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. The presentation noted that both groups receiving avastin had a significantly longer progression-free survival than the folks who received a placebo. The trial wasn’t designed to compare the two doses, but it’s hard not to, because we need to choose just one of them. The hazard ratio (describing the total improvement over time) was more favorable at the lower dose, and I’d say that the curves showed more separation at the 7.5 mg/kg dose. Importantly, there were no clear differences in safety issues between the lower and higher dose, so side effects weren’t obviously dose-dependent. We didn’t see any survival data, which was considered to early to present, but we should see that in the next year, I’d suspect. In the meantime, it appears that there’s a lot of reason to debate whether we should be using the lower dose of avastin that appears to offer the same benefit as a higher dose, or whether we should continue to use the 15 mg/kg dose that has the proven survival benefit with carbo/taxol and that is approved by the FDA.

A couple of other trials also combined avastin with standard chemo options for first-line treatment of ED-SCLC, and we saw that this is generally safe and feasible, with no episodes of pulmonary hemorrhage (coughing up blood), and the results from each of these trials were modestly encouraging, but didn’t hit the ball out of the part. Some of the cancer cooperative research groups are considering moving forward with a larger trial of chemo with or without avastin in the first-line treatment of ED-SCLC.

Another trial in ED-SCLC, out of Europe, compared carboplatin and irinotecan to carboplatin and etoposide, noting a modestly better survival for patients who received carboplatin and irinotecan. Of note, the results with carboplatin and etoposide were a little on the low side, but carboplatin/irinotecan certainly looked like a fine option, and it’s a regimen that I have also used in a clinical trial in SCLC and found that patients generally tolerated quite well and had done similarly to other common regimens. Importantly, most of the more encouraging results we’ve seen with irinotecan in SCLC have come out of Japan, where the drug was developed, and it just so happens that the Asian population has genetic features that are associated with a better ability to tolerate irinotecan compared to those of European or African descent. So seeing a trial in which irinotecan does well outside of Asia is particularly notable, as we are recognizing that there are good reasons to repeat trials with different populations to check if the best treatments in Asia are truly the best treatment in North America or Europe or elsewhere.

The most interesting work on the ED-SCLC front was the finding from a European cancer cooperative group, the EORTC, that prophylactic cranial irradiation (PCI) significantly improved survival for patients who had either a complete or even just a partial response to first-line chemo.

I’ll add more highlights soon.