GRACE :: Lung Cancer

Podcast of Q&A Portion from Molecular Markers Webinar with Dr. Pennell

Dr West — Sun, 07 Mar 2010 19:52:10 +0000

Here’s the podcast of the Q&A portion of the excellent webinar with Dr. Pennell on Molecular Markers in Management of NSCLC.

dr-pennell-molecular-markers-qa-audio-podcast

dr-pennell-molecular-markers-qa-transcript

dr-pennell-molecular-markers-qa-figures

Obviously, people may have additional questions about this topic but who weren’t able to attend the live program. If you’d like to ask a question about molecular markers in lung cancer after this point, Dr. Pennell and/or one of the other GRACE faculty will be happy to try to give our best answer.

By the way, thanks again to Response Genetics for their grant to support this educational program.

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Round Table with Drs. Anne Tsao and Alex Farivar, Part 2: Mesothelioma

Dr West — Fri, 05 Mar 2010 04:19:21 +0000

This is part 2 of my round table case discussion with Dr. Anne Tsao, a medical oncologist and thoracic oncology expert from MD Anderson Cancer Center in Houston, and Dr. Alex Farivar, a thoracic surgeon with expert training in mesothelioma at Swedish Cancer Institute in Seattle. This particular case covers a patient with a mesothelioma, cancer of the lining around the lung, which is also known as malignant pleural mesothelioma.

Here is the audio and video versions of the podcast, along with the transcript and figures.

round-table-with-drs-tsao-and-farivar-part-2-meso-case-audio-podcast

round-table-with-drs-tsao-and-farivar-part-2-meso-case-transcript

round-table-with-drs-tsao-and-farivar-part-2-meso-case-figures

By the way, my apologies for the poor audio quality, a combination of inadequate recording, passing buses outside of the public space we were in, etc. It’s audible and still useful to people who are interested in learning about this topic, but this recording is below the standard for which we’re striving. To be honest, part of the audio quality issue was that we went for a lower cost sound guy, and it shows. So please consider a contribution, because it goes for things like having our podcasts sound better. You get what you pay for, and we would prefer to do better than “shoestring budget” quality.

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Watching Small Lung Lesions Do Nothing: “Ground Glass Opacities” Don’t Progress Over Years If They’re Watched, Not Resected

Dr West — Wed, 03 Mar 2010 03:36:45 +0000

In one of my earliest posts about bronchioloalveolar carcinoma (BAC) (in the dark ages, pre-Twitter), I wrote on the subject of managing small BAC-type lesions, which tend to appear as small hazy areas called “ground glass opacities” (GGOs) and suggested that some of these cancers may be so indolent that they don’t need to be treated, even if they have the word “carcinoma” in the diagnosis.

(a representative GGO identified by arrow)

Now there is a proposal to change BAC to “adenocarcinoma in situ“, a pre-cancerous condition, reflecting the idea that these lesions have such a favorable prognosis that they shouldn’t necessarily be put in the same category as invasive lung cancers (pure BAC is a non-invasive lesion that shouldn’t be able to get into the bloodstream and spread outside of the lungs). And now, there’s a new article out of Japan that describes the experience of patients with BAC and multiple GGOs, some of which were resected and some not very accessible and some just watched. It turned out that just watching seemed to be a pretty good strategy.

The article out of Korea was published in the Journal of Thoracic Oncology and describes the experience of 73 patients with pathology-proven BAC, among whom 23 had other small GGOs identified pre-operatively. They followed patients after surgery for a median of 40 months and found that none of the patients with one or more identified small GGOs (<1 cm was their limit) showed any growth of these lesions; most stayed the same, and a few lesions actually regressed (they may not have been BAC and could have been inflammation or infection). They certainly had no impact on survival. Though the results are limited by the relatively short follow-up (just over 3 years of follow-up doesn’t mean people are out of the woods), they do suggest that it’s reasonable to use a watch and wait approach, at least for GGOs (which don’t have a solid component that suggests an invasive cancer) that are less than a centimeter (larger tumors are more likely to have some area(s) of invasiveness).

