Several weeks ago, we were fortunate enough to be joined by not one but two international stars in lung cancer research that is being translated directly from lab bench to bedside of the patient. I don't think there's a more clear and inspiring example of good science leading to effective therapy, albeit for a limited patient population, than the story of the anaplastic lymphoma kinase (ALK) inhibitor crizotinib (recently FDA approved and commercially launched as XALKORI) for patients with an EML4-ALK rearrangement (approximately 4% of the broader NSCLC population). Drs.

It has become a common topic of conversation on this site (and in the lung cancer community at large) to discuss mutations in the epidermal growth factor receptor (EGFR). However, since we frequently throw out the terms “deletion 19 mutation”, “L858R”, and “T790M”, I thought would be worthwhile to explain a little bit about the different EGFR mutations and what we know about their clinical significance.

Back when I first started doing this, one of my earliest posts (see here) was on the question of whether EGFR tyrosine kinase inhibitors (TKIs) (see introduction to this work in prior post).

One of the basic concepts of oncology is that you treat patients with different drugs once they've shown progression on a treatment, rather than continue that a patient has presumably become resistant to. However, there are some exceptions to this: many or most women with breast cancer continue the antibody herceptin (trastuzumab) even after progression, adding it to one chemo and then the next, and the same is often done with avastin in colon cancer and sometimes lung cancer as well.

We've seen clear evidence that patients who have tumors with certain mutations in the EGFR gene are highly likely to respond to oral EGFR inhibitors like tarceva (erlotinib) or iressa (gefitinib) -- with response rates that are in the 70% range and often last for many months or even a few years (see prior post).

A quick point on the importance of biology over treatment. Years ago, I highlighted the results in the TRIBUTE trial of chemo with placebo or combined with erlotinib (tarceva) at the same time (biomarker study abstract here), which showed that patients with EGFR mutations had a much better survival whether they received an EGFR inhibitor or not:

One of my good friends in the lung cancer community, Dr. Ed Kim from MD Anderson, was in town tonight and gave a talk that I attended.

Actually, it's some background information and your blood that's needed.

I just recently wrote a post (here) that describes how I became convinced that under certain circumstances there could be a genuine value in determining whether a particular lung cancer patient has a tumor with an EGFR activating mutation.

Those who have followed my writings over time will know that I haven’t been inclined to adopt a reflexive strategy of ordering molecular testing without good evidence that having this information will improve outcomes. Testing tumors for EGFR mutations is advocated by a vocal minority of lung cancer experts in Boston and New York City, but this hasn’t been advocated by the broader lung cancer community yet, or adopted as routine clinical practice.