I'll get back to the storyline of our growing understanding of the differences of individuals based on pharmacogenomics very soon. But I wanted to give people some breaking news that just came out.

While the differences in anticipated clinical benefits from EGFR tyrosine kinase inhibitors like tarceva and iressa are well known (summarized in prior post), less well appreciated is the potentially significant differences in results with garden variety standard chemotherapy.

The issue of population-based differences in response to lung cancer treatments was essentially introduced with the EGFR inhibitors, so it’s appropriate to introduce racial differences overall with this work. Mention of more favorable results with EGFR inhibitors iressa and tarceva emerged with the earliest clinical studies and have since become a well established truism. Let’s explore what we know now and how we got here.

People who have been following my comments know that I am often questioning the wisdom of surgery in patients who don't fit the usual criteria for resection, which is most commonly pursued in stage I and II NSCLC and is often considered an option for some patients with stage IIIA NSCLC. To provide a very quick review of NSCLC staging, it's a combination of three factors:

1) Tumor (T) stage -- from 1 to 4, going from smallest and easiest to remove to hardest or largest to remove

2) Node (N) stage -- from 0 to 3, going from none to further distances from the main tumor

Member Sandra recently asked the question that several other people have asked in one form or another: how do we choose among the treatment options for second line therapy in NSCLC. I've covered in several posts and a huge number of responses in the Q&A Forum the leading options we generally consider for second line therapy for NSCLC.

In the Q&A forums recently, members Jianming and Neil introduced us to the novel agent XL647, in clinical trials now, but I figured it was worth me collecting more background and providing a more thorough background. XL647 is an oral small molecular that inhibits multiple tyrosine kinases, receptors on cells that trigger cascades of activity in the cells, thereby leading to tumor development and growth.

One of the successful examples of incorporating patient-reported outcome (PRO) measures into an important clinical trial was in the NCI-Canada study BR.21 (abstract here). This study assigned patients to either tarceva or placebo in a 2:1 randomization to the active drug:

I've described in a prior post and many of my comments here how tarceva and iressa, oral targeted therapies against EGFR, have been pretty consistently impressive in never-smokers. Not infallibly great, but these agents have shown high response rates in the 25-50% range for never-smokers, and have also been pretty favorable for remote and minimal smokers.

Intuitively, you'd think that people who are doing worse while getting treated for lung cancer are not going to do as well as people who have improvement in their symptoms after treatment starts. But how much do patient symptoms count in our current medical system for deciding whether a treatment is working or not, and when to move to a new therapy? The answer is that patient reported symptoms don't have a clear role yet.

There's a website called Adjuvant! Online, developed by oncologist Peter Ravdin, that is best known for its use after surgery for breast cancer in assessing the value of post-operative chemo. Because I don't really treat breast cancer, I haven't spent time on the website, but I do know that it's a valued resource among practicing oncologists who care for patients with breast cancer.