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Acquired Resistance to EGFR Tyrosine Kinase Inhibitor Therap

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Acquired Resistance to EGFR Tyrosine Kinase Inhibitor Therapy: Multiple Experts Weigh In

http://blog.lungevity.org/2011/12/20/ac ... o-egfr-tk/

December 20th, 2011 - by Dr. Jack West

Returning to the series of challenging cases in lung cancer I discussed with Drs. Jyoti Patel from Northwestern and Bob Doebele from University of Colorado earlier this year, we’ll now cover a difficult situation of the patient with advanced NSCLC who has an EGFR mutation, starts Tarceva (erlotinib), has a great response for over a year, then develops mild but clear progression. This is so called “acquired resistance” to an EGFR tyrosine kinase inhibitor (TKI), and it’s the scenario we face after essentially every good response to an EGFR TKI.

Following the comments by Drs. Patel and Doebele, you’ll then hear the impressions of five more terrific lung cancer experts: Dr. Suresh Ramalingam from Emory University in Atlanta, Dr. Jonathan Goldman from Premiere Oncology in Santa Monica, Dr. Julie Brahmer from Johns Hopkins University in Baltimore, Dr. Heather Wakelee from Stanford University in Palo Alto, CA, and Dr. Karen Reckamp from City of Hope in Duarte, CA). Each will offer their own thoughts on the same scenario, so you can understand where our principles converge and also where the recommendations are just more more of an individualized judgment.

In this case, they cover the key questions that come up over and over for acquired resistance to an EGFR TKI: Should we continue for a while on the EGFR TKI without making any changes? When we do ultimately determine that it’s time to make a change, what should it be? Do we stop the EGFR TKI, or do we continue it and add a chemotherapy-based regimen as well? Does it help to “re-challenge” a patient with an EGFR TKI again if we stop it? And at that point of acquired resistance, how valuable is it to do a repeat biopsy? Is this just an arguably a nice thing to consider or an approach that the experts would clearly pursue?

Click on the blog link above to find the audio and video podcasts of this program (same program, just different formats), and also the transcript and figures. That said, this program isn’t very video-oriented, so you won’t miss much by concentrating on the audio and/or the transcript.

Folks interested in this topic may also want to check the podcasts from our prior discussions with Dr. Lecia Sequist of Massachusetts General Hospital. She spoke with us in early 2011 about what we know and are still learning about acquired resistance to EGFR TKIs, and then we did a follow-up discussion of the potential insights we might glean from repeat biopsies in this setting.

I hope you find this program both interesting and helpful, even though we don’t arrive at clear answers to these hard questions.

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