Single-Agent Erbitux Studies in NSCLC

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December 15, 2006 - 5:58 pm email to a friend printer friendly view / write comments

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Dr. West

   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. 

   Tom Lynch from Massachusetts General Hospital in Boston, who helped identify the EGFR mutation in 2004, presented the first single-agent erbitux results in NSCLC, in 2004 (abstract here).  He described a total of 33 patients with previously treated (chemo, not EGFR inhibitor) advanced NSCLC.  All patients were treated with weekly IV erbitux, with cycles defined as a four week period.  He found that 2 patients responded, and the total “disease control” rate, which is responses and stable disease together, was 27%.  Reasonable, not particuarly remarkable.  All of these patients were positive for EGFR by immunohistochemistry (abbreviated as IHC, it means staining of the EGFR protein on tumor cells, which is not very clearly associated with doing well or poorly on EGFR inhibitors like iressa and tarceva).  Interestingly, neither of the patients who had significant tumor shrinkage had an EGFR mutation, which is found in the part of the EGFR molecule on the inside of the cell that iressa and tarceva block, called the tyrosine kinase portion.  So EGFR monoclonal antibody activity isn’t necessarily associated with the EGFR mutations we’ve often seen in major iressa or tarceva responders.  The side effects were pretty much as expected, primarily rash, fatigue, and nausea/vomiting.

   The longer follow-up on this work (abstract here), with twice as many patients, was presented by Dr. Rogerio Lilenbaum, our friend and a real lung cancer expert in Miami, who has been mentioned in some prior posts.  Almost all (60 of 66) of the patients had EGFR positive tumors by IHC, the median age was 63, and two thirds of the patients were men.  The results were about the same as previously, with a response rate of only 4.5%, and about 35% with at least stable disease.  About 42% of the patients on the trial were alive a year after starting the trial, and one patient was on it without progression for 22 months and counting when the results were reported.  Tissue was available for two of the 3 responders, neither of whom had an EGFR mutation, while the three patients found to have a mutation did not respond to erbitux.  Rash, fatigue/malaise, nausea/vomiting, infusion reactions, and mouth sores (stomatitis) were the most common side effects.

  Sadly, that’s pretty much what we know about erbitux as a single-agent in advanced NSCLC right now.  This work didn’t generate a lot of excitement, but it did suggest that the people who respond to the oral EGFR TKIs aren’t necessarily the same people who may respond to IV EGFR monoclonal antibodies.  Because of that, one of the potential ideas for managing patients who respond very well initially to EGFR TKIs and then show slow progression after a prolonged response is to add an agent like erbitux, or possibly avastin, to the EGFR TKI.  But in the meantime, the results with single-agent erbitux haven’t been impressive enough to move ahead in larger trials.

Posted in: EGFR mutations and other molecular markers, Epidermal growth factor receptor (EGFR)-based therapies, Lung Cancer, Second-line treatment, Stage IV/Advanced/Metastatic NSCLC, Targeted therapies, Third-line therapy and beyond                     email to a friend printer friendly