I’ve had several patients in whom there was one or a few growing lesions, perhaps with a solid component, along with several tiny background nodules that you aren’t sure how to manage. They may represent “multifocal BAC”, but often these areas are too small and inaccessible to sample. This work suggests that it’s appropriate to take your chances and ignore them.

In Japan and some other parts of Asia, the surgery they do for small BAC lesions is typically a wedge resection or segmentectomy rather than a full lobectomy, and this work is consistent with the idea that if you’re going to do surgery on small GGOs/proven BAC lesions, a complete lobectomy may remove far more good lung tissue than necessary.

To me, this work really raises the question of whether surgery is doing anything of value at all (at least if there are any other lesions left behind), if these lesions can sit there and do nothing for years at a time, and there’s only a finite amount of lung tissue someone can afford to lose to the scalpel or to disease (at some point in the future). While there is certainly a range of clinical behavior for BAC, I’m impressed with this evidence supporting a “less is more” approach and suggesting that these patients and their lesions may do well no matter what you do or don’t do.

Are we are Making Progress in Treating Non-small Cell Lung Cancer? You Bet! We all kno
BAC No More? The most e
A Disturbing Case of Needle Track Seeding from Biopsy of a Previously Resected NSCLC Tumor Several da

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Podcast by Dr. Camidge on ALK Rearrangements and a New Era of Molecular Oncology

Dr West — Fri, 26 Feb 2010 21:46:44 +0000

Last week, Dr. Ross Camidge from the University of Colorado joined me on a webinar entitled “One Size Does Not Fit All” in which he discussed the early work on ALK rearrangements and the novel agent PF-02341066 (now known as crizotinib) in particular, and the new era of molecularly defined practice of oncology in particular. This story has been widely considered to be among the most important in the field of lung cancer over the last few years, and Dr. Camidge did not disappoint.

Not only did many of the participants in the live program write comments here expressing their positive feedback on the great energy and overall quality of the program, but both our transcriber and the editor of our podcasts independently commented to me that they thought it was a terrific podcast and that they learned a lot (and they don’t have a special, vested interest in lung cancer issues).

Here’s the audio and video podcast links, as well as the transcript and the figures from the webinar:

dr-camidge-on-alk-inhibitors-and-molecular-oncology-audio-podcast

dr-camidge-on-alk-inhibitors-and-molecular-oncology-transcript

dr-camidge-on-alk-inhibitors-and-molecular-oncology-figures

Finally, I’d like to personalize this a bit, because one of the people who was mentioned in the podcast, Andy Hill, has also been featured in the local news in both Seattle (link to news report here) and Denver (link here) as a remarkable example of the promise of molecular oncology. He’s also been a dedicated and extremely helpful supporter of GRACE in terms of both financial support and participating in our recent programs and some meetings as we work on the future directions for our organization. So I’d like to dedicate the program to Andy and hope he continues to redefine the great success of this work in how well he does.

Speaking of which, we could really benefit from your support for these programs. This webinar wasn’t from a grant but rather from your contributions. I hope you find these activities helpful and will support them. I’d also encourage people to tell others, provide the link, if you know of anyone else who might benefit from learning the material in our educational programs. We’d hate to think of the Andy Hills out there who may miss a chance for a very helpful treatment because they simply didn’t know such a possibility might exist. And unfortunately, many oncologists are still not aware of these developments: the field is simply moving too quickly.

Comments or questions? We’d love to get your feedback.

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A New Series of March Webinars

Dr West — Thu, 25 Feb 2010 22:47:03 +0000

That short month of February makes it so that March really sneaks up on you! We’re just a few days from March and our first of several upcoming webinars I need to tell people about.

