Lung cancer is the leading cause of cancer death among men and women worldwide, accounting for 12% of all new cancers and 18% of cancer deaths. Non-small cell lung cancer (NSCLC), including the histological subtypes of squamous cell, large cell, and adenocarcinoma accounts for about 85% of this group.
Clearly, chemotherapy not only remains the backbone of treatment for advanced NSCLC, but recently has also been integrated in the multimodality therapy of early NSCLC as preoperative or postoperative chemotherapy and as chemoradiotherapy. First-line treatment of advanced NSCLC in patients with a performance status (PS) of 0 to 1 consists of platinum-based doublets that include taxanes, vinca alkaloid, gemcitabine, and pemetrexed.
There is no universal consensus regarding the accepted chemotherapy standard of care. Whereas cisplatin/gemcitabine or cisplatin/vinorelbine is commonly used as the standard regimen in Europe and other parts of the world, carboplatin/paclitaxel appears to be preferred in the United States. The situation for nonsquamous NSCLC has recently changed with pemetrexed platinum now the preferred regimen in many countries. Other combinations that offer significant improvement over existing treatment strategies are urgently needed. Fortunately, advances in the understanding of biology and pathogenesis of lung cancer have occurred in recent years. This has permitted the development of a number of agents that selectively inhibit tumor-specific biological targets. It is hoped that these agents only further improve outcome of early and advanced NSCLC. The epidermal growth factor receptor (EGFR) is one of the potential targets of the medical treatment of NSCLC; its overexpression has been found in 40 to 80% of NSCLC tumors.
In advanced disease, standard doublet chemotherapy clearly has reached an efficacy plateau and offers only moderate benefit to the great majority of patients. One option under consideration to significantly extend survival has been the addition of targeted therapeutic agents to chemotherapy. The monoclonal antibody cetuximab is a unique EGFR inhibitor with significant efficacy in colorectal and head and neck cancer. It has been extensively investigated in combination with chemotherapy and radiation in NSCLC.
Several large randomized trials and meta-analyses have documented that cetuximab significantly extends survival in all histological subtypes and tumors immunohistochemically expressing EGFR. The greatest benefit of adding cetuximab to chemotherapy has been observed in Caucasian patients, patients developing skin rash during the first cycle of cetuximab therapy, and in tumors of patients with immunohistochemically high EGFR expression (immune score ≥200).
Cetuximab has improved the therapeutic index when combined with standard chemotherapeutic agents and radiation and has been approved for the treatment of metastatic colorectal cancer and head and neck cancer in combination with chemotherapy and radiation. Cetuximab has also been clinically investigated in a broad phase I-III program combining the EGFR antibody with a variety of cytotoxic agents and radiotherapy to define efficacy and the toxicity profiles in locally advanced and metastatic NSCLC.