The Prognostic Value of Pre-Treatment Leukocytosis in Patients with Previously Treated, Stage IIIB/IV Non-Small Cell Lung Cancer Treated with the IGF-1R Pathway Modulator AXL1717 or Docetaxel; a Retrospective Analysis of a Phase II Trial

Abstract

<br /> <strong><span style="font-size: small;">Background: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">The aim of the present study was to investigate any prognostic value of pre-treatment anemia, leukocytosis and thrombocytosis in patients with advanced pretreated NSCLC. </span></span><strong><span style="font-size: small;">Methods: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">A randomized, multicenter phase II study comparing the IGF-1R modulator AXL with standard docetaxel in the treatment of previously treated stage IIIB or IV NSCLC patients was conducted in 2011-2013. Clinical and laboratory data were collected, including serum values for hemoglobin (Hgb), white blood cells (WBC) and platelets (Plt) at baseline. These hematological parameters were studied in relation to overall survival using Kaplan–Meier product-limit estimates and multivariate Cox proportional hazards regression models. </span></span><strong><span style="font-size: small;">Results: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">The median overall survival for all patients was 8.9 months. Patients with leukocytosis (WBC > 9 x 10</span></span><span style="font-family: Times New Roman,Times New Roman; font-size: xx-small;"><span style="font-family: Times New Roman,Times New Roman; font-size: xx-small;">9</span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">/L) had a significantly shorter median overall survival (4.2 months) as compared with those with a WBC ≤ 9 x 10</span></span><span style="font-family: Times New Roman,Times New Roman; font-size: xx-small;"><span style="font-family: Times New Roman,Times New Roman; font-size: xx-small;">9</span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">/L at baseline (12.3 months) with a corresponding of HR 2.10 (95% CI: 1.29-3.43). </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">Patients with anemia (Hgb < 110 g/L) had a non-significant (p = 0.097) shorter median overall survival (6.1 months) as compared with their counterparts with Hgb ≥ 110 g/L at baseline (9.4 months). As for thrombocytosis (Plt > 350 x 10</span></span><span style="font-family: Times New Roman,Times New Roman; font-size: xx-small;"><span style="font-family: Times New Roman,Times New Roman; font-size: xx-small;">9</span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">/L), </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">there was no statistically significant impact on overall survival. Leukocytosis retained its prognostic significance </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">in a multivariate model where other clinical factors such as age, sex and WHO performance status were taken into </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">consideration (HR: 1.83, 95% CI: 1.06-3.13, p = 0.029). </span></span><strong><span style="font-size: small;">Conclusion: </span></strong><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">Pre-treatment leukocytosis is a strong and independent prognostic marker for shorter overall survival in previously treated stage IIIB or IV NSCLC patients </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">receiving docetaxel or AXL1717. Combined use of pre-treatment leukocytosis assessments together with established </span></span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">prognostic factors such as performance status could be of help when making treatment decisions in this clinical setting. </span></span>