While there have been new agents introduced and rapidly changing standards in advanced NSCLC, another 40% of patients with NSCLC have locally advanced (stage III) NSCLC, many of whom with disease that is not resectable but is potentially curable with agressive chemo and radiation. Last year's ASCO meeting included results that strongly suggested that consolidation taxotere after 6-7 weeks of concurrent chemo and radiation may not add a benefit, and in an important trial by the Hoosier Oncology Group (affectionately known as the HOG), the best treatment was with just two cycles of cisplatin/etoposide chemotherapy along with radiation (as detailed in a prior post).

Many oncologists, myself included, have been reluctant to accept that just two cycles of chemo and seven weeks radiation are really enough to treat stage IIIB disease, which is clearly more of a threat than stage II NSCLC, for instance, and for which we standardly give four cycles of platinum-based chemo. Most US-based oncologists give either two cycles of cisplatin/etoposide with concurrent chest radiation, or weekly low-dose carboplatin/taxol for about 7 weeks while a patient is getting radiation, and it's a bit unsettling to think that either there aren't potential improvements to be made by adding new agents, either to replace some of our older standards or to add along with the chemo/radiation concurrently or as a different consolidation therapy. Cisplatin/etoposide/RT has been used now for both limited SCLC and locally advanced NSCLC for 20 years, so we're all impatient to see new agents take their place and define some new standards.

A couple of interesting trials that integrated some of these newer agents were presented at ASCO this year. The first was done by the Radiation Therapy Oncology Group (RTOG) and presented by my friend George Blumenschein from MD Anderson Cancer Center in Houston (abstract here). This study was built on the alternative standard approach (to cisplatin/etoposide) of low-dose weekly carbo/taxol concurrent with radiation, which is sometimes preceded or followed by "full dose" chemotherapy to treat micrometastatic disease in other parts of the body more effectively, because we believe that the low dose weekly carbo/taxol primarily helps make the radiation work better but doesn't have much of an anticancer effect on other cells in the body. So this study, known as RTOG 0324, tested the activity and feasiblity of adding weekly erbitux, the targeted therapy and monoclonal antibody against EGFR with some evidence for activity in metastatic NSCLC (prior post here), along with concurrent carbo/taxol/radiation and then along with an additional two cycles of full dose carbo/taxol after the radiation portion was completed. The trial enrolled 84 patients with unresectable locally advanced NSCLC, with a design and highlights as shown here:

This relatively small test was primarily a test of feasibility of giving this regimen and testing whether it merits further development in larger trials. The investigators noted that the median survival of 22.7 months was the best that the RTOG has seen in this setting, although it's not particularly different from the HOG results with just cisplatin/etoposide/radiation, and no fancy new targeted therapy added. The side effects we always see with concurrent chemo and radiation, primarily esophagitis (inflammation of the esophagus) and pneumonitis (inflammation of the lungs) were well within the typical range for the regimens we use routinely, although the group did report 5 patient deaths attributed to the treatment, from a variety of causes. While concerning, this 6% death rate from treatment is right in the same range that SWOG and HOG have seen with aggressive treatment, reminding us that our treatments for locally advanced NSCLC can be so challenging that they can be a competing survival threat along with the cancer itself. Based on the encouraging results overall, the RTOG is adding erbitux to their current question of testing higher vs. lower dose radation. Here's what they're trying to make their new trial look like:

So this trial should give us information about whether we should raise the dose of radiation and whether we should add erbitux to the mix.

Next we'll cover a trial that introduces alimta into the stage III NSCLC setting, along with erbitux.