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.

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.

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:

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.

Several trials have recently opened up for never-smokers with any lung adenocarcinoma or those with BAC (or adeno/BAC mix, invasive adenocarcinoma with BAC features) with any smoking status. Both of these groups have only recently gained recognition as likely being a distinct clinical entity with a different natural history (clinical behavior outside of treatment) and pattern of responsiveness to treatments that is different from other types of lung cancer.

In my recent post on the JMDB trial that randomized patients between cisplatin/alimta and cisplatin gemcitabine in first line treatment of advanced NSCLC, the take home conclusions were that overall efficacy was very similar, with the cis/alimta arm looking a little better in several side effect parameters, most notably a less significant decline in blood counts and lower risk for fevers with a low white blood cell count.

I've recently received some questions about the advantages and disadvantages of maintenance Avastin as a single agent for patients after completion of 6 cycles of first line chemo and avastin together for avastin-eligible patients. While this is generally considered to be a standard of care, many oncologists question whether it should be done. It's worth looking at how that standard came about and the strength of the evidence for it.

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.