The first will actually be on Monday, March 1st (just 4 days from now), with Dr. Jared Weiss from University of Pennsylvania joining me at 8 PM EST/5PM PST for a discussion of two very different but timely topics. First, Dr. Weiss will cover the controversial and completely open question of what role EGFR inhibitors might play in early stage NSCLC, or whether we should even be talking about and checking for EGFR mutations in patients who don’t have advanced non-small cell lung cancer (NSCLC) (where most of the research and discussion has been concentrated). Next, I’ll turn to a debate that has been ongoing for decades in lung cancer: should the minority of patients with very localized small cell lung cancer (SCLC) undergo surgery? A very recent review of results from a large database put this topic back in the lung cancer news. So should SCLC ever be managed surgically? I’ll try to highlight the pros and cons.

Dr. Weiss and I will discuss our own perspectives on both of these issues and also leave time for questions from participants in the live online event. If you’re interested, you can’t beat the price of registration (free, though your financial support is very helpful), which is through this link: Register for the March 1 program with myself and Dr. Weiss

Oh, but it doesn’t end there. We received an educational grant from Eli Lilly in support of a couple of additional March webinars from terrific lung cancer leaders to cover very central topics in managing advanced NSCLC. On March 10th (again, 8 PM EST/5 PM PST), Dr. Suresh Ramalingam, medical oncologist and head of the Thoracic Oncology Program at Emory University in Atlanta, GA will cover “Personalized Therapy for First Line Treatment of Advanced NSCLC”. This approximately hour-long program will cover issues such as NSCLC histology (tumor subtype) safety concerns with anti-angiogenic agents, and the emerging work on molecular markers and how these factors lead to individualized recommendations for patients initiating treatment for advanced NSCLC, including an approximately 40-45 minute presentation, followed by time for questions from participants in the live program. Register for March 10th webinar with Dr. Ramalingam on Personalized Therapy Recommendations for First Line Treatment of Advanced NSCLC

A week later (Wednesday, March 17th at 8 PM EST/5 PM PST), medical oncologist Dr. Mark Socinski, who leads the world-renowned lung cancer program at the University of North Carolina at Chapel Hill, will cover “Optimizing Timing and Choice of Treatment after First Line Treatment of Advanced NSCLC”. Like the first line discussion by Dr. Ramalingam, this will be an approximately 40-45 minute presentation followed by Q&A, and Dr. Socinski will focus on the evidence supporting which agents are our strongest treatment options and how we might consider the question of whether patients should transition straight from first line to later treatment or whether a break from treatment might be a good idea. Register for March 17th webinar with Dr. Socinski on Timing and Treatment Choice after First Line Treatment for Advanced NSCLC.

Registration for each of these live events is limited, and we also know that the timing doesn’t work well for everyone who might want to be there, so all of these activities will be turned into podcast materials for people to refer to at any time in the future.

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Round Table Discussion with Experts: Indolent BAC in an Elderly Man

Dr West — Tue, 23 Feb 2010 06:09:45 +0000

This is the first part of a case presentation I did with two great colleagues: Dr. Anne Tsao, who is a medical oncologist and lung cancer expert at MD Anderson Cancer Center in Houston, and Dr. Alex Farivar, who is a terrific thoracic surgeon at my own institution, Swedish Cancer Institute in Seattle.

This case is an elderly gentleman who has a very indolent but growing lung lesion. His story brings up questions of how concerned to be in following a nodule in a patient of advanced age and with competing medical issues, whether surgery that is less than a lobectomy might be considered, as well as the systemic therapy options for bronchioloalveolar carcinoma.

Here are the audio and video versions of the podcast, along with the transcript and figures.

expert-round-table-tsao-and-farivar-pt-1-bac-audio-podcast

expert-round-table-tsao-and-farivar-pt-1-bac-figures

expert-round-table-tsao-and-farivar-pt-1-bac-transcript

I hope that’s helpful. We’ll provide info on a couple of additional cases from this discussion in the future.

