Last week, the preliminary results of interim analysis the ESCAPE (Evaluation of Sorafenib, Carboplatin, And Paclitaxel Efficacy in NSCLC) trial were presented by Dr. Scagliotti at the 1st IASLC (International Association for the Study of Lung Cancer)-ESMO (Eurpean Society for Medical Oncology) Lung Cancer Conference in Geneva, Switzerland. This was a randomized, placebo-controlled, double-blind phase III study for patients who have not yet had chemotherapy for advanced NSCLC.

Continuing with the analysis of a publication about tarceva (erlotinib) for patients with advanced BAC that I introduced in the last post, we'll turn now to the analysis that Dr. Vince Miller and colleagues did on the biomarkers that might predict more or less clinical benefit with an EGFR inhibitor like tarceva (abstract here).

Tumor cavitation has been one of the issues we really haven't discussed but that has been a challenging question as we test more and more anti-angiogenic drugs, which target the tumor blood supply, in the setting of lung cancer. Since we started testing these agents, we've noticed that in addition to sometimes increasing the rate of tumor shrinkage, many patients who receive anti-angiogenic drugs develop cavitation, or a response on the inside of the tumor that leaves the rim of the tumor intact, as shown here:

Because the anti-angiogenic drug avastin (bevacizumab) has been associated with some degree of increased risk of bleeding since the beginning of its development in lung cancer, the key trials have historically excluded patients who have been on blood thinners, at least at the standard dose (full dose anti-coagulation, or FDAC). In fact, though, patients with colon cancer have historically not been restricted, so the question has really been whether it's necessary to restrict NSCLC patients who need FDAC from receiving avastin.

Although it’s only a leak from a “reliable source”, news came yesterday (link here) about a new lung cancer development from a financial source (yet another example of us learning oncology from Wall Streeters). Specifically, we heard that the BMS-099 that I described in a prior post is actually demonstrating a significant benefit in overall survival (OS).

We got some big news in the form of a press release today: avastin (bevacizumab) didn't produce a survival benefit in the European AVAiL (AVAstin in Lung Cancer) trial of cisplatin/gemcitabine with or without avastin at either a higher dose (15 mg/kg IV every three weeks) or a lower dose (7.5 mg/kg IV every three weeks):

Since the anti-angiogenic agent avastin (bevacizumab) has been shown to confer a survival benefit in a subset of patients with previously untreated advanced NSCLC (see prior post), we have been struggling with questions of whether the restricted eligibility requirements in the pivotal initial avastin trial were necessary.

I’ve previously described the concept of the “precocious metastasis”, the situation in which a patient presents with early stage NSCLC, except for a single metastasis, most typically in the brain or adrenal gland. Our conventional teaching is that a patient with any metastatic disease almost certainly has additional micrometastatic disease, cancer cells floating in the bloodstream, that will inevitably lead to development of new areas of visible metastatic disease in the future (so having a small amount of metastatic disease would be like being “a little pregnant”).

The epidermal growth factor receptor (EGFR) is a central component of a cell pathway for growth and cell division that is thought to be affected in many cancers, including NSCLC. EGFR inhibitors have been the focus of clinical trials for several years and are now used for many types of cancer.

Completing the analysis of the randomized trial that compared alimta (pemetrexed) and taxotere (docetaxel) in second line treatment of NSCLC (abstract here), which showed nearly identical response rates and survival but a more favorable side effect profile with alimta, another retrospective review of results looked at differences between the arms in older vs.