Anti-EML4 monoclonal antibody, clone 3G3

Background: Targeted therapy is an important treatment for advanced non-small cell lung cancer (NSCLC) patients with specific genetic mutations, crizotinib can prolong survival in advanced NSCLC patients with echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) rearrangement. We performed a retrospective analysis to investigate the association between the lactate dehydrogenase (LDH) levels and progression-free survival (PFS) in patients with EML4-ALK rearrangement NSCLC receiving treatment with crizotinib. Methods: Advanced (stage IIIb-IV) NSCLC patients with EML4-ALK rearrangement receiving treatment with crizotinib were enrolled between January 2007 and January 2016 at Peking Union Medical College and Cancer Hospital Chinese Academy of Medical Sciences. Results: Overall, 212 patients were enrolled. Kaplan-Meier univariate analysis showed that elevated pre-treatment LDH level (7.9 vs 14.1 months, HR =1.251, CI: 1.008-1.553, P=0.004) was significantly associated with shorter PFS, while the post-treatment mean-LDH level (13.3 vs 14.3 months, HR=1.439, 95% CI: 0.994-2.082, P=0.970) was not significantly associated with PFS. Cox proportional hazards model also identified that pretreatment LDH level (HR=2.085, 95% CI: 1.150-3.781, P=0.016) was associated with the PFS. Logistic regression analysis showed that post-treatment LDH level was associated with creatine kinase (OR=6.712, 95% CI 3.395-13.273, P<0.01), creatine kinase isoenzyme (OR=6.297, 95% CI 2.953-13.427, P<0.01), and hemoglobin (OR=4.163, 1.741-9.956, P<0.001). Conclusion: An elevated pre-treatment serum LDH level (>250 U/L) was significantly associated with shorter PFS in patients with EML4-ALK rearrangement NSCLC. Post-treatment elevated serum LDH level was not significantly associated with PFS, which related to adverse events including muscle damage and anemia.

Background: The aim of this study was to analyse the epidemiological characteristics and clinical features of the three driver genes EGFR, ALK and ROS1 in Chinese patients with non-small-cell lung cancer (NSCLC). Methods: EGFR mutations, ALK fusions and ROS1 rearrangements were detected simultaneously by quantitative real-time PCR. Subgroup analyses were performed for adenocarcinoma and squamous cancer. The Chi-square test and multivariate logistic regressive analysis were used to analyse the associations between gene alterations and clinical features. Result: A total of 3,081 patients with pathologically confirmed NSCLC from five sites in China were enrolled, among whom 1,449 (47.03%) had EGFR, ALK and/or ROS1 alterations. In adenocarcinoma, the alteration rates of EGFR, ALK and ROS1 were 50.6% (1,193/2,360), 6.3% (148/2,360), and 1.6% (38/2,360), respectively. EGFR and EML4-ALK coexisted in 16 cases (0.5%), while EGFR and ROS1 coexisted in I case (0.03%). Sex, smoking status, and tumour stage were significantly correlated with the EGFR mutation; age and smoking status were correlated with EML4-ALK; and age and tumour stage were correlated with ROS1. In squamous cancer, the alteration rates of EGFR, ALK and ROS1 were 7% (34/488), 2.9% (14/488) and 0% (0/488), respectively. Sex and smoking history were associated with EGFR, and sex was the only independent predictor of EGFR. The EGFR gene mutation sites were mainly 19del (557/1,263; 44.1%) and 21 exon L858R (575/1,263; 45.5%). More uncommon EGFR mutation types were present in 10.4% (131/1,263) of patients. Patients with EGFR, ALK, and/or ROS1 alterations had different epidemiological characteristics and clinical features. Conclusions: This real-word study of alterations in driver genes in a large population in China revealed unique epidemiological characteristics and clinical features in Chinese patients with NSCLC.