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Loading the Dice: Comparative Trials of EGFR Inhibitors in Patients with EGFR Mutations (or, When Bad Trials Happen to Good People)

Dr West — Sat, 20 Feb 2010 05:30:55 +0000

The IPASS trial that randomized Asian never-smoking or light previously smoking patients with previously untreated advanced NSCLC to either standard chemo or the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) inhibitor Iressa (gefitinib) is widely considered among the most important and standard-changing trials of the last few years in the field of lung cancer. Nevertheless, it’s important to bear in mind that patients were identified for enrollment on that trial based on clinical factors, with about a third of the 1217 enrolled patients having their tumors analyzed for EGFR mutation status. The post-hoc results for that molecularly defined subset was the most interesting component of the trial, demonstrating that the patients with an EGFR mutation had a very significantly longer progression-free survival (PFS) with Iressa than with the standard chemo combination of carbo/taxol (paclitaxel). In contrast, the exact opposite was true for patients who were Asian never-smokers with an adenocarcinoma but didn’t have an EGFR mutation.

That comparison of chemo vs. an EGFR inhibitor in a clinically selected population was a perfectly appropriate question when the study was designed and enrolled, since we didn’t have evidence that one approach was superior to another in clinically or molecularly selected populations. This line of inquiry has been taken one step further by work from the North East Japan Gefitinib Study Group from Kobayashi and colleagues that tested Iressa against chemo in 200 previously untreated patients with advanced NSCLC who were prospectively selected for having an EGFR mutation. It was designed to enroll 160 patients per arm, but an interim analysis showed that the results were so overwhelmingly more favorable for recipients of Iressa that the trial was closed early because it was felt to be unethical to continue to randomize patients if the answer to the question was already clear. Although overall survival was not mature and wasn’t shown, preliminary results of this trial presented at ASCO 2009 revealed that the patients on the Iressa arm had a far superior response rate (74.5% vs 29%, p < 0.001) as well as PFS (10.4 vs. 5.4 months, p < 0.001). The curves for the latter are shown below.

(click on image to enlarge)

Along with this trial, a remarkably similar European trial is being completed that randomizes a population of previously untreated patients with an EGFR mutation to either erlotinib or cisplatin/docetaxel.

Between the recently closed Japanese trial and the ongoing European trial with a very similar design, I would say that there’s no more need for a new trial comparing an EGFR inhibitor to chemo in patients with an EGFR mutation. Still, there’s a new one recently activated, this time with a new agent known as BIBW 2992, or “Tovok”, from the large German pharmaceutical company Boehringer Ingelheim. BIBW 2992 has been hailed as a next generation targeted agent because it inhibits both EGFR (also known as HER-1) and another sibling receptor called HER-2 or HER2/neu, which is a very important target in breast cancer). Last year, some data emerged from a single arm trial of BIBW 2992 in patients with an EGFR mutation, and this showed that patients in this small trial had responses about half the time, which is similar to the results we’ve seen with the currently widely used EGFR TKIs Iressa and Tarceva, or perhaps less impressive. Still, the company wasn’t aiming high, and they achieved their modest goal of ballpark comparability with our currently available agents when the dice were loaded in their favor.

(this is how I think of this work)

Now, Boehringer Ingelheim is trying to run a trial called LUX-Lung 3, in which 330 patients with a lung adenocarcinoma and a proven EGFR will now be randomized 2:1 to their oral EGFR/pan-ERB inhibitor BIBW 2992 or cisplatin/alimta (pemetrexed). In a not very shocking turn of events, they’re having trouble getting patients enrolled globally, but especially in the US. After all, this is very similar to a trial that was closed in Japan because it was felt unethical to continue to randomize EGFR mutation positive patients to standard chemo.

