Metastatic non–small-cell lung cancer (NSCLC) is a recognized risk factor for venous thromboembolism (VTE). Some systemic treatments may increase this risk further. Young and colleagues presented data on the risk of VTE and its prognostic significance in patients treated with chemotherapy (chemo) and the EGFR monoclonal antibody necitumumab (neci) for metastatic NSCLC.1 Four trials of first-line treatment for Stage IV NSCLC were included in this analysis, including SQUIRE (N = 1079) and INSPIRE (N = 616), which were randomized phase 3 studies of cisplatin/gemcitabine ± neci in squamous NSCLC and cisplatin/pemetrexed ± neci in nonsquamous NSCLC, respectively; JFCL (N = 161), which was a randomized phase 2 study of carboplatin/paclitaxel ± neci in squamous NSCLC; and JFCK (N = 61), which was a single-arm study of cisplatin/gemcitabine + neci in squamous NSCLC. VTE risk was explored in each study in a univariate analyses. On-treatment VTE across studies ranged from 3.6% to 8.3% for chemo alone and 3.8% to 13.2% for neci + chemo. Neci + chemo was associated with an increased VTE risk in SQUIRE (relative risk [RR], 1.699; confidence interval [CI], 1.09-2.65), INSPIRE (RR, 1.58; CI, 0.99-2.52), and JFCL (RR, 1.04; CI, 0.20-5.49) compared with chemotherapy alone. A previous history of VTE was the strongest predictor of VTE in SQUIRE (RR, 2.63; CI, 1.296-5.34) and INSPIRE (RR, 1.62; CI, 0.79-3.33). In SQUIRE, other baseline risk factors with RR >1.00 included age >65 years, hemoglobin <10 g/dL, body mass index >35 kg/m2, and current smoking. Occurrence of VTE at any time was not associated with shorter overall survival in randomized trials: hazard ratio (HR), 1.06; CI, 0.85-1.33 (SQUIRE); HR, 0.99; CI, 0.76-1.27 (INSPIRE); HR, 1.16; CI, 0.56-2.41 (JFCL). The authors concluded that although VTE was more frequent in patients on neci + chemo versus chemo alone, it was not associated with shorter overall survival, and that a history of VTE was the most significant risk factor for VTE occurrence.
