I’m about to get on my flight back home, but I wanted to just give people a glimpse of the four presentations that were included in the Presidential Session of the meeting this morning.
The first was by Dr. Gary Strauss from Tufts Univ. in Boston. He presented evidence on the changing demographics of lung cancer, specifically the evidence that over the past several decades, the shift to increasing adenocarcinomas, often peripheral in the lung, correlates with the shift to low tar, filtered cigarettes that were associated with people taking deeper breaths and having the particulates go out further in the lungs than in a time before filtered cigarettes.
The second presentation was by Jean-Yves Douillard from Villejuif, France, who presented a worldwide trial that randomized patients who had received 1-2 prior lines of chemo to either Iressa or Taxotere. This trial showed that Iressa provided equivalent survival and a little better toxicity profile. Surprisingly, it didn’t show that the patients who had EGFR gene amplification as measured by FISH testing did any better with Iressa than Taxotere. There really weren’t any subgroups that did notably better with Iressa, including never-smokers and Asian patients (both about 20% of the patients on the trial), which was also a little surprising. Nevertheless, it’s a study that shows that EGFR inhibitor therapy can offer equivalent survival and in several parameters more favorable tolerability. Iressa may scrabble its way back toward (re-)approval by the FDA, but it’s not clear what this means in a world where Tarceva is also available and has shown a survival benefit compared to placebo but Iressa did not.
The third trial was by Dr. Giorgio Scagliotti from Turin, Italy, who presented a randomized trial of cisplatin/alimta vs. cisplatin/ gemcitabine in previously untreated patients with advanced NSCLC. He demonstrated that the overall survival was identical between the two regimens but that cisplatin/alimta had fewer side effects in multiple categories, most notably decreased blood counts and need for transfusions and drugs like neupogen. While the finding that two chemo doublets are equivalent in survival isn’t fascinating, what was very interesting was his report that patients with adenocarcinomas or large cell carcinomas did significantly better with cisplatin/alimta, while patients with squamous cell cancers did significantly better with cisplatin/gemcitabine.
Dr. S.M. Lee from London presented a trial on small cell lung cancer, testing whether thalidomide added to cisplatin and etoposide for SCLC improved survival. Thalidomide is an oral drug that has anti-angiogenic activity, and it’s been proven to be useful for patients with multiple myeloma, a cancer of the plasma cells in the blood. Unfortunately, not only did it not provide a benefit, but patients who received it did worse than the patients who received a placebo instead, and thalidomide is also associated with some side effects like increased risk of blood clots. Moreover, in the hour after that presentation, Dr. Lee presented another randomized phase III trial of chemo with thalidomide or placebo for first-line NSCLC, and it was unfavorable in that setting as well.
More later. I’m a-leavin’ on a jet plane.
posted by Dr. West @ 12:56 am link to this post
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September 5th, 2007 at 7:13 am
Gosh, any good news to report?
Have a safe trip home Dr. West, and thanks for the quick update.
Jim
September 5th, 2007 at 9:41 am
Dr. West: I hope you had a good trip back and can figure out your time zones soon!
Thanks for all of this interesting information. From a self-interested point of view (even though it’s not a perfect fit), I’m curious about the Scagliotti study, especially the subgroup findings. A few questions if you get a moment:
1. I know you were typing quickly before departure, so I want to double-check: was there really a statistically signficant difference based on histology?
2. How big was the difference?
3. Was the histology subgroup analysis part of the study originally, or was it just an “interesting” post-hoc finding? If the latter (and I suspect that’s the case given the somewhat unusual grouping of adenocarcinoma and large cell–that just screams “post-hoc”), I guess I’m less impressed. I could think off the top of my head of about 9 distinctly different subgroup analyses that could be run with this study (based on sex, age, race, histology, stage, smoking status, etc.), and it wouldn’t be terribly surprising that random variation produced a “significant” result in one of those (if you’re willing to accept a 5% chance of being wrong a whole bunch of times, it is quite possible that this will happen once).
4. Tied in with that, is there any theoretical basis for expecting Alimta or Gemzar to be more effective in one histology than another?
5. Or, are there any previous findings that are consistent with this?
Sorry for all the questions; I guess I’m overwhelmed by skepticism today.–Neil
September 5th, 2007 at 9:27 pm
I’ll provide a few more details in a post later. I’m still trying to get back into the swing of things. I don’t have the figures yet, but I have a lot of the stats and more impressions to share on Dr. Scagliotti’s presentation of cisplatin/alimta vs. cisplatin/gemcitabine.
-Dr. West
September 6th, 2007 at 3:31 am
Fantastic! I was rather stunned that you were doing anything on this site yesterday (I mean the yesterday that you had in Seattle, not the one that you had before that in Seoul). Get some sleep!–Neil
September 8th, 2007 at 1:38 pm
I just got answers to most of my questions above from the following source:
http://www.medpagetoday.com/Pulmonary/IASLC/tb/6585
Answers, as I understand them are:
1. Yes, it’s statistically significant.
2. The difference was 1 to 2 months in median survival (pretty big, as these things go).
3. The histological subgroup analysis was not post-hoc as I had suspected. It was a pre-planned part of the study.
4. There is a theoretical reason for expecting such differences.
5. I still believe it is the first such finding.
Sometimes, even skeptics can be largely convinced. Am I going too far the other way now?–Neil
September 9th, 2007 at 7:13 pm
Yes, that’s right. I’m hoping to get the slides and additional other details in the near future, but if I don’t get them soon, I’ll just write a post in the next few days anyway and provide info based on my own notes along what I can find on pages like the one you provided.
I can tell you that having viewed the curves myself after several years of reviewing survival curves in oncology, these appeared clinically as well as statistically significant. You didn’t need the statistical analysis to appreciate the differences between the curves, so I’d call the findings pretty convincing. But yes, they were also among the earliest evaluations of this kind of work. I did learn that a subsequent analysis of the Hanna trial that compared alimta to taxotere (Journal of Clinical Oncology, 2004) also revealed in a post-hoc analysis that pemetrexed recipients with adenocarcinoma histology also did better than recipients of taxotere. Suffice it to say that studies of different results by histology haven’t been reported much up until now, but not many trials have looked hard for this either. I suspect that just as we started conducting more detailed analyses of smoking status with EGFR inhibitors, now after this trial with cisplatin/alimta we will see much more detailed analyses of results of chemotherapy by particular NSCLC histology.
-Dr. West
September 9th, 2007 at 7:20 pm
And two different post-hoc analyses with the same findings are MUCH more convincing than one. From a personal practical standpoint, that makes me feel much better about still having Alimta on the bench awaiting me! I look forward to reading your post!–Neil