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Lung Cancer FAQ: I’m coming to the end of my first line chemo for advanced NSCLC. After 4 (or 6) cycles are done, should I take a break or continue with some form of maintenance therapy?
The historic standard for advanced NSCLC up until a few years ago was for patients to complete 4-6 cycles of platinum-based doublet chemo, and then for patients who were doing well and had responded or demonstrated stable disease to take a break from treatment and be followed until progression. At that point, many patients would re-initiate chemo or targeted therapy with an oral agent like Tarceva (erlotinib).
Part of the premise was that ongoing treatment with challenging chemotherapy generally led to cumulative side effects, and at the same time, the limited work that had been done on fixed duration vs. ongoing chemotherapy until progression failed to show a significant improvement in survival with prolonged chemo, though it was associated with increased side effects.
Lung Cancer FAQ: I’ve just been diagnosed with advanced NSCLC. What treatment should I be starting with??
The initial or “first line” management of advanced NSCLC has evolved quite a bit over the past 10 years, in that time moving from a much more uniform approach of very similar treatment for just about everyone to a revised approach that is far more individualized. First, we assess key issues like the subtype of NSCLC, focusing largely on whether it is squamous cell or non-squamous NSCLC, because treatment tends to diverge very early based on this factor. Second, a patient’s performance status is another important issue, as patients who are frail often need a customized approach, because a more aggressive standard approach may be prohibitively difficult and even harmful. Third, a minority of patients (about 10% in North America and Europe, closer to 1/3 in Asia) will have a particular molecular marker, specifically a mutation in the epidermal growth factor receptor (EGFR), that is associated with a high probability of having a dramatic and long-lasting response to targeted therapy that inhibit the EGFR pathway. This particular activating mutation is most typically seen in never-smokers or people with a minimal, remote prior smoking history who also have an adenocarcinoma subtype of NSCLC.
Recommendations for first line therapy are most typically for a two drug chemotherapy combination, often with the drug Avastin (bevacizumab) — a targeted therapy that blocks the blood supply to the cancer — added for many patients who don’t have squamous NSCLC. However, for patients with an EGFR mutation identified before they have started treatment, several recent studies have demonstrated that the rate of significant tumor shrinkage and the time before the cancer progresses are significantly longer with an oral agent that works as an EGFR inhibitor, such as Iressa (gefitinib) or Tarceva (erlotinib). Consequently, one of these agents is increasingly recognized as a very appealing first line treatment approach.
Elderly patients are often treated the same as younger patients if they have minimal limitations in their activity level. In contrast, frail patients are sometimes recommended to receive single agent chemotherapy rather than a multi-agent combination that may be prohibitively difficult to tolerate. The available evidence suggests that elderly and frail patients who have an EGFR mutation also typically have a very significant response to EGFR inhibitor therapy.
Further information is available through the following links:
Podcast on introduction to first line chemotherapy for advanced NSCLC
Podcast on personalization of first line therapy
Reference library summary on selecting optimal first line treatment for advanced NSCLC
Using molecular markers to guide treatment: The IPASS trial
Alimta (pemetrexed) benefit is histology-specific
Treatment approaches for first line therapy in frail patients with advanced NSCLC
Podcast discussion of managing advanced NSCLC in the frail and/or elderly
Expert Round Table with Drs. Hensing & Jackman: Molecular Markers & Sequence of Therapy for An Asian Never-Smoker with Advanced Lung Adenocarcinoma
The third and final part of my conversation with Drs. Tom Hensing from North Shore Health System in Chicago and David Jackman from Dana Farber Cancer Institute in Boston covered a presentation of an Asian never-smoking woman with an advanced lung adenocarcinoma, the demographic picture most closely associated with potentially but not necessarily having an EGFR mutation or ALK rearrangement.
We cover the question of whether, in someone with a significant probability of one of these particular molecular markers, it’s worth obtaining tissue and delaying treatment to tailor treatment on the basis of these results. We also discuss the range of options for maintenance therapy in someone who has many alternatives for continuing one or more agents from the first line setting or switching to a new treatment. Finally, we turn to the question of managing treatment for a patient who has a prolonged response to an EGFR inhibitor and then develops an acquired resistance to that therapy.
Podcast: Play in new window | Download (47.4MB) | Embed
Local Therapy for Metastatic Disease: Why Might We Break the Rules?
One of the most common questions. we receive is why people are told that surgery isn’t an appropriate option for metastatic disease. If you can see the areas where there is active cancer, why can’t you just take it out?
The problem is that it’s very rare for a metastatic cancer to be limited to the areas that we can see. If a cancer spread from the lung to the liver, adrenal gland, brain, bones, or the other lung, it got there by having microscopic cancer cells (micrometastases) travel through the bloodstream to get there. Because this almost always means that there are many other micrometastases in the bloodstream, we’re fighting not just the cancer we can see, but the potential future areas of cancer we can’t see because they’re in the bloodstream, with the ability to settle in new places and grow into new lesions. So the general treatment strategy is systemic (whole body) treatment that travels through the bloodstream to reach cancer cells that may be distributed throughout the body.
Can An Early PET Scan Predict Response to Tarceva?
Over three and a half years ago, I wrote a post about about early work looking at the possibility that a PET scan done anywhere from three days to a month out from the start of a new systemic therapy (chemo or EGFR inhibitor) for advanced NSCLC could be predictive of a good outcome or not. Despite the increasing use of PET scans not only for staging but also for follow-up to assess response in patients with NSCLC, there hasn’t been a lot of new information since then. However, a study presented at ASCO 2010, coming from several Australian hospitals in collaboration with a couple in southern California, compared PET scans done after two weeks and then two months of Tarceva (erlotinib) therapy with the more established standard measure of response assessment, CT scans after two months of therapy.
