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New Year, New Stats
Happy new year, GRACErs! The change in the calendar brings out contemplation. Most of the year, the gym in my building is quiet and hardly used so I can calmly read my journals on the exercise bike. The exercise hopefully compensates for my otherwise sedentary, nerdy lifestyle and I find that I do good thinking there. Now, after the new year, as in every year, the gym has been briefly very busy. During an otherwise not so impressive workout, I read an article that I think may be of interest to some in this community.
The Journal of Clinical Oncology rang in the new year with a review of our advances and failures entitled: “Clinical Cancer Advances 2009: Major Research Advances in Cancer Treatment, Prevention, And Screening—A Report From the American Society of Clinical Oncology”. The statistics are a bit depressing so for those who prefer to avoid these numbers, please stop reading. I promise not to be offended and will write more stuff without stats for you. For those who find these statistics interesting and useful for advocacy, feel free to read on.
Round Table Case-Based Discussion — Drs. Laskin and Sandler on Molecular Testing in a Never-Smoker
Here is the first podcast of what we plan will be an ongoing series of round table discussions with cancer experts about real case scenarios and how we make decisions in practice. My guests for the discussion are Drs. Janessa Laskin, medical oncologist from British Columbia Cancer Agency in Vancouver, BC, and Alan Sandler, medical oncologist and Director of Hematology/Oncology at Oregon Health & Science University in Portland.
The first case we discussed is a relatively young Asian never-smoking woman with an advanced lung adenocarcinoma, focusing first on the changing standards for sending tissue for molecular testing, as well as the limitations of that. Here is the video version, audio, transcript, and associated figures.
round-table-laskin-sandler-never-smoker-mutn-testing-audio-podcast
round-table-laskin-sandler-never-smoker-mutn-testing-transcript
round-table-laskin-sandler-never-smoker-mutn-testing-figures
Podcast: Play in new window | Download (0.3KB) | Embed
A new tyrosine kinase inhibitor to overcome resistance to T790M?
LM is a 73 year old patient of mine. She typifies the idea of functional age over chronologic age —physiologically, she’s more like a 50 year-old and remains extremely active despite having had lung cancer since the spring of 2006. The targeted therapy Tarceva (erlotinib) was her first treatment, which worked for over two years. She was then treated with three different cytotoxic chemotherapy regimens, with a theme of response followed by progression. Each time, the progression was caught on imaging before she suffered any bad cancer symptoms, and treatment with each of these three regimens went well, with fairly minimal side effects.
This strategy worked for a year until this summer, when she progressed again. We switched her therapy to taxol (paclitaxel), with the thought that she might again respond with minimal side effects. Unfortunately, she suffered from a low white blood cell count (neutropenia) and severe fatigue. We then tried navelbine (vinorelbine), but she progressed. She is very motivated for additional therapy but wishes to avoid cytotoxic agents. Because she is an Asian never-smoker with an adenocarcinoma and a history of two-year response to Tarceva, I assume that she had a mutation in the epidermal growth factor receptor (EGFR) and then developed resistance. Are additional agents available to her?
What I really do: Molecular testing for NSCLC
I’m fortunate to practice at Moffitt, where Dr. Gerold Bepler and Dr. George Simon pioneered a molecularly directed approach to front-line chemotherapy in NSCLC. Data from the phase II clinical trial demonstrated impressive median survival for a platinum-based doublet: 13.3 months. The schema of the MADeIT clinical trial is shown below and I’m happy to say that I am able to put many of my patients on this clinical trial. Dr. West recently posted a podcast featuring Dr. Simon, where he describes the trial in more detail.
(click on image to enlarge)
The testing for ERCC1 and RRM1 is performed at Moffitt and turnaround time is typically around a week or less. I consider this a very reasonable interval since patients are unlikely to experience progression or declines in their performance status in a week. A sample from a prior biopsy can be used and fresh tissue is not required. Even when we have to obtain tissue from another institution, we can usually get the patient started in a very reasonable time frame. Right now, we only perform testing as part of the clinical trial. I think this is the right thing to do: although our hypothesis is that molecularly-directed therapy will be superior, we don’t know that for sure yet.
