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Podcast of Q&A Portion from Molecular Markers Webinar with Dr. Pennell
Here’s the podcast of the Q&A portion of the excellent webinar with Dr. Pennell on Molecular Markers in Management of NSCLC.
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Podcast: Play in new window | Download (37.8MB) | Embed
Dr. Alan Sandler Provides General Intro to Treatment of Advanced Non-Small Cell Lung Cancer
Dr. Alan Sandler is an international leader in the lung cancer world, also identified as among the most down to earth and funniest people in the field (and though that might not sound like much, he travels with an audio clip of a rim shot to play after his jokes). His talks are light-hearted, but he’s so highly regarded because he has also been deeply involved in several of the pivotal research activities that have helped shape our current treatments. He led the original study that led to the approval of gemcitabine in lung cancer, and more recently he led the ECOG 4599 trial that was published in the New England Journal of Medicine and established the benefit of Avastin with carbo/taxol for advanced lung cancer.
Dr. Sandler recently moved from Vanderbilt to my corner of the world (more or less), where he leads the Division of Hematology and Oncology at Oregon Health & Science University in Portland. He was kind enough to participate in our NSCLC Patient Education Forum, where he provided a general introduction to the biggest questions of managing advanced NSCLC: does treatment really help, and how much? He also provided an overall review of the landscape in how we approach first line therapy for metastatic NSCLC, from someone who has been a big part of developing those standards.
Here is the audio and video versions of his presentation, along with the accompanying figures and transcript.
sandler intro to first line treatment of advanced nsclc audio podcast
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sandler-first-line-treatment-of-advanced-nsclc-transcript
I’m trying to leverage my proximity to Dr. Sandler, as well as my longtime friendship with him, to get him to involved with more of our GRACE activities. Fortunately, he’s been very gracious and generous with his time, so get more of his perspective , and maybe even some good jokes, from him in the future as well.
Podcast: Play in new window | Download (36.2MB) | Embed
Dr. Gerard Silvestri, Pulmonologist, on Lung Cancer Workup and Staging
This is the first of the presentations by guest speakers at our NSCLC Patient Education Forum back in September. Dr. Gerard Silvestri is a pulmonologist, a lung disease specialist (not only cancer), and he is also one of the most important leaders in lung cancer within the field of pulmonology, as both a writer of some very important work and as a great speaker.
His talk was a general introduction to the process of the workup and approach to staging a lung cancer. Below you’ll find the links to audio and video versions of his presentation, the figures, and the transcript for his talk.
Silvestri Lung Cancer Workup and Staging Audio
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silvestri-lung-cancer-workup-and-staging-transcript
Podcast: Play in new window | Download (49.5MB) | Embed
BAC No More?
The most expert lung cancer pathologists in the world are planning a revision of the classification of lung adenocarcinomas that is expected to be approved and implemented next year, and it’s going to make some big changes. Specifically, it’s planning to eliminate the diagnosis of bronchioloalveolar carcinoma (BAC), reflecting our evolving understanding of this disease.
BAC with lesions less than 2 cm is now being designated as a pre-cancerous adenocarcinoma in situ (AIS), which essentially means it’s a pre-invasive condition with a favorable prognosis. In fact, the available literature, largely from Japan but also including evidence from other parts of the world, shows a 100% 5-year survival for a <2 cm AIS, which is far more commonly the non-mucinous BAC sybtype. The size limit is significant, however, because larger lesions are felt far more likely to have at least some area of invasive disease.
The invasive portion of what is now in the spectrum of BAC with focal invasion to adenocarcinoma with BAC features has a major impact on prognosis. In fact, the size of that invasive component is what drives prognosis, not the invasive part:
The Invasive Component in AdenoBAC Drives Prognosis
So a largely pre-invasive (adenocarcinoma in situ) lesion with a small area of invasiveness will now be designated as minimally invasive adenocarcinoma, and it also has a 100% cancer-specific survival at 5 years.
Clinical Factors on the FLEX Trial: Do Certain Patient Groups Benefit More or Less with Erbitux?
In the last post that presented the highlights of the FLEX trial that tested the benefit of adding Ebritux (cetuximab) to standard chemo. The trial was technically positive, statistically significant, but the results in the overall population of the trial were so marginally superior with Erbitux that a very logical follow-up question is whether we might identify certain subgroups of patients who benefit more, enough to definitely add Erbitux, while not pursuing it for other subgroups that appear to benefit much less.
It’s important to add a word of caution about interpreting information gleaned from patient subsets. Clinical trials are generally designed to have enough patients to show differences in the entire trial with everyone. Nevertheless, when you dissect it ten different ways, the smaller subgroups don’t have adequate numbers to show significant differences, even when they may really exist. At the same time, doing multiple different comparisons escalates the chance that you’ll randomly find differences that aren’t real, and that occur just as a product of random chance. In fact, trials are generally powered to consider a difference as significant only if the probability of the difference happening by chance is less than 5%, but if you slice and dice the results to do ten different subgroup tests, the likelihood of at least one coming up positive just by chance is now 22%.
So these comparisons aren’t really conclusive and are better suited for shaping our ideas for future research than for guiding our treatment decisions. In reality, people (present company included) tend to pick and choose which subgroups they focus on to support their inclinations, while discarding other comparisons.
