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.

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?

Just last week I described in a prior post the news that a large trial of Nexavar (sorafenib) had been reported as negative in first line advanced NSCLC, and with some evidence of an increased risk of death on the novel agent in combination with chemo in the subset of patients with squamous cell NSCLC.

I'll get back to the storyline of our growing understanding of the differences of individuals based on pharmacogenomics very soon. But I wanted to give people some breaking news that just came out.

While the differences in anticipated clinical benefits from EGFR tyrosine kinase inhibitors like tarceva and iressa are well known (summarized in prior post), less well appreciated is the potentially significant differences in results with garden variety standard chemotherapy.

In the Q&A forums recently, members Jianming and Neil introduced us to the novel agent XL647, in clinical trials now, but I figured it was worth me collecting more background and providing a more thorough background. XL647 is an oral small molecular that inhibits multiple tyrosine kinases, receptors on cells that trigger cascades of activity in the cells, thereby leading to tumor development and growth.

The antibody to the epidermal growth factor receptor erbitux (cetuximab) (introductory post here) has been used as an effective treatment for colon and also head and neck cancer for several years, but its role in lung cancer has yet to be defined.

Although I've previously written about the question about optimal duration of therapy for first-line chemotherapy in advanced NSCLC (post here), these conclusions have been based on a limited number of trials. One study randomized patients to three or six cycles of rather old chemo and found no significant differences (abstract here).