Dr. Julie Brahmer on Second Line Therapy: What Treatment and When?
The last of our podcasts in 2009 will also close out the series of presentations given at our September NSCLC Patient Education Forum here in Seattle, which was sponsored by OSI Pharmaceuticals and Swedish Cancer Institute (thanks!). The forum covered everything from initial workup to management principles of early stage NSCLC, locally advanced disease, and advanced/metastatic NSCLC. Dr. Brahmer, a friend for many years now who is a medical oncologist and lung cancer expert at Johns Hopkins University in Baltimore, spoke on treatment of patients after the first line setting, integrating thoughts on both patients who have progressed and also the emerging information on maintenance therapy for patients who have stable disease or have shown tumor shrinkage and no progression after the first line setting.
Her presentation is here, including both the video and audio podcast versions, and the accompanying transcript and figures.
brahmer-second-line-therapy-treatments-and-timing-audio-podcast
brahmer-second-line-therapy-treatments-and-timing-transcript
brahmer-second-line-therapy-treatments-and-timing-figures
Podcast: Play in new window | Download (49.0MB) | Embed
Women, Tamoxifen, and Lung Cancer
One of my areas of interest is studying gender-related differences in lung cancer. Earlier this year, I wrote a post about interesting data that had come out of the Women’s Health Initiative study. This was the landmark study that established that hormone replacement therapy (HRT) for postmenopausal women did more harm than good. When originally presented in 2002, the investigators noted significantly increased risks of breast cancer, cardiovascular disease and stroke. At ASCO 2009, they also reported an increase in lung cancer incidence and lung cancer mortality among postemenopausal women who received HRT compared to those who received placebo.
(click on image to enlarge)
Vorinostat for NSCLC: Not a home-run, but at least swinging for the fences
Substantial resources are spent on large, expensive trials to demonstrate small survival advantages in lung cancer. For example, 889 patients entrusted their care to the phase III SATURN trial of maintenance erlotinib, following treatment with a platinum doublet. At ASCO, we learned that these patients were rewarded with a one week improvement in PFS, and at World Lung, we learned that they lived a month longer. The FDA’s advisory committee recommended against approving erlotinib for maintenance therapy based on this modest benefit.
I am among many oncologists who take a two-faced view on small advances in care. On the one hand, I use advances with modest benefits in my clinic. I do not consider financial cost/benefit when adding avastin to platinum-based doublet therapy for patients with non-SqCC; I even use cetuximab, with more modest benefits, at times. While I use these small advances regularly in my clinic, I take a very different perspective when talking to other investigators, where I argue that we should be swinging for the fences, not trying to get more base-hits. Along the way, we will make minor advances and should use them, but the real goal should be to either cure cancer, or develop non-toxic drugs capable of turning cancer into a chronic disease.
With this perspective in mind, agents that can potentially overcome resistance in lung cancer are of particular interest to me and the histone de-acetylase inhibitors fit this mold. As I am working on a trial of a histone de-acetylase inhibitor for small cell lung cancer, these agents were already on my mind when I read the results of a new study in JCO.
Picoplatin for SCLC — Another One Bites the Dust
A few weeks ago, I received an email from a colleague at an affiliated hospital with the title, “Another one bites the dust.” Now I love Queen as much as the next guy, but I don’t like seeing this line in reference to new oncology drugs. In this case, the drug was picoplatin.
Picoplatin is a novel platinum drug, somewhat like cisplatin or carboplatin. Like most chemotherapy, it works by poisoning DNA, causing rapidly dividing cells to die. As you can see, it shares the common platinum core with our old “friend” cisplatin, but the shape has been modified. The idea was that the drug might work in tumors that were resistant to cisplatin.
