The American Society of Clinical Oncologists is currently holding their annual meeting so there have been a couple of interesting to studies come out of it. The first one has been plastered all over the news. It's an interesting example of where a bit of luck is involved in the drug development process.
Pfizer had been developing this compound for cancer that inhibited a particular protein called C-met. It was also known to inhibit another protein dubbed Anaplastic Lymphoma Kinase but they didn't think that part important. Let's just call it ALK for short. Along comes a study out of Japan which shows that a small percentage of the lung cancer population has a mutation in ALK. Oops, I guess that part may be important. Pfizer recognizes the opportunity and begins to recruit lung cancer patients with this mutation which occurs in about 3-5% of the non-small cell lung cancer population (NSCLC). They presented the Phase I results. Keep in mind that Phase I results are usually about safety. Any hint of efficacy, especially in cancer is like icing on the cake.
82 patients ended up taking the pill twice a day. The patients tended to be younger (50s versus the typical 70s), never or light smokers, and had already failed at least 2 different chemotherapies. Of those 82 people, nearly 90% had their tumor either shrink or hold steady. That's impressive in a Phase I. That's impressive in this disease considering that a 15-20% response rate is the current going rate for initial treatment. I'm not sure what is in refractory cases like these. And to top it all off, the side effects were milder than chemo because it's a more targeted therapy. But with anything, here are my caveats:
- It's Phase I. Who knows if this can repeat this dramatically.
- It's Phase I. Who knows what happens with chronic treatment. Maybe there are nasty bleeding effects down the road.
- It only apppears to work in patients with this mutation. I'm not aware if there is any response in people without the mutations.
- I don't know if it matters for this treatment if the tumor is squamous cell or not.
- We don't know what the long term effects are on survival which is where the rubber meets the road in cancer.
Pfizer is already lining up the Phase III trial. I can't find anything on Clinicaltrials.gov but Pfizer's website has the criteria. The patient has to have failed a previous round of platinum based therapy. My brother hasn't done that so he wouldn't be eligible. The comparator group also involves pemetrexed which works only in non-squamous cell so that makes me wonder about the histological diagnosis more. Regardless, it's definitely on the top of my list to ask the doc during the next round of chemo in about three weeks. It may be of utility down the road as I suspect if these results are real, then this will hit drug status fairly quickly. Gleevec, another targeted molecular therapy that had impressive Phase I results like these, went from Phase I to bedside in about 3 years which is lightning fast.