When I first described the developing work with the EGFR monoclonal antibody erbitux (cetuximab) two years ago (see prior post), I described a trial that was just getting started called SWOG 0536.

As a general rule, companies don't sit on great news with their drugs. Without any insider knowledge, this was my concern about why we hadn't heard anything about the results of three major lung cancer trials with the agent Zactima (vandetanib), which I had written a post about 8 months ago (see prior post about these trials with Zactima, an oral agent that inhibits both VEGF, a major mediator of angiogenesis, and the EGFR pathway).

One of the central ideas in medical oncology is that if you have two or more anticancer treatments that are active, you test them together to determine whether it's safe and whether the combination works better than each individually. We've been doing this with chemotherapy combinations for decades, but it's only been in the last few years that we have had more than one targeted therapy in lung cancer with enough activity to move ahead with combination work.

With last week's FDA approval of alimta in the first line setting for NSCLC, we're likely to see a lot of alimta (pemetrexed) use shift from the second and third line setting to first line. Alimta's been a very popular choice for previously treated patients, based on issues like the relatively convenient schedule of a ten minute infusion one day every three weeks, no hair loss, and typically less of a drop in blood counts than seen with some other regimens.

Last week, updated information on the AVAiL (AVAstin in Lung cancer) trial (see prior post) of cisplatin/gemcitabine with either placebo or a low or higher (full) dose of avastin was presented in a meeting in Stockholm.

The European Society for Medical Oncology (ESMO) Congress, similar to ASCO but based in Europe, has been going on in Stockholm, where the results of a study called the First Line Iressa versus Carboplatin/Paclitaxel in Asia Study (taking some liberties to force it into the acronym "IPASS") was presented in the Presidential Symposium by my friend and Hong Kong-based colleague Tony Mok.

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.

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.

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):