To provide the general picture, there’s a figure called a forest plot that shows the performance of multiple subgroups simutaneously. Here, the size of the different subgroups is represented by the size of the black ovals, and the position of the oval to the relative to the vertical line shows whether the Ebritux group did better (if the oval is to the left of the vertical line, sometimes referred to as “unity”) or the chemo alone arm did better (if the oval falls to the right).
FLEX Trial Forest Plot
(Click on image to enlarge)
Interview with Dr. Suresh Ramalingam on First Line and Maintenance Therapy for Advanced NSCLC
The ASCO meeting I’m at right now is so busy that there really isn’t time to write a new post (though I’m still “tweeting from the meeting”). Though the talk show hows just air re-runs of old shows when they’re on vacation, I’m trying to continue to add new content to the website during this time (and it’s about as far from a vacation as anyone has in Orlando).
Here’s an interview I did with Dr. Suresh Ramalingam, medical oncologist and Director of the Thoracic Oncology Program at Winship Cancer Institute at Emory University. It covers the current status of initial treatment for advanced NSCLC, including controversies and shifting standards for first line and then the transition into maintenance therapy. There’s also an associated slide set (as a pdf file), a transcript, and a link to the audio (mp3) version.
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Ramalingam First Line and Maintenance Rx for Adv NSCLC Audio Podcast
Podcast: Play in new window | Download (0.4KB) | Embed
Interview with Dr. Ramalingam on First Line Advanced NSCLC and Maintenance Therapy
The ASCO meeting I’m at right now is so insanely busy during the days and nights that it’s next to impossible to carve out the time to write posts during the meeting. While the talk show hosts just show re-runs while they’re on vacation, we’re at least going to put up some new content, even if it’s from work previously done (and this is far from a vacation).
This podcast features Dr. Suresh Ramalingam, Director of the Thoracic Oncology Program from Winship Cancer Institute at Emory University in Atlanta. We discussed recent data that have led to changes in our current treatment standards for first line treatment of advanced NSCLC, as well as emerging evidence leading to debates about maintenance therapy after a fixed amount of initial chemotherapy. The video version includes synchronized figures. The audio is an mp3 file.
Ramalingam interview Adv NSCLC and Maintenance Aud
I’ll add the figures and transcript very soon.
Podcast: Play in new window | Download (62.3MB) | Embed
Video Presentation on Timing of Chemo after First Line for Advanced NSCLC
With special thanks to Harvey and Bernice Janssen for providing support to make it possible, I’m pleased to post a new video presentation on the topic of Timing the Transition to Maintenance/Second Line Chemotherapy for Advanced NSCLC. We can expect new information to emerge in the coming months and years, but here is the current snapshot of what we know, along with a little describing what I think (noted as such), about this important topic today.
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Lung Cancer and the Enzyme Connection
Erlotinib (Tarceva) was approved for treatment of progressive non-small cell lung cancer (NSCLC) after the BR21 study that showed that tarceva not only improved survival but also improved lung cancer symptoms and quality of life. This study and others have also taught us that the benefit of tarceva is much better in those who had never smoked and less effective in current smokers. It is important to note, however, that even those who currently smoke obtain a benefit from treatment with tarceva, albeit smaller.
In the wake of the BR.21 trial, it became known that certain EGFR mutations in the tumor are associated with a dramatic benefit with tarceva, as well as the other EGFR tyrosine kinase inhibitor (TKI) gefitinib (Iressa).We also began to realize that these EGFR mutations were found most commonly in never smokers and rarely in current smokers.
There it was: the reason why tarceva worked better in never smokers. But in fact that was not the whole story. Tarceva, like many other drugs, is broken down in the body by an enzyme group called CYP 1A1/1A2. Enzymes are proteins that help to break down and digest our food, but enzymes can break down and digest many other things as well. The products in inhaled tobacco smoke stimulate this enzyme CYP, which then further breaks down tarceva in the body before it has a chance to work.
VeriStrat Test for EGFR Test: Initial Impressions after Sending a Few
A few weeks ago I described a blood test for predicting survival after getting an oral epidermal growth factor receptor (EGFR) inhibitor that is just becoming commercially available. This is called the Veristrat test and from company called Biodesix. As I noted previously, this technique looks at the protein patterns in a patient’s serum and reportedly can reliably predict whether a patient is likely to have a prolonged survival after receiving an EGFR inhibitor. The company gave me the opportunity to send off a few of these tests at no charge, and after a few weeks of trying it in a handful of patients, I’m finding that it seems to do what it says it does, for better or for worse.
What they specifically say is that, by separating serum samples into the two thirds that will have a “good” survival and the one third that will have a “poor” survival after getting an EGFR inhibitor, clinicians can use this test to determine which patients shouldn’t get an oral EGFR inhibitor like tarceva (erlotinib) or iressa (gefitinib) for advanced NSCLC. The test may well be great for this, but I haven’t had the opportunity to send this test off in the last few weeks for this purpose.
Instead, what I was hoping we might use this test for is to get a faster answer about whether a patient will do well with an EGFR inhibitor. Even though I and many other lung cancer experts are increasingly becoming converts to the idea that EGFR mutations are quite relevant and override clinical predictors of benefit with EGFR tyrosine kinase inhibitors (TKIs), these mutations aren’t always very accessible. Only a minority have enough tumor tissue from their original biopsy to send off for mutation testing, and the test itself takes 3-4 weeks, which is long enough that many patients will not be inclined to sit around and wait for a month before starting treatment.
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