Nimotuzumab combined with gemcitabine versus gemcitabine in K-RAS wild-type locally advanced or metastatic pancreatic cancer: A prospective, randomized-controlled, double-blinded, multicenter, and phase III clinical trial.

LBA4011 Background: Pancreatic cancer is one of the most lethal malignancies diagnosed at an advanced stage, and current treatment regimens are ineffective, with only 6-8 months of median overall survival (mOS). The present study aims to assess the clinical efficacy and safety of nimotuzumab (anti-EGFR humanized monoclonal antibody) combined with gemcitabine in K-Ras wild-type patients with locally advanced or metastatic pancreatic cancer. Methods: Patients with locally advanced or metastatic pancreatic cancer were randomized to receive nimotuzumab (400 mg, every one week) followed by gemcitabine (1000 mg/m 2 on days 1, 8, and 15, every four weeks), or placebo plus gemcitabine until progression or unacceptable toxicity. The primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. Use restricted mean survival time (RMST)-Log function to analyze the survival benefits when the proportional hazards assumption is untrue. Results: A total of 92 Chinese patients were randomly assigned to the nimotuzumab- gemcitabine (n = 46) or placebo-gemcitabine group (n = 46). In the full analysis set (FAS, n = 82), the mOS was significantly longer in the nimotuzumab-gemcitabine group (10.9 vs. 8.5 months, p = 0.025 by RMST-Log test, hazard ratio [HR], 0.50, 95% Confidence Interval [CI], 0.06 to 0.94). The one-year survival rate was 43.6% in the nimotuzumab-gemicitabine group vs. 26.8% in the placebo-gemicitabine group, and 13.9% vs. 2.7% at three years. Subgroup analyses showed more survival benefit in patients without treatment of biliary obstruction (11.9 vs. 8.5 months, HR = 0.54, 95%CI 0.33-0.88, p = 0.037) and no surgical history (15.8 vs. 6.0 months, HR = 0.40, 95%CI 0.19-0.84). The median progression-free survival (mPFS) was 4.2 months in the nimotuzumab-gemicitabine group, as compared with 3.6 months in the placebo-gemicitabine group (HR = 0.56; 95% CI, 0.12 to 0.99; p = 0.013 ); Patients without treatment of biliary obstruction had significantly longer PFS (5.5 vs. 3.4 months; p = 0.008 ). No statistical difference in the ORR between the two groups ( p > 0.05). Nimotuzumab was safe and the incidence of adverse events in the nimotuzumab-gemicitabine group is similar to placbo-gemicitabine group. The most common grade 3 TRAEs in Nim-Gem group were neutropenia (11.1%), leukopenia (8.9%) and thrombocytopenia (6.7%). No grade 4 TRAEs. Conclusions: Nimotuzumab combined with gemcitabine increases OS and PFS in patients with K-Ras wild-type locally advanced or metastatic pancreatic cancer, particularly for those without treatment of biliary obstruction. The safety profile of nimotuzumab is similar to placebo. Clinical trial information: 02395016.