While I can see why this trial would be helpful to the sponsor company, I can’t imagine a patient sending their tissue, learning that they have an EGFR mutation, hearing the rationale for giving a first line EGFR inhibitor and then willingly signing up to get chemo. What oncologist would feel comfortable randomizing such a selected patient to this? Even more impressive to me is that the principal investigator in the US is Mark Kris, Chief of the Thoracic Oncology Division at Memorial Sloan Kettering Cancer Center and one of the strongest proponents for aggressive EGFR mutation testing and first line use in the population of patients with an EGFR mutation. I believe that Dr. Kris is more likely to spontaneously burst into flames than to publicly declare that feels comfortable with the randomization in this trial and thinks it’s a perfectly great idea for previously untreated patients with advanced NSCLC who have an EGFR mutation to then knowingly have an EGFR inhibitor withheld. Tellingly, he hasn’t enrolled a patient of his own…

This is a trial that does not answer a relevant scientific question anymore. The proper trial for today would be one in which BIBW 2992 is directly compared to one of the more established EGFR TKIs to see whether it provides any improved outcomes, or if it happens to have activity in patients who have already received and progressed on gefitinib or erlotinib. But that trial isn’t being done, and instead the company is trying to get a drug approved by doing a trial that has essentially already been done and is known to subject some of the patients to a suboptimal treatment. Thankfully, doctors and patients are voting with their feet.

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Webinar with Dr. Ross Camidge: Learn about his Experience Treating Patients with EML4-ALK Translocation

Dr West — Mon, 15 Feb 2010 16:40:49 +0000

I just wanted to offer a reminder that Dr. Ross Camidge, medical oncologist and lung cancer expert from the University of Colorado in Denver, is going to be speaking with me during a webinar this Wednesday, 2/17, at 8 PM EST/5 PM PST. Among the topics we’ll cover is the EML4-ALK translocation, which is widely considered to be among the most exciting developments in the lung cancer field over the last several years.

Dr. Camidge was kind enough to agree to give a primer on the new and emerging story of EML4-ALK and the investigational drug PF-02341066, which Dr. Camidge was one of the first people to use in lung cancer patients. He’s currently treating some patients having sensational responses, so he can tell us more from the perspective of someone who has been directly involved with the research program.

We’re also going to cover a bit on the question of the role of surgery in more locally advanced NSCLC that is treated initially with chemo and radiation. I’ll present some background on this, including a new article that is coming out describing this experience. I’ll also invite Dr. Camidge to give some of his thoughts on this work as well.

Otherwise, we’re going to try to leave some time for questions on these subjects from people participating in the webinar. If you’re interested in being one of those people, please register for the Feb 17th webinar; registration is free but limited.

And because we know that some people who are interested in these topics may not be able to make the live event, we’ll also make this webinar into a podcast or two, so that people can access it later.

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Molecular Markers from the INTEREST Trial: Chemo and EGFR Inhibitor Therapy Still Remarkably Equivalent

Dr West — Sat, 13 Feb 2010 22:08:49 +0000

Oncologists often have their own ideas about how effective or ineffective a targeted therapy like an EGFR tyrosine kinase inhibitor (TKI) (Tarceva (erlotinib) or Iressa (gefitinib)) is compared with standard chemotherapy options. We’ve seen a lot of new information emerge in the field over the last few years, and we now have evidence that patients with an EGFR mutation generally have excellent outcomes with an EGFR TKI, but many physicians believe that patients who don’t have an EGFR mutation don’t get any benefit from this class of agents, or certainly far less than they get with a standard chemo agent.

The INTEREST trial directly compared Iressa with the standard chemo agent Taxotere (docetaxel), which was the first agent proven to improve survival for previously treated patients with advanced NSCLC. As I described in a post when the INTEREST trial was initially reported, this was a worldwide trial of 1466 previously treated patients with advanced NSCLC who were randomized to one treatment or the other, and I previously reported the results showing that Iressa and Taxotere led to an identical survival:

(click on image to enlarge)

That result is somewhat “interesting” (ugh..the horrible puns write themselves), in that

1) many people felt (and still d0) feel that chemo is simply more effective than a targeted therapy pill, and

2) Iressa actually didn’t show a significant improvement in survival compared to placebo in a trial of previously treated patients with advanced NSCLC, unlike Tarceva. So I might have expected equivalence of Tarceva with Taxotere, but if anything these results were better than I might have expected for Iressa in a population of patients who weren’t selected for having an EGFR mutation.

