Yesterday I reviewed a series of studies of the EGFR monoclonal antibody cetixumab, or Erbitux, combined with chemotherapy. Overall, these trials are modestly encouraging, without what I would consider to be a potential antagonistic effect when chemo and EGFR tyrosine kinase inhibitors (TKIs) like Iressa or Tarceva. However, we still don't have studies big enough to establish any role for erbitux. Today, I'll cover the very limited experience of single-agent Erbitux in advanced NSCLC.

In my last post, I described the somewhat disappointing results for tarceva compared with chemotherapy in a trial of unselected advanced NSCLC patients with a marginal performance status. However, EGFR tyrosine kinase inhibitors like iressa and tarceva were developed as targeted therapies, so perhaps they might prove to be more effective if used selectively, in a targeted population.

The emergence of targeted therapies provides a goal of treating the cancer more selectively, thereby minimizing side effects, while hopefully achieving results as good as or better than standard chemotherapy. Although this is important in the entire population of cancer patients, this is a particularly welcome benefit in patients who may be reluctant to or not healthy enough to receive standard chemotherapy.

I reviewed some of the differences in the biology and clinical behavior of never-smoker lung cancers vs. the much more common lung cancer seen in current or former smokers. The main reason it is worth discussing is that there appear to be important differences in how never-smokers with NSCLC respond to some treatments, particularly EGFR tyrosine inhibitors like Tarceva, or Iressa previously.

In a recent post, I described the approval of taxotere as a second-line chemotherapy with a modest but survival benefit for patients previously treated with one line of chemo, usually a platinum-based doublet.

As described in a prior post, chemotherapy after surgery is often recommended after surgery, at least for a subset of patients with stage IB to IIIA (without mediastinal lymph node involvement) NSCLC, based on a potential to increase cure long-term survival compared to surgery alone.

Thus far, the vast majority of patients who have an initial response to EGFR tyrosine kinase inhibitors like Iressa and Tarceva will eventually become resistant to them.