As I mentioned in a previous post, we have very little direct evidence of how chemo performs in advanced BAC, although it is generally perceived to be less effective in BAC than in other types of NSCLC.  The only trials that uniformly treated BAC patients with chemo used taxol (abstract by Scagliotti here, mine here) and had results that did not inspire us to want to move ahead with single-agent taxol in advanced BAC.

   Alimta/pemetrexed is a novel multitargeted antifolate, hence the mta at the end of its name.  It inhibits at least 3 important enzymes that are part of folate metabolism, and also generation of purines and pyrimidines, the building blocks of DNA.  It was initially approved by the FDA in combination with cisplatin for treating malignant pleural mesothelioma, which is a cancer of the lining around the lung.  Two years ago, it was approved by the FDA for treating advanced NSCLC in the second-line setting, after it was shown to have essentially the same clinical activity as taxotere in previously treated NSCLC but a bit less toxicity, primarily from blood counts not dropping as much, so less need for transfusions or risk for febrile neutropenia (fevers with low blood counts, which is usually treated with hospitalization for IV antibiotics).  It is currently one of the most commonly used second-line treatments for lung cancer, but this trial across the US is the first time it’s being looked at particularly in BAC.

   Why study it in BAC?  Like mesothelioma cells, BAC tumor cells have high levels of the receptors that alimta works through, known as the alpha-folate receptor; in fact, while adenocarcinomas seem to have high levels, the highest levels are in BAC.  Test tube studies also show that BAC tumor cells are very sensitive to alimta in these preclinical models.  These models also showed that the cells with the most expression of these receptors were also most sensitive to alimta.  Perhaps more importantly, there have been several cases of patients with advanced BAC who have had very nice responses to alimta, including some who had already progressed on EGFR inhibitors. 

    The SWOG 0526 trial will enroll 99 patients with advanced BAC or adenocarcinoma with BAC features who have had either no prior treatment or one prior therapy, which could be either chemo or an EGFR inhibitor (most likely Tarceva these days).  The trial will assess the results separately for patients who have previously received an EGFR tyrosine kinase inhibitor and those who have not.  The trial, by Principal Investigator Angela Davies at UC Davis in Sacramento along with co-chair Helen Ross in Portland, opened a few months ago and is now available at multiple institutions, listed if you hit the button at the bottom of the page for this link:

http://www.swog.org/Visitors/ViewProtocolDetails.asp?ProtocolID=2027

  Alimta is commercially available, and the treatment is the same dose and schedule as is routinely used for second-line treatment of NSCLC.  It is certainly possible to do this same treatment without enrolling on the trial.   But we’ll only be able to move BAC options forward by putting results together and looking at results for groups, rather than one patient at a time.  So if you’re interested and eligible, please check whether there’s a participating center near you and consider joining in the effort.