Battaglin Francesca, Dadduzio Vincenzo, Bergamo Francesca, Manai Chiara, Schirripa Marta, Lonardi Sara, Zagonel Vittorina, Loupakis Fotios
a Clinical and Experimental Oncology Department, Medical Oncology Unit 1 , Veneto Institute of Oncology IOV - IRCCS , Padova , Italy.
Expert Opin Biol Ther. 2017 Oct;17(10):1297-1308. doi: 10.1080/14712598.2017.1356815. Epub 2017 Jul 28.
Targeted agents alone or in combination with chemotherapy are current standard of treatment for metastatic colorectal cancer (mCRC). Panitumumab is a fully human monoclonal antibody which inhibits the epidermal growth factor receptor (EGFR). It is currently approved in combination with chemotherapy in first- and second-line and as a monotherapy in chemorefractory patients. RAS gene mutations confer resistance to anti-EGFR agents; thus, panitumumab is restricted to the treatment of RAS wild-type (WT) tumors. Areas covered: This review explores the available data on panitumumab and presents new perspectives on predictive markers of anti-EGFR efficacy including primary tumor sidedness and BRAF mutations. Other details covered include panitumumab's mechanism of action, pharmacokinetics, pharmacodynamics and safety aspects of the therapy as well as mechanisms of secondary resistance and future prospects of treatment in different settings. Expert opinion: Panitumumab has significantly added to the treatment armamentarium for RAS WT mCRC. The effort spent in identifying predictive biomarkers of panitumumab efficacy has been of pivotal importance to development of the molecular selection of patients with mCRC. Primary and secondary resistance, however, still represent important issues. Novel strategies to overcome those issues are currently underway with promising results which highlight the potential use of panitumumab in combination with other targeted agents in the future.
靶向药物单药治疗或与化疗联合使用是目前转移性结直肠癌(mCRC)的标准治疗方案。帕尼单抗是一种完全人源化单克隆抗体,可抑制表皮生长因子受体(EGFR)。目前,它被批准与化疗联合用于一线和二线治疗,并作为单药用于化疗难治性患者。RAS基因突变会导致对抗EGFR药物产生耐药性;因此,帕尼单抗仅限于治疗RAS野生型(WT)肿瘤。涵盖领域:本综述探讨了关于帕尼单抗的现有数据,并就抗EGFR疗效的预测标志物提出了新观点,包括原发肿瘤部位和BRAF突变。涵盖的其他细节包括帕尼单抗的作用机制、药代动力学、药效动力学和治疗的安全性方面,以及继发性耐药机制和不同治疗背景下的未来治疗前景。专家观点:帕尼单抗显著增加了RAS WT mCRC的治疗手段。在确定帕尼单抗疗效的预测生物标志物方面所做的努力对mCRC患者的分子选择发展至关重要。然而,原发性和继发性耐药仍然是重要问题。目前正在开展克服这些问题的新策略,取得了有希望的结果,这突出了帕尼单抗未来与其他靶向药物联合使用的潜力。