This brings us to the next point. The study also looked at the outcomes of Iressa vs. Taxotere in about a quarter of the patients who had tissue available for molecular marker testing. Many of us might have expected that patients with an EGFR mutation, and perhaps with EGFR gene amplification (by fluorescence in situ hybridization (FISH)) would do far better with Iressa than chemo, while some people have claimed that people with a KRAS mutation would get no benefit from Iressa and should do much better with chemotherapy.

The direct comparison of Iressa vs. Taxotere in different molecular marker subgroups is shown below. The right side of the figure shows progression-free survival, and the right side shows overall survival. The dots falling on one side of the vertical lines or another show a group doing better with Iressa (if the dot falls to the left) or with Taxotere (if the dot falls to the right), and the horizontal bars represent the uncertainty of where the real result could actually be (the smaller the group, the greater the uncertainty).

What these results show is that there are almost no differences in any groups, in that the dots pretty much fall close to the vertical line of equivalence, with the exception that progression-free survival was far better with Iressa in patients with an EGFR mutation. However, even in that group of patients most likely to do exceptionally well with Iressa, overall survival wasn’t different, probably because people with an EGFR mutation could end up doing just as well if they received an EGFR inhibitor later (and I suspect most did).

But there wasn’t evidence that other EGFR markers, such as the protein as measured by immunohistochemistry (IHC) or gene amplification as measured by FISH could discriminate which patients would do better with one approach vs. another, nor was KRAS mutation a useful tool.

The best answer may well be to try to give previously treated patients both chemo and an EGFR inhibitor over time, but there isn’t evidence to favor the order of one vs. another as a second line therapy. And for those of you asking why we shouldn’t combine chemo and an EGFR inhibitor together, there’s no evidence that this is a good idea, and there is even some suggestive evidence that these two approaches can interfere with each other. In the meantime, this work shows that it’s still dealer’s choice.

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Dr. Kristin Manning: Introduction to Imaging for Lung Cancer

Dr West — Thu, 11 Feb 2010 04:03:54 +0000

A radiologist, the person who specializes in reviewing imaging studies in medicine, is often someone you notice if they’re unusually bad or unusually good. They perform a service and you presume that they’re good at it, but a few are so sharp that the other doctors they work with notice it at every tumor board discussion or one on one exchange.

Dr. Manning is one of those special radiologists. She had trained at the University of Washington while I was completing my medical oncology training there, and when she left to join Seattle Radiology, a private group based at Swedish Hospital in Seattle, I was among the many doctors who felt the body blow of losing her talent. On the other hand, when I later joined the medical oncology group at Swedish, I was very happy to have the opportunity to be reunited with her.

But talk is cheap, so I’ll also add that when I developed a cough that lasted for months a few years ago, and one of the thoracic surgeons I work with said I needed to get a chest CT to check it out (as I joked that his practice was slow and that he was trying to drum up business), it was Dr. Manning who read my own scans for me (and fortunately, they were OK).

She remains a terrific resource, and one too valuable to not share with others. She was kind enough to sit down with me for a discussion of current issues in imaging, with a particular focus on issues related to lung cancer. Here’s the first part of our discussion, which covers a bit on screening, the issues related to assessing and following lung nodules, and some basics of the work-up and ongoing follow-up of patients with lung cancer. Below you’ll find the audio and video versions of the podcast, the transcript, and a copy of the very few figures associated with the audio component:

dr-manning-imaging-intro-part-1-audio-podcast

dr-manning-imaging-intro-part-1-transcript

dr-manning-imaging-intro-part-1-figures

I welcome your comments and questions. Part 2 of our discussion is coming soon.

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