Despite the overall survival (OS) benefit, only 18-20% of aNSCLC patients respond to immune-checkpoint inhibitors (ICI) as second-line therapy with a median progression-free survival (mPFS) of 2-4 months. The identification of predictive and prognostic biomarkers to select patients most likely to respond to ICI is greatly needed in guiding clinical practice.
We conducted a retrospective monocentric analysis of 154 aNSCLC patients receiving single-agent Nivolumab or Pembrolizumab as second-line (68%) and >3rd line (32%). We collected complete blood cell count at baseline and evaluated LDH, absolute neutrophil count (ANC), lymphocyte count (ALC), monocyte count (AMC) and eosinophil count (AEC) and their ratio such as neutrophil-lymphocyte ratio (NLR), derived-NLR (dNLR) and lymphocyte-monocyte ratio (LMR). Univariate and multivariate analyses were performed to identified indipendent predictors factors for immunotherapy (using Kaplan–Meier and Cox Progression analyses).
The multivariate analysis on clinical factors showed the negative predictive role of ECOG PS 2 and liver metastasisand the positive predicitive role of smoking status. The multivariate analysis for PFS showed the negative predictive role of higher ANC (>6000/mL) and LDH (>400 mg/dl) and positive predictive role of higher ALC (>2200/mL). Also, according to stepwise regression analyses, NLR>4 playsa negative predictive and prognostic role at baseline. Finally, five predictive clinical and blood biomarkers at baseline (smoking status, ECOG PS, liver metastases, LDH and NLR), were used to create a predictive score for immunotherapy. Three predictive groups were defined as high, intermediate and low with a mPFS of 10.2 vs 4.9 vs 1.7 months respectively (HR 4.18 95% IC 2.64–6.62, p < 0.001).Table: 6P
|ECOG PS||0-1 2||0 1|
|Smoking (pack-years)||> 43 < 43||0 1|
|Liver metastases||No Yes||0 1|
|LDH (mg/dl)||< 400 > 400||0 1|
|NLR||< 4 > 4||0 1|
|Predictive groups (Points): 1 = 0 2 = 1-2 3 = 3-5||PFS (months): 10.2 4.9 1.7||HR 4.18 95% IC (2.64 – 6.62) p < 0.001|
In advanced NSCLC patients treated with second-line immunotherapy, the identification of five and predictive clinical and blood biomarkers at baseline, combined in a predictive score, may help identify patients most likely to benefit from immunotherapy.
Clinical trial identification
Legal entity responsible for the study
Clinical Cancer Center Giovanni Paolo II, Bari, Italy.
Has not received any funding.
G. Domenico: Advisory board: Bristol-Myers Squibb. All other authors have declared no conflicts of interest.