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My Top 5 Notable ASCO 2012 Abstracts in Metastatic NSCLC
The annual conference of the American Society of Clinical Oncology in late spring is the biggest event in the cancer world, where more of the big trials are presented than at any other time all year. In the lung cancer world, it’s looking like this one won’t be a blockbuster but will have some promising and interesting findings to discuss. As a preview, I wanted to offer my top 5 for what I think will emerge as the most important results we’ll see, based on the recently released abstracts of the meeting. Lung cancer is divided into two tracks: today, I’ll cover the metastatic lung cancer track, and then I’ll next offer a top 5 on the track covering stage I-III NSCLC, SCLC, and other less common thoracic cancers
Without further adieu, here are my top 5 in metastatic NSCLC: Continue reading
Questions about Benefit from Avastin in Older Patients
A group of investigators at Dana Farber Cancer Institute in Boston, MA recently published a very newsworthy article in the Journal of the American Medical Association (JAMA) that argues that patients with advanced non-small cell lung cancer (NSCLC) who are over 65 don’t appear to benefit from the addition of Avastin (bevacizumab) to standard chemotherapy with carboplatin/Taxol (paclitaxel). Several years ago, Avastin was demonstrated in the ECOG 4599 trial to lead to a survival benefit when it was added to carbo/Taxol in Avastin-eligible patients, who are a pretty limited subgroup with a good performance status, no brain metastases (a requirement since relaxed with more experience), no significant hemoptysis, and non-squamous NSCLC histology. However, there have always been elements of the story that have cast some doubt as to how much benefit it really offers, particularly in older patients. A subset analysis of the ECOG 4599 trial showed that patients over 70 experience disproportionately greater side effects and complications from Avastin and no survival benefit. Meanwhile, another large randomized phase III trial called AVAiL (AVAstin in Lung cancer) that was conducted in Europe showed a statistically significant but overall very unimpressive improvement in response rate and progression-free survival when Avastin was added to a different standard chemotherapy backbone of cisplatin and gemcitabine, and this study demonstrated no benefit at all in survival.
Since Avastin was approved by the US FDA in October of 2006, it has been considered a standard of care but not clearly the standard of care, and only about 20-25% of patients in real world clinics actually get it. The reason it ends up being given to only a minority of patients is a somewhat open question, but in truth, I think that when you disqualify patients with many of the clearer contraindications and then also factor in some relative contraindications such as a cancer next to major blood vessels or a poorly differentiated cancer that is suspected may be of squamous histology, the actual proportion of patients who are really strong candidates for it is probably below 40%. And then, there is also the question of how much stock clinicians place in the ECOG trial vs. the AVAiL trial that failed to show a benefit…and the fact that the median age of newly diagnosed lung cancer in the US is now around 71 meaning that a very significant fraction of patients with advanced NSCLC are in an age range where the value of Avastin is quite questionable.
Molecular Markers in Lung Cancer: Dr. Charlie Rudin on the Lung Cancer Mutation Consortium
This is the first of a series of podcasts from the two hour special webinar we did in partnership with the LUNGevity Foundation at the Santa Monica “Targeted Therapies in Lung Cancer” meeting several weeks ago. There, I was privileged to be joined by four excellent guest faculty members — Dr. Charles Rudin from Johns Hopkins University in Baltimore, Dr. Alice Shaw from Massachusetts General Hospital in Boston, Dr. David Spigel from Sarah Cannon Cancer Center in Nashville, and Dr. Glen Goss from the University of Ottawa. They each brought their rich experience and some differing perspectives on the complex and evolving topic of how to apply new work on molecular markers in lung cancer to clinical practice.
Below you’ll find links to the audio and video versions of the podcast, along with the transcript and figures.
Molecular Markers SM Pt 1 Rudin on LCMC Audio Podcast
Molecular Markers SM Pt 1 Rudin on LCMC Transcript
Molecular Markers SM Pt 1 Rudin on LCMC Figures
Podcast: Play in new window | Download (Duration: 17:36 — 40.6MB) | Embed
Refining Who Benefits with Erbitux: Can EGFR IHC Score Make a Stronger Case?
The FLEX trial, a European study of cisplatin/Navelbine (vinorelbine) with or without the monoclonal antibody against EGFR Erbitux (cetuximab), was a technically positive study that was initially reported at ASCO 2008. However, showing an improvement in median survival of just 1.2 months, most oncologists came away feeling that the trial illustrated the difference between a statistically vs. clinically significant result. Currently, the use of Erbitux in clinical practice is just a very small percentage of potentially eligible patients, though I think this would change if we could identify patients who are significantly more likely to benefit substantially and spare the others who actually don’t benefit from the cost, weekly infusions, and side effects of it. A recent report suggests that there may be such a method.
