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Management Approaches for EGFR Inhibitor-Induced Rash
After describing the association of a rash on EGFR inhibitors with overall better outcomes on this class of agents, we can now take a step back and recognize that the rash can be an annoyance at the very least and sometimes a real problem. While there are no established guidelines, both treating physicians and patients have developed experience with the rash over the past few years that we should be able to use to minimize the impact for the majority of patients and reduce the proportion of people who need stop a potentially helpful agent due to this toxicity. Continue reading
Old and New Approaches to Initial Treatment of Extensive SCLC
While progress in small cell lung cancer (SCLC) has been slow, over the past few years there have been leads in management of extensive disease that have introduced a potential change in the standard of care based on better results. Extensive disease SCLC, or ED-SCLC, is defined by having cancer that has spread outside of the region that can safely be covered by a radiation port (more details and relevant figure in SCLC 101 post), and this accounts for approximately two thirds of SCLC cases. Patients can often show very rapid cancer progression and clinical deterioration, but fortunately initial treatment very often leads to rapid and dramatic improvement, although we are not able to cure ED-SCLC.
Is Rash a Good Thing with EGFR Inhibitors?
An acne-like rash or dry skin is a very common side effect of the drugs that target the epidermal growth factor receptor, with approximately 3/4 of patients who receive the EGFR tyrosine kinase inhbitor tarceva/erlotinib experiencing skin toxicity. Similar skin toxicities are also seen, but a bit less commonly, with the very similar drug iressa/gefitinib, and also frequently with erbitux/cetuximab, a monoclonal antibody that is less well studied in lung cancer. But since the earliest clinical trials of these agents, there have been questions of whether the rash is something more than just a potentially problematic side effect, but rather a marker of someone likely to do well with these agents.
Small Cell Lung Cancer 101: An Introduction
After several weeks of posts on other aspects of lung cancer, I am long overdue to write on small cell lung cancer (SCLC). Although it is good to see the number of SCLC cases decreasing over time, and becoming a smaller and smaller percentage of lung cancer cases overall (only about 13% in the US and steadily falling), this has translated into fewer clinical trials and less of a focus on SCLC in the lung cancer community. However, there are some promising developments that may lead to some long overdue progress in the field.
First, this post will start with some general concepts and an introduction to SCLC, and this will be followed in the next few weeks by posts describing current and emerging ideas for the basic stages of small cell lung cancer, and also a discussion of prophylactic cranial irradiation for small cell, where it has been most extensively studied. Continue reading
Never-Smokers, Part II: Different Responses to Treatment
I reviewed some of the differences in the biology and clinical behavior of never-smoker lung cancers vs. the much more common lung cancer seen in current or former smokers. The main reason it is worth discussing is that there appear to be important differences in how never-smokers with NSCLC respond to some treatments, particularly EGFR tyrosine inhibitors like Tarceva, or Iressa previously. Among the first reports of this came from Memorial Sloan Kettering Cancer Center in NYC, which reviewed their experience with single-agent iressa several years ago and found that never-smokers were much more likely to demonstrate a significant response to iressa than current or former smokers (36% vs. 8% response rate, shrinking the cancer by 50% or more of the total measured volume). Along with bronchioloalveolar carcinoma histology, smoking status was among the most important variables in predicting response to iressa (abstract here).
As we learned about EGFR receptor mutations, first described in 2004 and associated with a high likelihood of response to EGFR inhibitors, we got some explanation for why never-smokers seemed to do well. In fact, the initial report by Dr. Lynch in the New England Journal of Medicine described 9 patients with excellent responses to gefitinib, of whom 6 were never-smokers. A study of tumor tissue out of Memorial Sloan Kettering showed that 7 of 15 lung tumors from never-smokers carried an EGFR mutation, compared with only 4 of 81 from smokers. Another study of patients who had surgery for early stage lung cancer in Japan showed that among 154 resected tumors (36% were from never-smokers, really highlighting how common never-smoker lung cancer is in Japan!). Since then, multiple trials have shown that never-smokers are significantly more likely to have EGFR mutations than smokers, and are also significantly less likely to have mutations in the gene k-ras (rhymes with mass) that in study after study are associated with no benefit from EGFR inhibitors. There are many controversial issues in lung cancer, but this is not one of them. From all over the world, the studies all show the same thing. Continue reading
Do Never Smokers with Lung Cancer Have a Different Disease?
Just a few years ago, the only distinction in the field of lung cancer that meant anything was small cell vs. non-small cell. The different types of non-small cell, like adenocarcinoma vs. squamous cell vs. large cell, were of little interest and didn’t change management (only a very recent development). And although we often asked about smoking history, the answer never changed our treatment plan. Only in the last few years have we come to recognize that we will do better as “splitters” than as “lumpers”, by tailoring our treatment recommendations to the clinical and molecular feature of one particular patient and tumor at a time, rather than using a one size fits all approach.
First, some definitions. Although there is a little variation, most of the lung cancer research community has come around to a definition of a “never-smoker” as less than 100 cigarettes in a lifetime. A “former smoker” is more than that and has quit smoking for at least a year. A “current smoker” is anyone else, so less than a year after quitting, a patient is still considered a current smoker. Continue reading
Avastin Studies Beyond its Current FDA Approval
As mentioned in prior posts, the anti-angiogenic monoclonal antibody Avastin (bevacizumab) is now approved in first-line treatment of advanced NSCLC in combination with carboplatin/paclitaxel chemotherapy. Among the very interesting questions is whether Avastin should be added with other active drugs for NSCLC. Most of us in the field strongly suspect that the survival benefit from Avastin will also be the case with other types of therapy, but we’re only starting to get the evidence to address this. Continue reading
Are EGFR Inhibitors Only Useful in Certain Patient Groups?
Since the earliest clinical trials of EGFR inhibitors in NSCLC, certain clinically defined patient subsets became identified as more likely to show a benefit than others. Such studies suggested that women, patients with adenocarcinomas rather than squamous cell carcinomas, Asian patients, and never-smokers compared with current or former smokers were the patients who would do well with EGFR tyrosine kinase inhibitors like gefitinib (Iressa) or erlotinib (Tarceva). Since that time, we have been debating whether these targeted therapies should be used primarily or exclusively in selected populations or whether they should be used in general lung cancer populations. The correlation of rash with better outcomes is another interesting issue that is a big enough topic I’ll discuss it separately in the near future. Since it’s not something you know about before you start treatment, unlike patient sex race or subtype of lung cancer, it’s a different issue.
Erlotinib (Tarceva) in Previously Treated NSCLC
In a recent post, I described the approval of taxotere as a second-line chemotherapy with a modest but survival benefit for patients previously treated with one line of chemo, usually a platinum-based doublet. Two years ago, erlotinib/tarceva, an inhibitor of a target on many NSCLC tumors called the epidermal growth factor receptor, was approved by the FDA as an additional treatment option for previously treated patients with advanced NSCLC, based on a large randomized clinical trial led by the National Cancer Institute of Canada that was published in the New England Journal of Medicine (BR.21 abstract here), demonstrating the importance of the results.
(Click to enlarge picture)
Treatment after Initial Chemo in Advanced NSCLC: Second Line and Beyond
Although we are all frustrated by the relatively slow pace of progress in lung cancer, there are times when we can look back and feel that we have made a real impact. Six years ago there were no treatments that were FDA approved and appeared to benefit patients who had previously been treated with first-line chemo for NSCLC. Now there are several. Continue reading
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