Although much of our focus has been on targeted therapies, there are still new conventional chemotherapies that are being introduced and may have a meaningful impact on lung cancer. One that has been tested in late clinical trials, including a phase III randomized study, is vinflunine, which is a novel version of a chemo drug called a microtubule inhibitor, in the same general family as navelbine, one of our more commonly used drugs in NSCLC (and broadly useful in many cancer types). Leading side effects have most typically been decreased blood counts, fatigue, and GI problems like nausea/vomiting, abdominal pain, and constipation. Unlike taxol and taxotere, it doesn’t require any steroid premedication and is given by vein over just 10-20 minutes, typically one day every three weeks.
After the earliest studies, vinflunine was developed in lung cancer, including a second-line trial in 60 patients previously treated with platinum-based chemo (abstract here). There was an 8% response rate and another 50% with stable disease, so overall we can say that there’s proof of activity. But the big test was a randomized phase III trial conducted in Europe, randomizing 551 patients who had received first line chemo, to now receive either taxotere IV every three weeks or vinflunine IV every three weeks (abstract here):
The overall survival results were pretty much superimposable, as shown in the survival curves below:
They were remarkably similar overall, although the efficacy markers minimally favored taxotere. That really wouldn’t matter except that the side effect profile seemed, if anything, to disfavor vinflunine, with pretty comparable drops in blood counts but a little more in the way of fatigue, abdominal pain, and constipation.
Overall, vinflunine emerged as a reasonable alterative to taxotere in this setting, but there was no obvious reason to recommend it over the agents we have already. As I mentioned in describing oral topotecan for second line NSCLC (covered in prior post), taxotere is a fine choice that is already competing with alimta and tarceva as appealing alternatives in the second line setting that are widely perceived as being better tolerated. Another IV agent that is given every three weeks but is perhaps a little more challenging than the other alternatives is not likely to take the world by storm. It’s not clear whether the US FDA will be inclined to approve a drug as yet one more alternative with nothing to recommend it over the others. But if it becomes commercially available, it will still represent an addition to the rather short list of agents that has evidence of activity after prior chemotherapy, and it may be an appealing choice for patients who are fit enough to continue to pursue treatment through multiple lines over an increasingly longer (albeit slowly improving) period of time.
posted by Dr. West @ 10:44 pm link to this post
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December 21st, 2007 at 10:00 am
I think the real question for the FDA is whether or not there is cross-resistance with already approved chemos. As more patients need 3rd, 4th or 5th line treatment I think there is a real question whether something new would be better than going back to a chemo used 2 or 3 years ago. My wife has already used taxol,carbo and avastin in first line, taxotere with radiation in second line and now tarceva. All have worked well but at least until tarceva only for a few months. If needed alimta is her obvious next choice but if that doesn’t work it would be nice to have another alternative that works differently. What I think we need to know is if vinflunine would cause a response or stable disease in the same people or different people as currently approved agents. If diffferent people we need a way to identify them. On the subject of new agents HDAC inhibitors and HSP90 inhibitors look promising from what I’ve read and vorinostat(hdac inhibitor) is an approved drug for another indication so could be prescribed.
December 22nd, 2007 at 3:33 pm
agree that the key issue is what would actually be helpful in 3rd, 4th, and 5th line. The practical problem is that the pharmaceutical companies have a hard time enrolling patients on trials beyond second line, where a much lower proportion of patients get treated than 1st or 2nd line; also very importantly, if they ever get FDA approval, the market for their drugs is quite small. Practically speaking, this means it’s more time-consuming and expensive to develop a drug with a small market — a tough proposition.
It would be great if we weren’t so dependent on pharmaceutical companies having such a clear financial incentive to develop cancer treatments, but over the past 1-2 decades, US-based cancer research has been increasingly funded by pharma as federal funding for clinical cancer research has steadily declined. And political forces are channeling billions of dollars into Iraq and many other causes while the NIH has a hard time competing.
-Dr. West