I’ll need to go into more detail on many of these subjects in the next few weeks, but here are a few very brief highlights of what we’ve seen:
The Japanese study V-15-32 in which Iressa was compared with Taxotere as second-line therapy in Japanese advanced NSCLC patients was presented in far more detail that the small glimpse that was previously publically available. As I described in my post describing the preliminary analysis of these data, Iressa was associated with a higher response rate but a lower survival at a year and overall emerged as disappointing, especially since Iressa has generally performed best in Asia. However, considerably more patients on the Taxotere arm got treatment after progressing (most getting Iressa) than patients on the Iressa arm, so the survival difference may be confounded by patients assigned first to Taxotere being likely to get more therapy overall.
A new chemo drug called vinflunine was compared to taxotere as a second-line treatment for advanced NSCLC and showed no real difference in activity, but it did seem to cause more abdominal pain and constipation, so it’s not clear that there’s any reason to recommend it over the options we already have.
A trial that gave four cycles of first-line chemo for advanced NSCLC (carboplatin/gemcitabine) followed by immediate taxotere or holding of taxotere until patients showed progression actually showed a strong hint of a survival benefit for immediate taxotere rather than waiting. However, an unusually large proportion of patients on arm to receive the delayed restart of chemo never ended up getting that treatment, for one reason or another (often rather rapid progression). While provocative it’s not clear that this should change standard practice, especially since other studies asking similar questions have not clearly supported this conclusion.
The biggest news of the first day of ASCO in the lung cancer side was unfortunately a negative trial. The Hoosier Oncology Group ran a trial in which patients with stage III, unresectable NSCLC were randomized to chemo (cisplatin and etoposide) with radiation starting at the same time, for two cycles of chemo and about 7 weeks of chemo, all followed by either observation alone after that or three more cycles of chemo with taxotere (”consolidation taxotere”). While consolidation chemo has become pretty much a standard, with about 2/3 of oncologists now using this approach, its role had not been proven, and this trial showed no benefit for the added treatment. It appears based on this new regimen that the standard practice may shift significantly, with the value of the taxotere after combined chemoradiation now challenged by a trial that shows no improvement in outcomes, although all of the patients did respectably well overall.
This same concept of chemo and radiation together, followed by taxotere, and then randomization to placebo or Iressa as maintenance therapy was presented with longer follow-up. I described this trial in a prior post, but the news now is that with longer follow-up, the detrimental effect of Iressa in this setting became even clearer and actually is now statistically significantly worse than placebo.
That’s just a few highlights. I’ll add more tomorow.
posted by Dr. West @ 9:08 pm link to this post
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June 4th, 2007 at 8:45 am
Any news on vitamin D and NSCLC? Vitamin D is all over the news today as possibly having positive effects on some cancers.
June 4th, 2007 at 11:50 am
You reported vinflunine showed no difference in activity to taxotere. Does vinflunine fight the cancer differently so that it could be used a another weapon in the arsenal?
June 4th, 2007 at 8:07 pm
Sally,
I presented a poster on a vitamin D receptor agonist in lung cancer (in combination with taxotere), but I don’t think it made the national news. I’ll be happy to report on that topic at some point, but whatever you’re referring to didn’t make a ripple of interest in the lung community. I have been buried in a lung-specific world and haven’t heard much about whatever buzz is being generated from other fields.
Welthy,
Vinflunine is in the same general class as drugs like navelbine, so I don’t think it will be a straightforward drug approval by the US FDA. We already have three drugs approved by the FDA for second line therapy (taxotere, alimta, tarceva), so it would likely need to show benefit in some other setting to be viewed more favorable, I suspect.
-Dr. West
June 4th, 2007 at 9:18 pm
The Vitamin D story that I saw today was not a result of the ASCO conference. It was a more general Newsweek (I think) piece. The only three ASCO stories that I’ve seen in the mainstream media have been:
1. Story on supplements (shark cartilage not so good, ginseng good for side effects of treatment, and flaxseed may inhibit prostate cancer);
2. Lower doses of radiation are just as effective in breast cancer treatment;
3. Sorafenib provides a significant survival benefit in liver cancer (the one sorafenib abstract that I saw with respect to NSCLC had less dramatic results).
Sorry, Dr. West, no sign of your paper yet!
June 5th, 2007 at 10:26 am
Any news from the ASCO about Tarceva and PPI’s?
June 5th, 2007 at 2:10 pm
I had a sneaking suspicion my presentation hadn’t made national news.
As for Tarceva and PPIs, I had the opportunity to discuss this with several people from OSI Pharmaceuticals and Genentech, most of whom were relatively unaware of this even being an issue, so they didn’t have any answers. I emphasized how important this topic is to people on tarceva, and how important it could be to improving results with tarceva, but for now I don’t have any more answers. But at least more people understand the question.
-Dr. West
June 6th, 2007 at 12:02 pm
Dr. West: I read the abstract of your poster. It certainly looks important, but DEFINITELY not sexy!
My (very interested) layperson’s view from afar was that:
1. There were no huge breakthroughs in lung cancer treatment (which kind of makes sense, since if there had been one, it’s not clear that folks would have waited for the conference to reveal it), but lots of incremental improvements.
2. Alimta and Avastin were two of the big stars of the conference in lung cancer, to the extent that there were “stars”.
3. Axitinib might be the “next great” targeted therapy (down the road).
How accurate is my read of things?
June 6th, 2007 at 9:27 pm
I wouldn’t saw it’s electrifying at this point. It’s interesting enough, showing a hint that it may add some increase in activity or at least a decrease in side effects vs. standard taxotere, but that can’t be clarified without a larger trial. And it’s not clear that the company will be proceeding with any large lung cancer trials. Their focusing on prostate cancer primarily right now.
I would say that there were two practice changing findings from ASCO. One is that prophylactic cranial irradiation was associated with a survival benefit for patients with ED-SCLC who had any kind of objective response to chemo, so this will likely lead to more use of PCI. The second was that consolidation taxotere after concurrent chemoradiation in stage III NSCLC, which has been routinely administered based on good suggestive evidence of it being beneficial, actually showed no benefit in a head to head comparison vs. observation (no further chemo or other treatment) after the concurrent chemoradiation.
I think there were only some modestly provocative findings overall in lung cancer, and I don’t think anything reached “star” quality.
And I think axitinib is among the agents that showed real promise, but the work is too early for me to characterize it as “next great therapy”. I would say that nothing earned that title this year, but a vaccine against something called MAGE looked pretty promising, and it’s being studied in a larger study in the post-op setting that is just getting started. More later.
-Dr. West