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Is Rash a Good Thing with EGFR Inhibitors?
An acne-like rash or dry skin is a very common side effect of the drugs that target the epidermal growth factor receptor, with approximately 3/4 of patients who receive the EGFR tyrosine kinase inhbitor tarceva/erlotinib experiencing skin toxicity. Similar skin toxicities are also seen, but a bit less commonly, with the very similar drug iressa/gefitinib, and also frequently with erbitux/cetuximab, a monoclonal antibody that is less well studied in lung cancer. But since the earliest clinical trials of these agents, there have been questions of whether the rash is something more than just a potentially problematic side effect, but rather a marker of someone likely to do well with these agents.
Are EGFR Inhibitors Only Useful in Certain Patient Groups?
Since the earliest clinical trials of EGFR inhibitors in NSCLC, certain clinically defined patient subsets became identified as more likely to show a benefit than others. Such studies suggested that women, patients with adenocarcinomas rather than squamous cell carcinomas, Asian patients, and never-smokers compared with current or former smokers were the patients who would do well with EGFR tyrosine kinase inhibitors like gefitinib (Iressa) or erlotinib (Tarceva). Since that time, we have been debating whether these targeted therapies should be used primarily or exclusively in selected populations or whether they should be used in general lung cancer populations. The correlation of rash with better outcomes is another interesting issue that is a big enough topic I’ll discuss it separately in the near future. Since it’s not something you know about before you start treatment, unlike patient sex race or subtype of lung cancer, it’s a different issue.
EGFR Mutations and Acquired Resistance After Responding
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. At this year’s ASCO, our huge annual US-based oncology conference, a report was made by the group at Memorial Sloan Kettering Cancer Center (Riely abstract here) on a small series of patients who had progressed after a prolonged period of responding to Iressa or Tarceva. They found that patients who had slow progression, generally without symptoms, and then came off of their EGFR TKI therapy would often experience a rapid worsening of symptoms.
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