Summary statement: Novel agents in the treatment of lung cancer: Advances in epidermal growth factor receptor-targeted agents

The Third Cambridge Conference on Novel Agents in the Treatment of Lung Cancer was convened in Cambridge, Massachusetts on September 23 to 24, 2005 to discuss ongoing research into the significance of the epidermal growth factor receptor (EGFR) pathway in the biology of non – small cell lung cancer (NSCLC) and the potential for novel therapies targeting this pathway. The conference format combined brief presentations with extended periods of open discussion. The conclusions reached over the course of the 2-day conference are summarized briefly below and presented at greater length in the individual articles and accompanying discussions that comprise the conference proceedings. Clinicians who treat patients with NSCLC are aware that this is a highly heterogeneous disease. Until recently, we lacked the ability to use molecular profiles to classify patients into clinically meaningful subgroups, instead relying on classic histopathology and radiographic staging (Table 1). With the advent of targeted therapy and the discovery of a number of potential biological markers, such as sensitivity- and resistance-inferring mutations, and evaluation of gene copy number, it is becoming possible to define distinct patient populations. This hopefully will allow us to make predictions of treatment response and overall outcome. These recent advances have resulted from a collaborative effort of clinicians and researchers. Clinical observations have been central to stimulating investigations into the biological basis for the dramatic responses seen in a small number of patients treated with small-molecule EGFR tyrosine kinase inhibitors (TKIs), i.e., gefitinib and erlotinib. Overall, these two agents produce partial responses in 10% to 20% of patients with NSCLC. The primary focus of the conference was to address three questions. First, what is the optimal way to predict benefit from EGFR TKI therapy and thus to identify patients who might benefit from first-line or even adjuvant treatment? Next, given what we have learned about EGFR biology, what strategies or combination therapies can be tried to extend and prolong the efficacy of the EGFR TKIs? Finally, will new classes of agents with different mechanisms of receptor inhibition or multiple targets have activity in patients not responsive to the currently available EGFR TKIs as monotherapy? These newer agents include, among others, panitumumab, an anti-EGFR fully humanized monoclonal antibody; ZD6474, a dual inhibitor of EGFR and vascular endothelial growth factor receptor (VEGFR); and lapatinib and HKI 272, which are irreversible inhibitors of EGFR and HER2. Table 2 provides an overview of currently ongoing late-phase clinical trials of EGFR-targeted agents.