Efficacy and Safety of Single-Agent Pertuzumab, a Human Epidermal Receptor Dimerization Inhibitor, in Patients with Non–Small Cell Lung Cancer

摘要: Purpose: Pertuzumab, a first-in-class human epidermal receptor 2 (HER2) dimerization inhibitor, is humanized monoclonal anti-HER2 antibody that binds HER29s domain and inhibits HER2 signaling. Based on supporting preclinical studies, we undertook Phase II trial of pertuzumab in patients with recurrent non–small cell lung cancer (NSCLC). Experimental Design: Patients previously treated NSCLC accessible for core biopsy naive to HER pathway inhibitors were i.v. once every 3 weeks. Tumor assessments done at 6 12 weeks then months thereafter. The primary efficacy end point was overall response rate by Response Evaluation Criteria Solid Tumors. Measurement tumor glucose metabolism (SUV max ) F-18-fluorodeoxyglucose positron emission tomography used as an exploratory pharmacodynamic marker drug activity. Results: Of 43 pertuzumab, no responses seen; 18 (41.9%) 9 (20.9%) had stable disease weeks, respectively. median 3-month progression-free survival rates (PFS) 6.1 (95% confidence interval, 5.3-11.3 weeks) 28.4% 14.4-44.2%), 22 who underwent tomography, six (27.3%) metabolic evidenced decreased SUV . These prolonged PFS (HR = 0.11, log-rank P value 0.018) compared the 16 response. Four (9.3%) experienced grade 3/grade 4 adverse event judged related pertuzumab; none exhibited cardiac toxicity. Conclusions: Pertuzumab well tolerated monotherapy. Pharmacodynamic activity correlated detected moderate percentage (27.3%). Further clinical development should focus rational combinations other drugs active NSCLC.