A year ago, almost to the day, we presented an excellent podcast by Dr. Ross Camidge at the University of Colorado, describing the very new and promising work on the Pfizer investigational agent crizotinib for the subset (4-5% of patients with NSCLC) who have an ALK rearrangement. This story, although thus far limited to a minority of patients with lung cancer, was so promising that it was the subject of a presentation in the Plenary Session at ASCO and has since been published in the New England Journal of Medicine.

A lot has happened in that year since Dr. Camidge initially presented this work on crizotinib, and in fact it was at that time that he announced that the name crizotinib had just been assigned to this agent. Pfizer launched a pair of trials for ALK rearrangement-positive patients, one a randomized trial in the second line setting of either Alimta (pemetrexed) or Taxotere (docetaxel) vs. crizotinib, and the second a single arm trial for people more heavily treated, or those who were assigned to and progressed on chemo in the randomized trial with crizotinib, or some others who were otherwise ineligible for the randomized trial (which was meant to be the higher priority trial in getting to FDA approval). Very recently, however, Pfizer sent out a few terse memos noting that they would be filing with the FDA, phasing out the randomized trial (not closing it immediately), and keeping the single arm crizotinib trial open to provide it to ALK positive patients while we wait on the FDA.

Dr. Camidge was kind enough to offer me a more comprehensive update, including parts of presentations he has done recently, including at the European Society for Medical Oncology (ESMO) fall meeting in Milan.

First, we've got a little more follow up on the outcomes of the patients in the original, expanded phase I trial presented in preliminary fashion at ASCO, at it looks every bit as good. With 105 evaluable patients, the updated waterfall plot still looks extremely impressive, with a few at the far right showing 100% tumor shrinkage:

(click on image to enlarge)

With further follow-up, the median progression-free survival is 9.2 months, with more than 7 in 10 showig no evidence of progression after 6 months.

He also decscribed a clinical trial, Pfizer 1014, that is going to test crizotinib in the first line setting: randomization to cisplatin or carboplatin with Alimta, or crizotinib, for patients with an ALK rearrangement. He also went reviewed the plan of the randomized second line trial being phased out soon in the US, before the anticipated FDA approval, but continuing to accrue outside of the US, where crizotinib would likely not be widely commercially available. The single arm trial will remain open and will be expanded to permit crizotinib as a second line treatment. However, the clinical trials and FDA approval would be paired with a positive result on ALK testing being done through the central lab that is a collaborative effort between Abbott and Pfizer.

But last year I also described the problem of patients testing positive for an ALK rearrangement by various emerging new commercial tests but then testing negative for an ALK rearrangement through the central lab. These patients are not eligible for the larger Pfizer trials, but other investigators have also identified patients in this situation. They have actually been found to respond to crizotinib:

This is good to know, though troubling, because it makes it harder for patients in this situation to get crizotinib. The sites participating in the phase I trial are continuing to offer this trial as a mechanism for such patients to receive crizotinib, because testing positive at the central Abbott/Pfizer lab isn't an eligibility requirement for this trial. For the record, those places are:

• Dana Farber/Massachusetts General/Beth Israel, all in Boston
• Memorial Sloan-Kettering in New York
• University of Chicago
• University of Colorado in Denver
• University of California in Irvine
• Seoul National University in Seoul, Korea
• Peter MacCallum Cancer Centre, East Melbourne, Australia

So that's where things are right now, but it's changing all the time. I'll be attending a meeting just on targeted therapies in lung cancer in the next few weeks, so there may be some new information floating around there. In the meantime, big thanks to Dr. Camidge for going out of his way to get the message out to the lung cancer community!