The Role of Relative Lymphocyte Count as a Biomarker for the Effect of Catumaxomab on Survival in Malignant Ascites Patients: Results from a Phase II/III Study

TY - JOUR

T1 - The Role of Relative Lymphocyte Count as a Biomarker for the Effect of Catumaxomab on Survival in Malignant Ascites Patients: Results from a Phase II/III Study

AU - Heiss, Markus M

AU - Ströhlein, Michael A

AU - Bokemeyer, Carsten

AU - Arnold, Dirk

AU - Parsons, Simon L

AU - Seimetz, Diane

AU - Lindhofer, Horst

AU - Schulze, Elisabeth

AU - Hennig, Michael

N1 - ©2014 American Association for Cancer Research.

PY - 2014/6/15

Y1 - 2014/6/15

N2 - PURPOSE: We report the role of relative lymphocyte count (RLC) as a potential biomarker with prognostic impact for catumaxomab efficacy and overall survival (OS) based on a post hoc analysis of the pivotal phase II/III study of intraperitoneal catumaxomab treatment of malignant ascites.EXPERIMENTAL DESIGN: The impact of treatment and RLC on OS was evaluated using multivariate Cox models. Kaplan-Meier and log-rank tests were used for group comparisons. Survival analyses were performed on the safety population [patients with paracentesis plus ≥1 dose of catumaxomab (n = 157) and paracentesis alone (n = 88)]. Determination of the optimal cutoff value for RLC was based on five optimality criteria.RESULTS: OS was significantly longer with catumaxomab versus paracentesis alone (P = 0.0219). The 6-month OS rate with catumaxomab was 28.9% versus 6.7% with paracentesis alone. RLC had a positive impact on OS and was an independent prognostic factor (P < 0.0001). In patients with RLC > 13% (n = 159: catumaxomab, 100 and control, 59), catumaxomab was associated with a favorable effect on OS versus paracentesis alone (P = 0.0072), with a median/mean OS benefit of 41/131 days and an increased 6-month survival rate of 37.0% versus 5.2%, respectively. In patients with RLC ≤ 13% at screening (n = 74: catumaxomab, 50 and control, 24), the median (mean) OS difference between the catumaxomab and the control group was 3 (16) days, respectively (P = 0.2561).CONCLUSIONS: OS was significantly improved after catumaxomab treatment in patients with malignant ascites. An RLC > 13% at baseline was a significant prognostic biomarker. Clin Cancer Res; 20(12); 3348-57. ©2014 AACR.

AB - PURPOSE: We report the role of relative lymphocyte count (RLC) as a potential biomarker with prognostic impact for catumaxomab efficacy and overall survival (OS) based on a post hoc analysis of the pivotal phase II/III study of intraperitoneal catumaxomab treatment of malignant ascites.EXPERIMENTAL DESIGN: The impact of treatment and RLC on OS was evaluated using multivariate Cox models. Kaplan-Meier and log-rank tests were used for group comparisons. Survival analyses were performed on the safety population [patients with paracentesis plus ≥1 dose of catumaxomab (n = 157) and paracentesis alone (n = 88)]. Determination of the optimal cutoff value for RLC was based on five optimality criteria.RESULTS: OS was significantly longer with catumaxomab versus paracentesis alone (P = 0.0219). The 6-month OS rate with catumaxomab was 28.9% versus 6.7% with paracentesis alone. RLC had a positive impact on OS and was an independent prognostic factor (P < 0.0001). In patients with RLC > 13% (n = 159: catumaxomab, 100 and control, 59), catumaxomab was associated with a favorable effect on OS versus paracentesis alone (P = 0.0072), with a median/mean OS benefit of 41/131 days and an increased 6-month survival rate of 37.0% versus 5.2%, respectively. In patients with RLC ≤ 13% at screening (n = 74: catumaxomab, 50 and control, 24), the median (mean) OS difference between the catumaxomab and the control group was 3 (16) days, respectively (P = 0.2561).CONCLUSIONS: OS was significantly improved after catumaxomab treatment in patients with malignant ascites. An RLC > 13% at baseline was a significant prognostic biomarker. Clin Cancer Res; 20(12); 3348-57. ©2014 AACR.

U2 - 10.1158/1078-0432.CCR-13-2351

DO - 10.1158/1078-0432.CCR-13-2351

M3 - SCORING: Journal article

C2 - 24714773

VL - 20

SP - 3348

EP - 3357

JO - CLIN CANCER RES

JF - CLIN CANCER RES

SN - 1078-0432

IS - 12

ER -