Lung Cancer / Mesothelioma
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Loading ...For many years, patients with malignant pleural mesothelioma (MPM) were often not offered treatment. Surgery was offered to rare, selected patients who tended to be much younger and more fit than a typical patient with MPM, but we’ll talk about surgery later. Chemotherapy was only very inconsistently offered to the vast majority of unresectable patients with MPM, because it was not felt to clearly be beneficial. This is pretty similar to the view of advanced NSCLC until the mid- to late-1990s. Fortunately, studies over the past several years have clarified that chemotherapy can improve survival for MPM.
Up until Alimta was approved, the regimen that was most commonly used for MPM was cisplatin and gemcitabine. This combination was reported in a trial of 21 patients with advanced MPM (abstract here) to produce an objective response rate of 48%, median response duration of about 6 months, and a median survival of about 9 month — not amazing, particularly in overall survival, but the best we had. In fact, several later trials suggested lower response rates and not as impressive results overall, but we used it because we wanted to help and patients needed treatment, and there had never been any reasonably large trials undertaken for MPM, so we really didn’t have any good evidence for or against the value of treatment. That changed when a large study evalauted the utility of cisplatin and alimta together.
At ASCO 2007, Nick Vogelzang and colleagues presented a plenary session abstract on mesothelioma (here) that was subsequently published as a full publication in 2003 (abstract here). The first major MPM trial ever, it enrolled 456 patients from 114 sites in 19 different countries. It had a straightforward design, randomizing patients to the likely minimally active cisplatin alone in one arm, and cisplatin/alimta in the other arm:
(Click to enlarge)
It was a plenary session presentation because the combination of cisplatin and alimta led to a significantly higher response rate (41% vs. 17%, p < 0.001), but also a significantly higher median survival by 3 months (12.1 vs 9.3 months, p < 0.02), as well as a nearly two month difference in median time to progression (5.7 vs. 3.9 mo, p < 0.001). The differences are shown here, with pretty striking differences (gaps) on the survival curves:
Impressive enough, but additional work (abstract here) also demonstrated that patients on the cis/alimta combination had significantly improved quality of life measures in terms of BOTH chest-related symptoms (chest pain, shortness of breath, and cough), and general (fatigue, loss of appetite, and activity level - the last not quite reaching statistical significance):
And so, based on this work, the US FDA approved Alimta for the first time as a treatment for MPM. Later that year, Alimta was also approved for lung cancer, but this represented a particularly big step in MPM, showing that this disease could be studied effectively and that treatments could offer significant benefits for patients with this too often ignored disease. And at this time, cisplatin alimta, or sometimes carboplatin substitution for cisplatin, are the leading treatment options for MPM.
Posted in: Lung Cancer, Mesothelioma
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Dr. West,
I’d like to dig the issue of Mesothelioma and again, ask for some help.
Indeed, this is a rare disease, proved further by zero comments on your four posts in this category. Unfortunately, one of my friends was selected to face this challenge. She has undergone 10 Alimta treatments so far, and now cancer showed resistance to it. We all strive to do something for her beyond comfort care.
Since I am not familiar with this disease or even medicine in general, please bear with me if I have any silly questions. After some searches, I found document says most patients with Mesothelioma have positive VEGF. Would VEGF inhibitors or other angiogenesis inhibitors work for Mesothelioma?
Is there any evidence or theory showing that EGFR inhibitors would work? Do you think Iressa or Tarceva worth a shot?
Thanks again for your help, Dr. West.
Ming
Ming,
Although mesothelioma is uncommon, and also not as well studied as we’d like, the slow progress hasn’t been for lack of trying. It’s a very tough cancer. There was a large trial that gave chemo with or without avastin, based on the hope that adding an antiangiogenic agent (VEGF inhibitor) would lead to a benefit. That trial was negative — no benefit seen. Even so, there are some other trials being done here and there around the country with other agents that also have anti-angiogenic activity. The Southwest Oncology group is close to starting a trial with a drug called RAD001, a drug in a new class called an “mTOR inhibitor”, for people who have received one line of prior chemo. This should be opening in the next few weeks, and many centers participate around the country in these trials. However, I’ve heard that this agent has challenging side effects, though I’ve never used it and don’t have much familiarity with what to expect.
Otherwise, the EGFR inhibitors have been tested and didn’t show any real promise of activity. Based on the quite disappointing results of this early work, larger studies with these agents haven’t moved forward in mesothelioma.
-Dr. West
There have been some trials of VEGF inhibitors in mesothelioma treatment (http://www.mesotheliomaweb.org/angio.htm) but so far the results have been less than great. (Which you could say about VEGF inhibitors in general.)
beren
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