There's been a theme with the inhibitors of the epidermal growth factor receptor (EGFR) -- both oral tyrosine kinase inhibitors (TKIs) and IV monoclonal antibodies -- that the patients who demonstrate good results with these agents tend to get a rash, while the patients who don't get a rash do poorly.

The short answer is no. Since the introduction of the targeted agents that inhibit the epidermal growth factor receptor (EGFR), both the oral EGFR tyrosine kinase inhibitors (TKIs) like Iressa (gefitinib) or Tarceva (Erbitux), and the monoclonal antibody therapies against EGFR like Erbitux (cetuximab) have been identified as often having a rash as a leading side effect.

Completing our tour of clinical factors that we might use for predicting benefit with the EGFR monoclonal antibody Erbitux (cetuximab) in the FLEX trial is the development of a rash. We're actually discussing rash separately from the other clinical factors from the FLEX trial that we discussed in the prior post for a couple of reasons.

Erbitux (cetuximab) is a monoclonal antibody to EGFR, and it's actually made from a protein that is part mouse and part human (called a chimeric protein, named for the mythologic creature chimera that was composed of multiple parts from different animals). It's uncommon but not rare for patients to have an allergic reaction to this protein, and in most large national and international studies show rates of hypersensitivity reactions (HSRs) in the 1-3% range.

The improvement in median survival of 1.2 months with the monoclonal antibody to EGFR erbitux (cetuximab) in the FLEX trial that I've previously described was statistically significant, but there's plenty of room to debate whether it's really clinically significant (see prior post). What If we could add some way to refine our predictions of who will benefit from the addition of erbitux?

Though EGFR inhibitors like tarceva can produce some terrific and long-lasting results in many patients, they aren't toxicity-free. The "targeted therapies" we use just have a very different side effect profile from standard chemo, and the EGFR inhibitors are well known to have skin-related side effects as the leading problem, with loose stools/diarrhea as a less nearly ubiquitous second place issue.

One of my earliest posts when I started OncTalk was on the use of oral inhibitors of the epidermal growth factor receptor (EGFR), one of the growth signals that is often over-active in cancer cells, against advanced bronchioloalveolar carcinoma (BAC), a unique subtype of lung cancer that tends to grow within the lungs, sometimes slowly, and not progress elsewhere.

As I've described in a prior post, there is some evidence that patients who develop a rash on tarceva (erlotinib) have an improved survival compared to patients who experience no skin toxicity on tarceva. The key question is whether this is an issue of under-dosing some patients, or if it's just a correlate of overall immune function or constitution in a person, in which case increasing the dose won't improve the outcome.

There's a really helpful resource for patients, developed by several leading experts in EGFR-based therapy and specifically the very common skin toxicity associated with EGFR inhibitors like iressa, tarceva, erbitux, and some others.

Rashes from EGFR inhibitors: we like to see them, because we know that many trials have shown that skin toxicity on drugs like tarceva is associated with better survival (see prior post), but the fact is that sometimes a rash is more than an inconvenience and can really make people miserable, or at least pretty unhappy, as described in the comments and questions from a discussion forum thread today.