Continued from part 1

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.

Over the past several years, probably the biggest development in the field of NSCLC has been the recognition of the importance of molecularly-defined subgroups that help define the clinical patterns of how patients are likely to do with various treatments. We've seen this clearly illustrated with EGFR mutations vs.

Since we've come to appreciate the presence of distinct activating EGFR mutations associated with a very high probability of responding to an oral EGFR inhibitor, the question has emerged about whether there are significant differences in outcomes between the two most common ones, which are a deletion in exon 19 and a "

The negative trials don't get a lot of discussion, but the ZEPHYR trial, a phase III study that directly compared Zactima (vandetanib), an oral inhibitor of EGFR and angiogenesis, vs. placebo, was one that merits some follow-up after my reporting that it failed to show a survival benefit, which was essentially the only thing we learned about the trial prior to ASCO this year.

Here's the first of a series of posts on key presentations on lung cancer from ASCO 2010, as reviewed by myself and Dr. Nate Pennell of our faculty here several weeks ago.

The first topic we covered was the very interesting if troubling Canadian BR.19 trial of post-operative Iressa (gefitinib) vs. placebo, as summarized by Dr. Pennell.

Here's a podcast from the webinar presentation earlier this month by our beloved Dr. Weiss, covering the open question of whether we should consider giving an EGFR inhibitor like Tarceva (erlotinib) as an adjuvant (post-operative) therapy following potentially curative surgery for early stage NSCLC. It's a setting in which there is a good rationale if we extrapolate from the setting of metastatic NSCLC, at least for patients with an EGFR mutation, but we've made incorrect presumptions before when we extrapolate.

Perhaps the most unexpected clinical trial result in lung cancer over the past 5 years was the finding in the large Southwest Oncology Group (SWOG) 0023 trial that randomized several hundred patients to maintenance therapy with either the oral EGFR inhibitor Iressa (gefitinib) or a placebo after chemo/radiation concurrently and then consolidation taxotere (docetaxel).

What we are striving for in cancer care today is personalized medicine. So, if a patient with newly diagnosed NSCLC has an activating epidermal growth factor receptor (EGFR) mutation, we give that patient Tarceva (erlotinib), a tyrosine kinase inhibitor (TKI). Right? Well, yes -- but it doesn’t always work (the response rate is in the 70-75% range). Why not? We’re not sure, but it would be nice to learn why we don't see near a 100% response rate among patients with EGFR mutations, so that we can know to recommend other alternatives.

I would consider the recently published IPASS trial that compared Iressa (gefitinib) to standard chemo of carbo/taxol (paclitaxel) to be an extremely influential trial in lung cancer that has essentially ushered in a new era of molecularly-defined guidance of our treatment for many patients with advanced NSCLC, and we can expect that this is how we’ll be approaching a much broader population of lung cancer patients.