I reviewed a couple of presentations on bronchioloalveolar carcinoma (BAC) at ASCO 2007, including one by Cadranal and colleagues in which patients with advanced BAC received single agent Iressa (abstract here).

One of the themes that we've covered in some of the posts introducing the clinical entity of BAC is the variability in its natural history. In fact, much of what we've been learning about BAC has been in the last several years, and we're still learning more about it all the time. One of the things we've struggled with is the range of outcomes, that some patients can experience rapid deterioration and no response at all to EGFR inhibitors, while other patients can have a remarkably slow progression, and they sometimes will have an astounding regression of disease from EGFR inhibitors.

As I've described in a prior post, one of the most consistent findings in the work with the EGFR inhibitors Iressa (gefitinib) and Tarceva (erlotinib) is that never-smokers are far more likely to demonstrate a response and survival benefit than patients who do smoke or did smoke. Here, for instance, is the set of survival curves separated by smoking status for the large randomized trial of tarceva vs.

In most of the history of lung cancer management, we have been "lumpers" rather than "splitters", tossing together many different kinds of lung cancer together and presuming that they all respond similarly and should be treated similarly.

In light of a growing focus on the issue of lung cancer in never-smokers, it makes sense to try to identify potential causes in this population. Among the leading candidates as a cause of lung cancer in never-smokers is secondhand, or environmental tobacco smoke (ETS) exposure.

While lobectomy or pneumonectomy may be the surgical treatment of choice for most NSCLC tumors in younger, fit patients, a limited resection may be an ideal choice in certain settings. In my previous post I discussed the data supporting a limited resection in older patients, who are likely to have competing health risks that may make it less critical to pursue the most aggressive surgical strategy. Another situation in which a sub-lobar resection may be particularly appealing is when the tumor is quite small and/or has characteristics suggestive of an indolent natural history.

In my last post, I described the somewhat disappointing results for tarceva compared with chemotherapy in a trial of unselected advanced NSCLC patients with a marginal performance status. However, EGFR tyrosine kinase inhibitors like iressa and tarceva were developed as targeted therapies, so perhaps they might prove to be more effective if used selectively, in a targeted population.

The emergence of targeted therapies provides a goal of treating the cancer more selectively, thereby minimizing side effects, while hopefully achieving results as good as or better than standard chemotherapy. Although this is important in the entire population of cancer patients, this is a particularly welcome benefit in patients who may be reluctant to or not healthy enough to receive standard chemotherapy.

We know far too little about the best way to treat older patients with NSCLC, that lung cancer, like many other cancers, is a disease highly related to advanced age. First, how do we define an older, or elderly, population in cancer treatment terms? Beyond the joke that it increases as the person answering gets older, in the US it's usually around 70, occasionally defined as 65, generally outside of the US. Despite the fact that the average age for patients newly diagnosed with lung cancer is in the late 60s, trials done in lung cancer far disproportionately enroll younger patients.

As we established several years ago that it is indeed possible to do clinical trials with more than 50 or even 100 patients with advanced BAC, we were also seeing that those first forays into advanced BAC with standard chemotherapy were somewhat disappoingting (described further in another post).