Dr. Greg Riely from Memorial Sloan-Kettering reviews strategies for managing acquired resistance to EGFR inhibitors and other targeted therapies in advanced non-small cell lung cancer.

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Dr. David Spigel from Sarah Cannon Cancer Center offers his perspective on the agents he feels most likely to become clinical tools against lung cancer over the next few years.

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The question of how best to manage "acquired resistance" to a targeted therapy like an EGFR or ALK inhibitor in someone who has had a great response for a long time can be complicated and really doesn't have a best answer.  However, other doctors and many patients here and in the brick and mortar world ask me about how I approach it, and I've got some real opinions about it.  I'll qualify my further comments by saying that my own views have evolved over the years as we've gained more information as we get more clinical data and practical experience.

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.

Since we've come to appreciate the presence of distinct activating EGFR mutations associated with a very high probability of responding to an oral EGFR inhibitor, the question has emerged about whether there are significant differences in outcomes between the two most common ones, which are a deletion in exon 19 and a "

Here's the first of a series of posts on key presentations on lung cancer from ASCO 2010, as reviewed by myself and Dr. Nate Pennell of our faculty here several weeks ago. The first topic we covered was the very interesting if troubling Canadian BR.19 trial of post-operative Iressa (gefitinib) vs. placebo, as summarized by Dr. Pennell. Dr.

For the last several years, we've known that never-smokers are more likely to have a significant and long-lasting response to EGFR inhibitors. Since then, we've learned that EGFR mutation status is quite correlated with smoking status and is the more important, likely driving factor, but all of this work has led to a new focus on never-smokers and smoking history in general.

Shortly after ASCO 2009, Dr. Pennell provided the highlights of the early report of the SATURN trial, conducted primarily in Europe, that randomized patients to maintenance tarceva (erlotinib) or placebo after four cycles of first line chemotherapy. The early report described a modest but statistically significant improvement in progression-free survival (PFS), but overall survival (OS) wasn't reported at ASCO.

At ASCO a little over a month ago we learned the preliminary results of the SATURN trial that compared "maintenance" Tarceva (erlotinib), the oral EGFR inhibitor, to an oral placebo in patients who showed no progression after four cycles of first line chemotherapy.