Here's a continuation of the webinar content by Dr. Lecia Sequist, who is an Assistant Professor of Medicine at Harvard Medical School and Massachusetts General Hospital (MGH).

We've already discussed prior work on Met as a potentially valuable target in NSCLC, as illustrated by work with ARQ-197 combined with the EGFR inhibitor Tarceva (erlotinib) has demonstrated encouraging early results.

LM is a 73 year old patient of mine. She typifies the idea of functional age over chronologic age —physiologically, she’s more like a 50 year-old and remains extremely active despite having had lung cancer since the spring of 2006. The targeted therapy Tarceva (erlotinib) was her first treatment, which worked for over two years. She was then treated with three different cytotoxic chemotherapy regimens, with a theme of response followed by progression.

Hi again! You can think of this as a companion piece to my last post, examining some recent (but admittedly preliminary) evidence suggesting that Iressa (gefitinib) and Tarceva (erlotinib) may not be equivalent for patients with differing types of EGFR mutations. This is a slightly different topic, but one that has been quite contentious for several years: do KRAS mutations, found in 20% or more of patients with NSCLC, identify a group of patients who are resistant to EGFR inhibitors?

We know that cancer cells mutate over time -- in fact, that's how they became cancer cells. In fact, oncologists see the heterogeneity of cancer cells in our daily practice every day. Although there are certainly many reasons why patients have some of their cancer cells respond and others not (blood supply, local microenvironmental factors, etc.), one of the important factors is genetic heterogeneity within the cancer cell population -- some cells die and others don't.

Tarceva and Iressa (some of you may remember this drugs from a few years ago) have certainly become popular drugs for treating lung cancer, specially in the adenocarcinoma type of lung cancer. Drs. Pennell and West have discussed tarceva in other posts on this website – how it works, who benefits the most, what is the impact of certain mutations on the effect of the drug. Unfortunately, we are also too well familiar with the fact that these drugs don’t work forever and the cancer relapses even after having initially responded well.

Mrs. M was a 46 year-old woman who, despite having never smoked, was diagnosed with metastatic adenocarcinoma of the lung. She had a nice initial response to chemotherapy, and when she eventually progressed, she was treated with Iressa (an EGFR inhibitor similar to Tarceva which is no longer available in the US). To both her and her doctor’s delight, she had near resolution of her lung mass and most of her liver lesions after 2 months on Iressa. Unfortunately, after remaining stable for 10 months, her restaging CT scan showed one lesion in the liver was growing.

Most of the focus on predicting response to EGFR inhibitors has been on identifing molecular markers that are associated with major response to this kind of treatment. But we know that there is a group of patients who get no benefit from these expensive drugs, and in these patients, EGFR inhibitors would just lead to side effects and keep them from a potentially more effective therapy for them.