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.

One of the current controversies in the field of lung cancer is whether we should be doing biopsies routinely when a patient develops progression of their disease, particularly in the setting of acquired resistance to a molecularly targeted therapy.  There are some academic oncologists who favor this approach, but I think there's a very good reason why this isn't and shouldn't be the current standard of care.

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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.  

One of the questions that comes up fairly frequently is what to make of a "mixed response" to systemic therapy: after several weeks or months of treatment, a scan shows some areas of known disease shrinking, but others are growing.  Why might this happen? What does it mean? And what should it lead us to do?

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.

Introduction

Thank you to member Craig for asking some excellent questions in response to my Highlights of 2011 webinar.  Thank you also to Dr. West, who emailed me to comment more on the idea of radiation for cells with acquired resistance.

We’ve spoken at length about EGFR and related mutations such as EML4/ALK and ROS1 on GRACE.  For those who are not familiar with these subjects, I will refer you to my webinar for a summary on the most recent data on EGFR, EML4/ALK and ROS1:

Here's the final piece of the webinar with our own Dr. Jared Weiss on Highlights in Lung Cancer from 2011 -- the question and answer session that followed his presentation.  Below is the transcript, figures, and the audio and video versions of the podcast.

Apologies for the long wait since our own Dr. Weiss's upbeat and thoughtful review of the leading stories about lung cancer in 2011.  Dr. Weiss covered a lot of ground in his presentation that was followed by a Q&A session, so we've broken that up into several short pieces that cover a few highlights at a time.

Continuing Dr. West's theme discussing new therapies for patients with acquired resistance, I'd like to answer a few questions about HSP 90 inhibitors that have caught my attention on GRACE over the past few weeks, and in particular, highlight my "pet" targeted agent, AUY922. HSP 90 inhibitors are drugs that many of you already know about-they are being studied in patients with ALK(+)lung cancer and as a 2^nd line therapy option for all patients with lung cancer with Taxotere.