Picoplatin
Cisplatin
Picoplatin looked good in early studies, even earning attention on GRACE. Last year, Dr. West outlined the vital stats for the phase II of 77 patients for this new compound in 2nd line SCLC:
- Good side effect profile
- 10% response rate
- Median progression-free survival of 10 weeks
- Median survival of 27 weeks
Lung Cancer Screening: Dr. West shouldn’t be the only one with a bulls-eye on his chest (and no, I don’t torture puppies either)
On March 24, 2009, Dr. West wrote,
Lung cancer screening is one of my least favorite topics to discuss because it’s probably one of the biggest areas where there is a gulf between the medical establishment’s party line and the expectations of many patients and advocates. I tackled a discussion of screening a few years ago that included the anticipated benefits as well as the challenges with LC screening (nowadays really focusing on low dose, spiral CT). That was probably about the most frustrating topic I’ve pursued, initially heralded after my post on the arguments in favor of screening, but feeling like I was being vilified as a kitten torturer in the responses I received after my post about the thorny issues with it.
Dr. West’s last post is relevant to the conversation that member cards7up and I have been having on the discussion thread from my piece on November 30, 2009. The gist of the conversation is about whether to screen, and if so, how to do it.
On the “if” question, I consider my father’s desire for pan-scans to look for occult cancer (he quit smoking about 20 years ago). Every now and again, he hears on the radio ads for commercial enterprises offering pan-scans for a fee to screen for cancer. Even though he can afford it, I don’t let him go—I feel that he’s more likely to be harmed by the test than helped. Dr. West addressed this issue in his discussion about PSA and prostate cancer:
But last week, the story emerged that PSA screening for prostate cancer appears to provide somewhere between little and no survival benefit for men. One large trial suggested a very small benefit, in which nearly 50 patients would need to be treated to save the life of one from prostate cancer, and another trial didn’t show a survival benefit. After lung cancer, prostate cancer is the next most common focus of my practice, and I can assure you that I find this very easy to believe. I see many men who are exceptionally likely to do well, begging the question of whether they underwent surgery or radiation or some other alternative for no benefit, but who have had a permanent compromise of their sexual function, urinary continence, and other issues important to their quality of life (and I probably see only a small minority of the patients who are exceptionally likely to do well and never even see an oncologist). I also see men with prostate cancer who undergo aggressive treatments for prostate cancer but have a virulent enough cancer that even screening efforts and timely, aggressive interventions can’t save them from their cancer. In between, the numbers suggest one in 50 men may be saved from a truly life-threatening cancer.
Debating maintenance therapy for advanced NSCLC: Not accepted as the standard of care
This past weekend, I had the unenviable task of debating my friend Dr. Nasser Hanna, from Indiana University and a highly respected leader in lung cancer, about maintenance therapy. He had been the expert discussant of the three key trials on maintenance therapy presented at ASCO this year (the JMEN trial of Alimta (pemetrexed) and the SATURN and ATLAS trials that evaluated Tarceva (erlotinib). These trials were all “positive”, all showing a significant improvement in progression-free survival, and the JMEN trial showing a significant improvement in overall survival (the SATURN trial was also later reported to show a significant improvement in overall survival, but those results weren’t available at ASCO, the leading oncology meeting of the year. Each of these trials supported the concept of transitioning immediately from first line therapy to a new therapy after four cycles, or adding a new agent to maintenance Avastin (bevacizumab), but Dr. Hanna added thoughtful commentary and made a convincing argument that the results from these trials weren’t strong enough to make maintenance therapy as standard of care.
So it was likely in the role of the sacrificial lamb that the I was invited by the organizers of the conference to argue the “pro” side in favor of maintenance therapy as the new standard. Trying to rise to the challenge and ignore the potential of being humiliated by my silver-tongued opponent (so polished that he’s running for Congress in Indiana in the next race), I took the bait. Though I’d had a good run and won several prior light-hearted debates on controversial topics in lung cancer in the last few years, Dr. Hanna ate my proverbial lunch: the audience, already disinclined toward maintenance therapy prior to the debate (as demonstrated by the pre-debate baseline question), moved further away from the concept after hearing our arguments. The chairman of the meeting, moderating the discussion that followed, felt a need to publicly note that he felt that my talk was more compelling than the numbers suggested.
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