The AVAiL trial in first-line advanced NSCLC, based in Europe, was designed to confirm the role of avastin with chemo using a different regimen of cisplatin and gemcitabine with a placebo or Avastin at 7.5 or 15 mg/mg every three weeks (the European trial was placebo-controlled, unlike the US-based Avastin trial with carbo/taxol). I described it in a prior post that described a glimpse of the results that were reported in a press release a few months ago, but we received more information at ASCO.

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.

Throughout their development over the past years, the EGFR tyrosine kinase inhibitors Iressa (gefitinib) and Tarceva (erlotinib) have been identified as seeming to be particularly helpful in women compared with men. Only Tarceva is commercially available in the US, but Iressa is widely used in other parts of the world, including Asia, where it continues to be avidly used and studied. Both of these drugs have a consistently higher response rate in women, which has led to some different use patterns in women and men.

While we are still working on figuring out the mechanisms underlying differences in the lung cancers of women vs. men, the efficacy and survival paint a consistent picture that women with lung cancer live longer than men regardless of the lung cancer subtype, stage, or treatment used (summary here). Large studies have reported that women have an approximately 15-20% improvement in survival, controlling for other variables, when compared to men.

Inhibitors of the epidermal growth factor receptor (EGFR), such as Iressa (gefitinib) and Tarceva (erlotinib) are generally known for being often minimally toxic, oral, targeted therapies that can occasionally produce dramatic and long-lasting responses in a minority of patients and more modest, minor responses or prolonged disease stabilization in a larger proportion of patients. They are not widely considered as a treatment for brain metastases, but there are many reports that describe responses, including prolonged ones, of brain metastases to Iressa or Tarceva.

One of the more common approaches to treating stage IIIA NSCLC with N2 lymph nodes (mediastinal, or mid-chest, on the same side as the primary tumor) is chemotherapy or chemoradiation before surgery. For those who recommend induction therapy (treatment before planned resection), there is a pretty even split between those who recommend chemotherapy alone and those who recommend chemo with concurrent radiation. So how do knowledgeable people come to different conclusions, and who is right?

Over the last several years, chemotherapy after surgery has become the standard strategy for improving survival compared to surgery alone, at least for stage II and IIIA patients who don't have mediastinal (N2) lymph nodes involved, and it's often used also for patients with stage IB NSCLC (no lymph nodes, but a larger tumor or tumor involvement with the pleural lining around the lung). However, another approach that has been studied, albeit less so than adjuvant (post-operative) chemotherapy is neoadjuvant (pre-operative, also known as induction) chemotherapy.

Small cell lung cancer (SCLC) has been a very challenging disease for patients and physicians, and unfortunately one in which our improvements in treatment have been few and far between. In fact, a recent educational session at ASCO was titled "Small Cell Lung Cancer: What's New Since 1978?". The decreasing frequency of SCLC has also made it increasingly difficult to study, but even when the studies are completed, many emerging potential therapies have proven to have no benefit.

I briefly mentioned the potential value of surgery for a solitary brain metastasis, where it is commonly used, in another post. Today I'll talk more specifically about where the role for surgery has been specifically tested for brain metastases in lung cancer.

A novel agent called motexafin gadolinium (MGd), with a marketed name of Xcytrin, has been studied as a potential neuroprotectant as well as radiosensitizer that may allow patients with brain metastases to do better when it as added to whole brain radiation therapy (WBRT) than they would with WBRT alone.