Introduction to Locally Advanced, Unresectable Stage III NSCLC
When I was a medical student, the question about lung cancer that was always asked on “the Boards” had to do with the difference between stage IIIA and stage IIIB non-small cell lung cancer (NSCLC). The reason this question was always asked is because patients with stage IIIA NSCLC might be considered for surgery, whereas patients with stage IIIB NSCLC would not be considered for surgery and instead would be treated with chemotherapy and radiation. The idea is that young doctors should be able to make that distinction and to direct patients to the appropriate specialist/treatment. While I guess it makes a good test question, this distinction is too simplistic and doesn’t really give anyone a good understanding of the complexities of managing stage III lung cancer. And, in reality, all patients with suspected stage III lung cancer should be evaluated by a multidisciplinary team that includes thoracic surgeons, radiation oncologists, pulmonologists and medical oncologists. If the Medical Board would write a test question aimed at getting across this important principle, I’d breathe a big sigh of relief for lung cancer patients.
PF299804: Irreversible Pan-HER Tyrosine Kinase Inhibitor Showing Great Promise in Advanced NSCLC
We’ve received several questions about agents that might be helpful for patients who have already responded to inhibitors of the epidermal growth factor receptor (EGFR) like Tarceva (erlotinib) and Iressa (gefitinib) and then demonstrate progression. These latter agents are reversible inhibitors of of the tyrosine kinase domain (signalling portion inside the cell) of the EGFR molecule, meaning that they attach to and periodically detach from the receptor. Other inhibitors, like the novel Pfizer agent PF299804, bind to EGFR irreversibly, never coming off of the receptor, and requiring the cell to make new EGFR molecules without an inhibitor on them. Such agents can kill many kinds of cancer cells in a lab-based model, and appear that they may do so more effectively than currently agents like Tarceva and Iressa, but how well they work in real patients has remained an open question.
Another unresolved issue is whether PF299804, an inhibitor of not only EGFR but of other members of the human epidermal growth factor receptor (HER) family, of which EGFR (also known as HER1) is just one type, are more effective in patients than agents that inhibit EGFR alone. Such agents that block multiple members of the HER family are sometimes referred to as “pan-HER” inhibitors (as in “across the HER family“), but they’re still in clinical studies to determine whether such agents provide incremental benefit beyond what we see with the EGFR-specific agents we already use.
Though results with the orally available irreversible pan-HER inhibitor PF299804 weren’t a lead story at ASCO 2010, I think several of these trials were quite encouraging, both for patients with an EGFR mutation who might seek something after they become resistant to an EGFR inhibitor that previously was very beneficial, and also for people who don’t have an EGFR mutation and hope to do better than they might expect to do with an agent like Tarceva or Iressa.
Introduction to Small Cell Lung Cancer: Prevalence, Initial Symptoms, Work-Up, and Staging
General Introduction to Small Cell Lung Cancer
Lung cancer consists of two major types: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Approximately 85% percent of all lung cancer patients have NSCLC, and the remaining 15% have SCLC.
(click on image to enlarge)
In 2010, the American Cancer Society has estimated that approximately 222,000 new cases of lung cancer will be diagnosed, of which 35,000 will have SCLC. Even though both subtypes are lung cancers, they are considered as separate diseases in most ways, and the management of these two cancers is different. It is important to recognize that the treatments applicable for NSCLC, including many newer agents that have been approved and are the subject of increasing research and media attention, are not clearly relevant for patients with SCLC.
Physician Researcher Discredited, Potential Implications for Lung Cancer Research
Lest we think that media-driven self-immolation is reserved only for people Like Mel Gibson and Lindsey Lohan, this week we saw a little more drama than we prefer to see in the world of medical research, touching quite close to home. Following a rather stunning article in the low budget but tenacious Cancer Letter (primarily read by cancer and pharma/biotechl industry insiders), the New York Times ran a more widely publicized story about a highly regarded young researcher from Duke, Dr. Anil Potti, who allegedly lied about his being awarded a Rhodes Scholarship, and whose research on genetic signatures of lung cancer has recently been questioned after being published in the New England Journal of Medicine and several other very high-tier journals.
I know Anil, and he seems to be a good guy, but if the allegations are true, and it appears from the evidence, even if it’s not the type of evidence we usually discuss here, then he went too far in the more common practice of “resume padding” that so many people do by exaggerating their experience a bit or calling their student role a “pre-doctoral fellowship”. Not surprisingly, saying you won something as prestigious and verifiable as a Rhodes catches up with you, and his applications stopped mentioning this a few years ago, but it was too late. His reputation and the work he’s done at Duke have all been discredited, his research suspended, and a payments from a large grant of $729,000 from the American Cancer Society have been suspended.
SAIL Study Reviews Safety of Avastin in Lung Cancer Among >2000 Patients: Few Surprises (Fortunately)
This morning, Joe provided a link to a story about the Safety of Avastin in Lung cancer (SAiL) study, which is just being published in Lancet Oncology. This is not really a new, original study, but rather a post-approval commitment from Roche to generate a registry of real-life experience using the anti-angiogenic agent Avastin (bevacizumab) in lung cancer patients and document safety: the primary goal is to determine whether new, concerning safety signals occur in a broader clinical practice than the initial, well-controlled studies.
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