Yesterday afternoon, the FDA approved the ALK inhibitor crizotinib, newly christened as XALKORI, for patients with locally advanced or metastatic NSCLC who have an ALK rearrangement as identified by a particular central lab (test co-developed by Abbott and Pfizer, the makers of XALKORI). We've discussed the significant efficacy of XALKORI for this subset of NSCLC patients, with the frequency of an ALK rearrangement being somewhere in the range of 4-5%, and about 2/3 of ALK-positive patients showing significant tumor shrinkage on XALKORI, and more than 90% showing stable disease or tumor shrinkage. Moreover, these responses are of a duration typical of those we see with targeted EGFR-based therapies for patients with an EGFR mutation -- in the range of a year, in contrast with more typical chemotherapy-based responses for advanced NSCLC, which more commonly last for several months, at most. The fact that XALKORI is an orally available anti-cancer treatment with very mild side effects also adds to the appeal.

The biggest limitation, of course, is that 4-5% frequency of an ALK rearrangement, far more commonly seen in patients with an adenocarcinoma, little or no smoking history, and also apparently more prevalent in younger patients, men a little more commonly than women, and especially seen in patients with the unusual (and often more aggressive) NSCLC subtype of signet cell adenocarcinoma.

Dr. Ross Camidge, lung cancer expert at the University of Colorado and friend of GRACE (and me), has been working with crizotinib from its earliest clinical trials in patients. Click to get to his excellent presentation from early 2010 that describes the early development of this agent, and also a post with information he provided as an update. In addition, my TEDxOverlake talk from a couple of months ago discussed broader themes of the benefits of self-educated patients, centered around the impact of XALKORI for one remarkable patient.

The approval of XALKORI is one more important landmark in the development of "molecular oncology", as cancer care becomes defined by specific genetic alterations that can increasingly be treated by targeted therapies. Though we sometimes see efficacy of targeted therapies given to broad populations, we have seen a new category of efficacy when we give targeted therapies to targeted populations, such as an oral EGFR inhibitor to patients with an EGFR inhibitor, an antibody against HER2/neu for the subset of breast cancer patients with HER2 overexpression, and now ALK inhibitor therapy to the subset of patients with an ALK rearrangement.

The clinical trials testing XALKORI required testing of a wide range of patients to enroll a much smaller number. It was important to demonstrate that it's possible to develop new agents and conduct clinical trials for small subsets of patients, geographically dispersed all over. In many cases, patients were the drivers of their molecular testing, and they often needed to travel significant distances to participate in the research opportunities. But while so many other new treatment approaches aspired to only a small incremental benefit wouldn't have produced enough incentive to leave a patient's home state, the promise of a targeted therapy for a precisely targeted population is enough to get people flying to get access to such an agent.

Of course, that kind of activity comes at a price, and for XALKORI, it's $9600/month, which makes Tarceva seem like quite a bargain at $5000/month. The higher price point of XALKORI is presumably based on the following considerations:

1) XALKORI is likely to be far more effective for ALK-positive patients than Tarceva will be for the patients who don't have an EGFR mutation (about 85-90% of patients with advanced NSCLC in North America are EGFR wild type, meaning no mutation)

2) The market for XALKORI, limited by the FDA to the 4-5% of NSCLC patients with an ALK rearrangements, is only a small fraction of the market for Tarceva (pretty close to all patients with advanced NSCLC).

Thankfully, Pfizer is offering a patient assistance program for uninsured or underinsured patients, and a co-pay assistance program for patients who would be required to pay more than $100/month.

You can learn a few more details about availability and other practical issues from the FAQ (produced by Pfizer) below:

xalkori-faq

Finally, we'll be having our next webinar, likely in the last week of September, with Dr. Camidge and Dr. Ben Solomon from Melbourne, Australia, providing an overview of the development of XALKORI, the trials that led to its approval, how it will be used, and some future directions for the field. Details coming soon.