Dr. Geoffrey Oxnard, Dana Farber Cancer Institute, describes a wide range of options for best managing patients with advanced NSCLC who experience acquired resistance, the progression of cancer after a good initial response to a targeted therapy.

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Dr. Ravi Salgia from University of Chicago explains his approach to management of acquired resistance to a targeted therapy for advanced NSCLC, both in the setting of a single area of progression and also when disease progression is more diffuse.

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Dr. Heather Wakelee from Stanford University discusses the open question of whether patients with resectable or locally advanced NSCLC should have testing for molecular markers, as well as how we might use this information in clinical practice.

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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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Here I briefly discuss a challenging case of a patient who has an exon 20 mutation in the EGFR gene, which isn't one of the mutation types associated with a high probability of responding well to an oral EGFR inhibitor.  I cover the approach I favored and also some limited information that has just emerged to help clarify what we might expect for patients with an uncommon to rare variant  of an EGFR mutation (~5% of mutations detected).

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I hope it's interesting and helpful.  As always, I welcome your comments and questions.

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.

Here is Dr. Neal's summary from the ASCO 2012 Lung Cancer Highlights program of the SELECT Trial, which he led and presented, of adjuvant (post-operative) Tarceva (erlotinib) for patients with resected early stage EGFR mutation-positive NSCLC.

The response of cancers with a specific driver mutation , such as an EGFR mutation or ALK rearrangement, to a targeted inhibitor of that target, is often dramatic and long-lasting, but it is also almost always limited in duration, typically lasting several months or a few years.  Beyond that point, we tend to see a subset of the cancer cells become resistant progress, perhaps manifested as one or several  new lesions or growth of one area against a background of most of the remainder of the cancer still being well-controlled.  

In my last post, I described the concept of treating with a targeted therapy like an EGFR tyrosine kinase inhibitor (TKI) or ALK inhibitor at the time of acquired resistance.