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. In the US-based ECOG 4599 trial that compared chemo (carbo/taxol) alone to chemo/avastin and led to avastin's approval (abstract here), patients who developed a blood clot that required blood thinners were taken off of the study. But is that necessary?

The bit of evidence we have about FDAC and avastin comes from the AVAiL trial done in Europe that compared chemo (in this case, cisplatin/gemcitabine) and placebo to the same chemo with either low dose or high/standard dose avastin. While patients on the AVAiL trial were not eligible if they were already on FDAC before the trial, the study did allow patients who developed a blood clot while on treatment to stay on the trial after initiating blood thinners. This gave an opportunity to compare the rates of bleeding complications among the patients not on FDAC to those who started FDAC and continued with avastin.

Developing blood clots is pretty common among patients with cancer, especially those with adenocarcinomas, who were the clear majority of patients on this trial that also excluded patients with squamous cancers. A total of 86 patients, divided pretty evenly among placebo arm, low dose, and higher dose avastin, were followed on while on FDAC along with their treamtent. They were compared to 900 other patients who remained off FDAC. As presented by Natasha Leighl from Toronto (reference here), there were no serious or fatal pulmonary hemorrhage events (coughing up blood) in patients on FDAC while also on avastin; there was a higher risk of bleeding in all patients on FDAC, including those who received placebo instead of avastin, but the real excess of bleeding events were just the mild grade 1 episodes like slight blood streaking with a cough, or a bloody nose.

Other studies are beginning to look at blood thinners with avastin and other antiangiogenic drugs, and at this point it's really to early to declare it safe to give them together, but there also isn't a clear signal of a significantly increased risk of bleeding, at least not beyond the risk of bleeding we see in patients on blood thinners overall. I'll update with any new information if we see more study results presented at the ASCO meeting in early June.