Pretreatment advanced lung cancer inflammation index (ALI) for predicting early progression in nivolumab‐treated patients with advanced non–small cell lung cancer

Abstract

Programmed death‐ligand 1 (PD‐L1) expression status is inadequate for indicating nivolumab in patients with non–small cell lung cancer (NSCLC). Because the baseline advanced lung cancer inflammation index (ALI) is reportedly associated with patient outcomes, we investigated whether the pretreatment ALI is prognostic in NSCLC patients treated with nivolumab. We retrospectively reviewed the medical records of all patients treated with nivolumab for advanced NSCLC between December 2015 and May 2016 at three Japanese institutes. Multivariate logistic regression and Cox proportional hazards models were used to assess the impact of the pretreatment ALI (and other inflammation‐related parameters) on progression‐free survival (PFS) and early progression (i.e., within 8 weeks after starting nivolumab). A total of 201 patients were analyzed; their median age was 68 years (range, 27–87 years), 67% were men, and 24% had an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or higher. An ECOG performance status ≥2, serum albumin <3.7 g/dL, neutrophil‐to‐lymphocyte ratio ≥4, and ALI <18 were significantly associated with poor PFS and early progression on univariate analysis. Multivariate analyses revealed that pretreatment ALI <18 was independently associated with inferior PFS (median, 1.4 vs. 3.7 months, P < 0.001) and a higher likelihood of early progression (odds ratio, 2.76; 95% confidence interval 1.44–5.34; P = 0.002). The pretreatment ALI was found to be a significant independent predictor of early progression in patients with advanced NSCLC receiving nivolumab, and may help identify patients likely to benefit from continued nivolumab treatment in routine clinical practice.

A reliable and feasible way to predict the benefits of Nivolumab in patients with non-small cell lung cancer: a pooled analysis of 14 retrospective studies

“…After removing duplication and reviewing titles and abstracts, 126 of them were discarded and the left 18 studies were included for more detailed selection. Finally, 130 of the initial studies were excluded and the left 14 retrospective studies 16–19,26–35 were considered as eligible for the combined analysis after reviewing the full text. We also planned to assess the role of NLR in predicting anti-PD-1/PD-L1 agents, including Pembrolizumab, Atezolizumab, and Durvalumab.…”

“…We extracted data of PFS and OS from individual studies 16–19,26–35 . As shown in Supplemental Table 1, the median OS ranged from 6.5 to 17 months, while the median PFS was between 2.1 and 5.5 months.…”

“…By combining HRs of high NLR versus low NLR with regard to PFS from 10 studies, 16–19,26,28,32,33,35,36 the pooled result using random effect model showed that the estimated effect was 1.44(95%CI: 1.18, 1.77), indicating NSCLC patients with low pre-treatment NLR had a 1.44 times of getting better PFS(Figure 2A). As shown in Figure 2B, the pooled HRs of OS from eight studies 16,18,19,28,30,33,35,36 using random effect model was 1.75(95%CI: 1.33, 2.30), favoring NSCLC patients with low pre-treatment NLR.

10.1080/2162402X.2018.1507262-F0002Figure 2.Comparisons of PFS and OS in Nivolumab treated NSCLC patients with different baseline NLR.

…”

“…Seven studies 17–19,26,29,30,33 reported number of patients achieved ORR and DCR after treatment of Nivolumab (Supplemental Table 3). In a total of 716 patients, 141 were considered as ORR and 236 as DCR, with percentages of 19.69% and 32.96%, respectively.…”

“…The studies 16-19,26,28,32,33,35,36 included reported the HRs of high NLR versus low NLR on PFS in the treatment of advanced NSCLC. As shown in Figure 3A, the estimated effect of NLR < 5 was 1.19 (95%CI: 1.00, 1.41; p = 0.06), and it was 1.73(95%CI: 1.14, 2.62; p = 0.009) for NLR ≥ 5.…”