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”).

One of the novel agents being studied in lung cancer is sutent (sunitinib), a multi-targeted oral anti-angiogenic drug that I’ve described in a prior post.

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.

One very important trial that has changed how we treat previously treated patients with advanced NSCLC has been a trial coded JMEI by Lilly, which sponsored this phase III randomized trial that directly compared second line treatment with alimta (pemetrexed) against the only FDA-approved second line treatment at that time, taxotere (docetaxel).

Several members have asked about the appropriate dose of avastin (bevacizumab), which is really still a controversial subject. It's worth exploring how we got here and where we are now.

While other doses of avastin have been used with other tumor types, the first study in lung cancer that used avastin tested two different doses, 7.5 mg/kg or 15 mg/kg combined with carboplatin and taxol (paclitaxel). This work was done at Vanderbilt Univ. Cancer Center by Dr. David Johnson and colleagues, and Dr. Laskin worked with them for a couple of years. This study had the following design:

One of the issues we struggle the most with, as oncologists, patients, and families, is how to choose a therapy that won’t make someone feel worse. There are so many things to factor into these decisions: what is the baseline function of the person, what comorbidities (other chronic illnesses) might interact or interfere, what side effects are acceptable or worth the risk, to what degree is the cancer interfering with their functioning and can this be reversed with chemo, and of course what does any individual patient want and expect from chemo?