Continued from part 1
Dr. West: You have a huge portion of your patients who have an EGFR mutation and we know that over time patients develop acquired resistance. So how do you approach the patients who have a great response initially, have a known EGFR mutation, and then you see that slipping away at slow progression? Do you continue the EGFR inhibitor? Do you add something to it? Do you change the dose? How do you approach that?
Dr. Mok: I think this is one area where we still have a lot to learn. First of all, let’s define resistance, or progression. If you use the Jackman criteria (Jackman, J Clin Oncol 2010), that still incorporates the RECIST criteria, which mean if the lesion that has increased by about 30%, then it’s progression. But then one factor we didn’t look into was in the rate of progression within this definition. The second concern is about the occurrence of a new lesion that’s also progression. Now, whether this is directly applicable to a targeted like Tarceva or another EGFR TKI or not, I have some doubts, because simply from your experience and my experience, some of these patients get a new nodule, but they can take a long time to grow and the patient lives a normal life. And we also know the fact that if we take them off the TKI, the disease can progress rapidly. So some of these are slow progressors, then we just keep them on a TKI. Continue reading
A few weeks ago I had the chance to speak with Dr. Tony Mok, who is a professor in the Department of Clinical Oncology at the Prince of Wales Hospital in Hong Kong and the Chairman of the Hong Kong Cancer Therapy Society.
He is also the principal investigator and lead author for the pivotal Iressa Pan ASian Study (IPASS), which was published in the New England Journal of Medicine in the fall of 2009. I started by telling him that I consider that study to be arguably the most influential over the last 5-10 years in the field of lung cancer, because it highlighted that molecular predictive factors trump clinical markers in determining who is likely to do best with a targeted therapy, specifically an EGFR tyrosine kinase inhibitor like Iressa (gefitinib) or Tarceva (erlotinib). Here’s the first part of our conversation about what we’ve learned about how best to use these EGFR inhibitors and the potential differences in practice between Asia and the US.
The third and last podcast from our discussions with Dr. Lecia Sequist, of Massachusetts General Hospital and Harvard Medical School, covers the question & answer session that followed her excellent webinar on acquired resistance to EGFR tyrosine kinase inhibitors, as well as the update I did with her on the latest information from their experience of re-biopsying lung tumors over the course of treatment.
Here are the audio and video versions of the podcast, as well as the transcript.
EGFR stands for epidermal growth factor receptor, which is a molecule on the surface of many cancer cells that can be activated to activate signals that promote cell growth and cell division. Though this target may play a role for many kinds of cancer, non-small cell lung cancer (NSCLC) is one type in which this target protein is seen in a majority of people’s cancers. In a minority (about 10% in North America and Europe, but closer to 20-30% in Asian populations) who typically have little or no history of smoking and have an adenocarcinoma subtype of NSCLC, there is a particular mutation that leads to activation of the receptor and the downstream cascade of cellular activity that appears to often do a large part of driving the cancer mechanism. Consequently, drugs that block the EGFR target, specifically oral drugs that inhibit the tyrosine kinase portion on the back end, intracellular (within the cell) portion of the receptor (EGFR tyrosine kinase inhibitors, or TKIs, with examples being Tarceva (erlotinib) and Iressa (gefitinib) can sometimes lead to dramatic and long lasting tumor shrinkage. In a larger proportion of patients with NSCLC, these agents can provide a more modest benefit, consistent with the concept that the EGFR pathway is a contributing pathway for the cancer but not the primary driving force.