After Avastin was found to produce a survival benefit when combined with chemo in advanced NSCLC, it became increasingly appealing to try to see if adding Avastin in earlier stages of lung cancer, both SCLC and NSCLC, where it might increase the cure rate.

In a talk at ASCO 2007, I was asked to present some commentary on a couple of phase II, single arm trials of patients with ED-SCLC that were reported by two different cancer cooperative groups in the US, each adding the anti-angiogenic agent Avastin (bevacizumab) to standard chemotherapy options in this setting.

At long last, and after years of planning, a new large phase III randomized clinical trial is getting underway to determine whether adding avastin to chemotherapy as post-operative (adjuvant) treatment for early stage NSCLC provides added benefit compared to chemotherapy alone.

As described in one of my first posts, Avastin was approved by the US FDA for the first line treatment of advanced NSCLC in patients with non-squamous cancers, no history of coughing up blood, and no brain metastases, based on the positive trial ECOG 4599 (abstract here) that demonstrated a survival benefit for carbo/taxol/a

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.

Last week, Genentech had a press release in which they disclosed some potentially important information about a large randomized trial being done in Europe with Avastin. This study, known as the AVAIL trial, enrolled just over a thousand first-line patients with advanced NSCLC to receive their most common standard chemotherapy, cisplatin and gemcitabine, alone or in combination with Avastin at either of two dose levels, 7.5 mg/m2 and 15 mg/m2. The basic design is as shown in this figure:

As mentioned in prior posts, the anti-angiogenic monoclonal antibody Avastin (bevacizumab) is now approved in first-line treatment of advanced NSCLC in combination with carboplatin/paclitaxel chemotherapy. Among the very interesting questions is whether Avastin should be added with other active drugs for NSCLC. Most of us in the field strongly suspect that the survival benefit from Avastin will also be the case with other types of therapy, but we’re only starting to get the evidence to address this.

Although Avastin has been approved for first-line treatment of advanced NSCLC, at this point it cannot be universally employed. Patients with squamous cancers account for something in the range of 30% of patients, while patients with brain metastases amount to about 10-15% of patients. Another 5-10% may have hemoptysis, or the symptom of coughing up blood, and many others are on therapeutic blood thinners for a history of blood clots or atrial fibrillation.

Avastin (bevacizumab), an antiangiogenic agent that works by blocking the blood vessel stimulating factor vascular endothelial growth factor (VEGF), has already been FDA approved and commercially available for colon cancer, but it has now been approved by the FDA for first-line treatment of non-squamous NSCLC in combination with standard chemo of carboplatin and paclitaxel (taxol).