify advanced NSCLC patients who may benefit from ICIs.”


  • Wu Y, Wu H, Lin M, Liu T, Li J. Factors associated with immunotherapy respond and survival in advanced non-small cell lung cancer patients. Transl Oncol. 2022;15(1):101268.

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