Inflammation-Based Biomarker Has a Prognostic Role in ALK+ NSCLC

Pan-immune-inflammation value (PIV), which is an inflammation-based biomarker that measures neutrophils, platelets, monocytes, and lymphocyte counts, may have a prognostic role in determining progression-free survival (PFS) and overall survival (OS) in patients with ALK-positive non–small cell lung cancer (NSCLC), according to a study published in Translational Oncology.¹

Investigators determined that the 1-year PFS was 63.5% and the 5-year OS rate was 55.1%. They noted that patients with a higher PIV, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) had a worse PFS, according to univariate analysis. Only the PIV was determined to be an independent prognostic factor, according to multivariate analysis (HR, 2.90; 95% CI, 1.79-4.70; P < .001).

Patients at the Sun Yat-Sen University Cancer Center in Guangzhou, China, with ALK-positive NSCLC, who were initially treated with ALK tyrosine kinase inhibitors (TKIs; n = 264), were evaluated. To be eligible for the trial, patients had to have histologically or cytologically confirmed unresectable, locally advanced, or metastatic NSCLC, an ALK rearrangement that was detected by fluorescence in situ hybridization or Ventana immunohistochemistry, received oral ALK TKIs in the first line, and pretreatment absolute counts of peripheral blood neutrophils, monocytes, platelets, and lymphocytes. Baseline characteristics such as age, gender, smoking history, histology, cancer stage, and number of metastatic sites were collected. Statistical analysis of PFS was calculated from the date of initial treatment to the date of disease progression or patient death from any cause. PFS and OS were esti- mated using Kaplan-Meier, and comparisons were carried out using the log-rank test.

Ninety-four patients were determined to be evaluable. A breakdown of first-line treatment showed most patients received crizotinib (89.4%; Xalkori), alectinib (10.6%; Alecensa), or ceritinib (1.0%; Zykadia). The median base- line PIV was 364 (range, 55.2-6840.4). The median baseline readings for NLR, PLR, and SII were 3 (range, 0.8-10.8), 158 (range, 22.8- 652.5), and 842 (158.0-4997.0), respectively.

Patients with high PIV had more than 1 site of metastasis compared with low PIV (P =.038). No significant differences between low and high PIV were observed when stratified by sex, smoking status, histology, cancer stage, or first-line ALK TKI regimen.

The prognostic value of different systemic inflammation markers has been reported in patients with NSCLC, especially in the EGFR-mutated population. However, few studies have analyzed the prognostic value of the peripheral inflammatory blood markers in patients with ALK-positive NSCLC receiving ALK TKIs as first-line treatment.

Effect of Parameters on PFS

Median follow-up time for PFS was 47.0 months (interquartile range, 38.5-55.5), and a total of 73 tumor progression events were observed. One-year and 3-year PFS rates were 63.5% and 24.1%, respectively. PFS favored low PIV at 25.7 months (95% CI, 16.4-34.9) compared with 10.3 months for high PIV (95% CI, 8.0-12.6; P <.001).

Patients with lower PLR had a median PFS of 21.3 months (95% CI, 14.4-28.1) vs those with a high PLR, who had a median PFS of 13.0 months (95% CI, 10.1-15.9; P =.004). In patients with low SII, the median PFS was 25.7 months (95% CI, 18.6-32.7) vs 10.9 months for high SII (95% CI, 8.0-13.9; P < .001).

When all variables were analyzed using multivariate analysis, only a higher PIV (HR, 2.9; 95% Cl, 1.79-4.70; P <.001), liver metastases (HR, 3.60; 95% Cl, 2.01-6.44; P<.001), and brain metastases (HR, 1.68; 95% Cl, 1.01-2.78; P = .045) were determined to be independent prognostic factors for poor median PFS.

Effect of Parameters on OS

Investigators reported 32 deaths during the follow-up period, and the median OS was not reached. Three-year and 5-year OS rates were 70.4% and 55.1%, respectively. Median OS was not reached for patients with low PIV compared with 38.7 months (95% CI, 28.2-49.2; P < .001) for high PIV. In addition, lower NLR, PLR, and SII were also associated with longer median OS (P = .006; P = .008; and P = .001, respectively).

Poor median OS was associated with number of metastatic sites, liver metastasis, PIV, NLR, PLR, and SII, according to univariate analysis. Higher PIV (HR, 4.70; 95% CI, 2.00-11.02; P <.001) and liver metastasis (HR, 5.16; 95% CI, 2.42-11.01; P <.001) were independently associated with survival outcomes, according to multivariate analysis.

Giovanni Fucà et al, first demonstrated that PIV was a strong predictor of survival outcomes with better performance in patients with colorectal cancer who were treated with first-line therapy.² Another study found that high PIV did not show a statistically significant and independent association with worse PFS but was independently associated with worse OS in patients with HER2-positive advanced breast cancer patients who received first-line trastuzumab (Herceptin) and pertuzumab (Perjeta).³

The investigators noted several limitations with their study, including its retrospective nature with accompanying biases, its monocentric design and small sample size, and the lack of a validation group to confirm results. Notably, approximately 90% of patients were treated with crizotinib as first-line therapy in the study and only 10 patients received second-generation TKIs, including alectinib or ceritinib, which have been successfully and routinely used as first-line therapy for patients with advanced ALK-positive NSCLC.

_REFERENCES

_{1. Chen X, Hong X, Chen G, et al. The Pan-Immune-Inflammation Value predicts the survival of patients with anaplastic lymphoma kinase-pos- itive non-small cell lung cancer treated with first-line ALK inhibitor. Transl Oncol. 2022;17:101338. doi:10.1016/j.tranon.2021.101338}

_{2. Fucà G, Guarini V, Antoniotti C, et al. The Pan-Immune-Inflammation Value is a new prognostic biomarker in metastatic colorectal cancer: re- sults from a pooled-analysis of the Valentino and TRIBE first-line trials. Br J Cancer. 2020;123(3):403-409. doi:10.1038/s41416-020-0894-7 3}

_{. Ligorio F, Fucà G, Zattarin E, et al. The Pan-Immune-Inflamma- tion-Value predicts the survival of patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer treated with first-line taxane-trastuzumab-pertuzumab. Cancers (Basel). 2021;13(8):1964. doi:10.3390/cancers13081964}