One of the most prominent presentations from the World Conference on Lung Cancer last month was a retrospective analysis of the results from the FLEX trial that divided patients based on the extent to which their tumor expressed EGFR protein on cancer cells as measured by the technique of immunohistochemistry (IHC). The investigators developed an “EGFR IHC score” that was a product of the percentage of cancer cells positive for EGFR protein on the cell surface multiplied by the overall intensity of staining (ranging from 0 to 3+), producing a number from 0 to 300.
(click on image to enlarge)
ASCO Highlights in Advanced NSCLC, by Dr. Nasser Hanna
Here’s the second talk from our recent webinar, partnering with LUNGevity Foundation to cover the ASCO Highlights in Lung Cancer, and this talk followed after the presentation by Dr. Mary Pinder on highlights in SCLC, early stage NSCLC, and mesothelioma and covered developments in advanced NSCLC. Dr. Nasser Hanna, an international leader in the field from Indiana University, summarized the most important new data in this arena.
Below you’ll find links to the audio and video versions of the podcast, as well as the transcript and figures from his talk.
hanna-asco-2011-highlights-advanced-nsclc-audio-podcast
hanna-asco-2011-highlights-advanced-nsclc-transcript
hanna-asco-2011-highlights-advanced-nsclc-figures
Podcast: Play in new window | Download (65.0MB) | Embed
The Evolving Role of Molecular Markers in the Management of Non-Small Cell Lung Cancer
The Importance of Identifying Molecular Markers in Non-Small Cell Lung Cancer
To understand the importance of molecular markers in the current and future treatment of lung cancer, one should first understand how lung cancer was classified up until the beginning of this decade. Pathologists would look at a sample of a patient’s lung tumor under a microscope, and then make a judgment of whether the cells represented small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC). Although that is an oversimplification, for all practical purposes, that is what oncologists cared about when it came to choosing treatment. If the diagnosis was NSCLC, then oncologists treated the patient with platinum doublet chemotherapy using one of many standard regimens that were felt to be equally effective. Unfortunately we knew that these regimens only worked in a certain proportion of patients, but we had no way to predict ahead of time who would benefit and who would not.
At the same time pathologists and molecular biologists have know for some time that NSCLC is not really just one disease, but rather a constellation of many diseases that all share the distinction of starting in the lung. For example, major subtypes such as adenocarcinoma, squamous cell carcinoma, and large cell carcinoma were often reported in pathology reports but did not influence treatment choice. Since 2004 we have taken this one step farther, asking pathologists to tell us not just that the lung cancer is non-small cell but also that it is non-squamous cell, for purposes of safety with Avastin (bevacizumab) and efficacy with Alimta (pemetrexed), but that is the topic for another chapter.
As our understanding of the molecular basis of cancer has grown, we have developed a number of new molecularly-targeted agents with promise in the treatment of lung cancer. However, targeted drugs tend to have limited or no effect on cancers that lack the “target” of the drug, creating a need for markers to guide us.
Lung Cancer FAQ: My advanced NSCLC has progressed after initial chemo. What are the leading options now?
In the last decade, the treatment of NSCLC has evolved very significantly, and one of the leading ways has been that we’ve gone from having no established role for treatment after initial, first line therapy to having multiple agents with a proven benefit.
It’s worth clarifying that as maintenance therapy is increasingly being considered as an option after first line therapy, a distinction between this and second line therapy. Maintenance therapy is given to prolong the period before someone who has achieved a response or stable disease on first line treatment demonstrates progression for the first time, while second line therapy is the term more commonly reserved for treatment after someone has demonstrated evidence of progression for the first time after first line therapy.
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.
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
Expert Round Table with Drs. Hensing & Jackman: Molecular Markers & Sequence of Therapy for Stage IV Lung Adenocarcinoma
The second 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 case of a relatively young, generally healthy woman diagnosed with a lung adenocarcinoma that turned out to be stage IV.
Here, we discuss our priorities for molecular testing and how the results of EGFR, KRAS, and EML4-ALK testing would alter our clinical recommendations. We then discuss the options for this patient, with special focus on how long to continue first line therapy and when and how to transition off of first line treatment into either observation or maintenance therapy.
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