Nimotuzumab May Effectively Target KRAS Wild-Type Pancreatic Cancer

The epidermal growth factor receptor (EGFR)–targeted tyrosine kinase inhibitor gefitinib is FDA-approved to combine with gemcitabine in metastatic pancreatic cancer. However, the benefits are marginal, and more-effective systemic therapies have replaced this treatment option. Mutations in KRAS, which are present in nearly 90% of pancreatic cancers, may mitigate any benefit for EGFR-targeted agents.

Investigators report results of an industry-sponsored, randomized, placebo-controlled trial in patients with KRAS wild-type advanced pancreatic cancer who had received no prior chemotherapy for metastatic disease. Patients received weekly gemcitabine for 3 weeks on and 1 week off combined with either placebo or the EGFR-targeting monoclonal antibody nimotuzumab given weekly. Of 480 patients screened for KRAS wild-type status, 82 (17%) were identified; median age was 55, 56% had undergone prior surgery, and 7% had received prior adjuvant chemotherapy.

The primary endpoint of overall survival (OS) trended higher with nimotuzumab compared with placebo (median, 10.9 vs. 8.5 months; hazard ratio, 0.66; P=0.08). Progression-free survival was longer with nimotuzumab compared with placebo (median, 4.2 vs. 3.6 months; HR, 0.60; P=0.04). Rates of response (7.3% and. 9.8%) and disease control (63.4% and 68.3%) were similar between treatment arms. Rates of adverse events were also similar between the two arms.