There’s a problem in our discussions of standard treatment for patients with higher risk resected early stage NSCLC, and that is that there is a pretty clearly defined standard of care of giving typically around 4 cycles of cisplatin-based chemotherapy to reduce the risk of recurrence, but in truth, the majority of people in the real world don’t get it.  Still, I wouldn’t want to imply that the problem is definitely that doctors aren’t giving the right treatment to people who should definitely be getting it.  I’m concerned that the problem may be that the well defined, trial-defined standard of care may truly not be the ideal choice for the majority of patients.

The median age of patients in all of the trials that give adjuvant chemotherapy is 59-63, which is a decade younger than the median age of a patient newly diagnosed with lung cancer in the US.  Even looking at younger patients, a very substantial fraction have other medical problems or aren’t doing and feeling very well 4-7 weeks after a big lung surgery, which is when we’d usually want to give it.  Many have kidney function that isn’t great, hearing loss, or some other good reason to not get cisplatin.  So when we actually look at the treatments early stage NSCLC patients actually get, a huge fraction get no chemotherapy even if they would otherwise technically be a candidate based on the pathology findings, and the most commonly used regimen in the US is carboplatin/Taxol (paclitaxel), a regimen that has been tested as a post-operative therapy and failed to show a survival benefit, relegating carboplatin-based adjuvant chemotherapy to second tier status, below cisplatin-based chemo.

Last weekend, I gave a summary of some ASCO Highlights in lung cancer at a meeting for oncologists, and I was charged with reviewing some of the adjuvant therapy results from this year, including a trial called TREAT that Dr. Pinder covered in our own webinar on ASCO Highlights in Lung Cancer, and which asked the question of whether cisplatin/Alimta (pemetrexed) might be a regimen more feasible to administer than the most data-supported option of cisplatin/Navelbine (vinorelbine).  The background of that trial is that the existing trials with the cisplatin/Navelbine regimen show that in some studies, more than half of the people came off of treatment before getting through it, and huge proportions of patients need to delay or stop treatment due to prohibitive drops in blood counts or some other toxicities, or they simply refuse to continue with more treatment.  I’ve certainly seen this in many of my own patients, on or off of a clinical trial — even if they know that there is a potential survival benefit to be gained, some express that they’d rather be dead than to continue on cisplatin-based chemo.  The trial actually confirmed that the cisplatin/Navelbine regimen as best studied is quite difficult to administer on any kind of regular schedule, at least without it being a soul-crushing experience; cisplatin/Alimta was more feasible, though not a cake walk itself either.

More concerning to me is the fact that, if you pool many of these older trials together, around 1% of patients die as a result of adjuvant therapy.  Let me remind you that these are people who already have a significant chance of being cured.   There is also some work from longer term follow-up in adjuvant therapy trials that suggests that the survival benefit from adjuvant chemotherapy in the first few years may be compromised by higher death rates in recipients of chemotherapy more than 5 years out, compared with observed patients.  Also of concern are the preliminary findings of the ongoing 1505 trial of cisplatin-based chemo with or without Avastin (bevacizumab) reveal that while there isn’t a statistically significant increase in serious side effects with addition of Avastin, the rate of treatment-related deaths on the two arms is 2.5% with chemo alone, and 3.8% with Avastin.   [NOTE: Since writing this, I have learned from Dr. Suzanne Dahlberg, statistician for ECOG, that these numbers are not specifically attributed to treatment but could be from other causes, such as treatment-related recurrences.  This is quite reassuring, as the quoted numbers were higher than I'd expect or hope to see for treatment-related deaths a multicenter North American experience.] Read the rest of this entry »

Several weeks ago, we were fortunate enough to have Dr. Mary Pinder (alternately referred to as Pinder-Schenck) from the H. Lee Moffitt Cancer Center in Tampa join as the first of two speakers reviewing highlights in thoracic oncology from ASCO.  She covered several key presentations in small cell lung cancer, early stage non-small cell lung cancer, and mesothelioma.   Here’s the audio and video versions of the podcast, along with the transcript and figures (a zip file to decompress, since it was too big in unzipped form to upload) for this program:

pinder-asco-2011-highlights-sclc-early-stage-nsclc-and-meso-audio-podcast

pinder-asco-2011-highlights-sclc-early-stage-nsclc-and-meso-transcript

pinder-asco-2011-highlights-sclc-early-stage-nsclc-and-meso-figures

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Continuing with this series of case-based podcasts we’ve done  in partnership with LUNGevity, we’ll again have a series of experts offer their own perspective to another challenging scenario.  All are with the same format of me hosting and presenting the case to Drs. Bob Doebele from University of Colorado and Jyoti Patel from Northwestern University, who participated in the live webinar version of this, then followed in the recording by other terrific colleagues of mine weighing on the same case.  These experts are:

• Dr. Suresh Ramalingam, from Winship Cancer Center, Emory University in Atlanta, GA,
• Dr. Jonathan Goldman, from Premier Oncology in Santa Monica, CA.
• Dr. Julie Brahmer, from Sydney Kimmel Cancer Center at Johns Hopkins University, in Baltimore, MD
• Dr. Heather Wakelee, from Stanford University Cancer Center in Palo Alto, CA
• Dr. Karen Reckamp, from City of Hope Cancer Center in Duarte, CA

This case is of a woman with a tumor that is in the range that is smaller than that for which we would routinely recommend post-operative (adjuvant) chemotherapy to reduce the risk of recurrence, but the tumor has some higher risk features that lead her, and might lead us, to be more inclined to recommend it despite the smaller size of the tumor (which is still within a pretty debatable range).  Here’s the links to the audio and video versions of the podcast, along with the transcript:

adjuvant-chemo-for-smaller-nsclc-tumor-with-high-risk-features-audio-podcast

adjuvant-chemo-for-smaller-nsclc-tumor-with-high-risk-features-transcript

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This is the first of a series of podcasts we’ve done, developed in partnership with LUNGevity Foundation, in which I present the same challenging cases in lung cancer management to a series of experts to learn the range of views offered by them, then the multiple thoughtful comments by all of them discussing the same single featured case for each podcast.  The first discussants in each podcast will be Drs. Bob Doebele from University of Colorado and Jyoti Patel from Northwestern University, who are then followed by other terrific colleagues of mine:

• Dr. Suresh Ramalingam, from Winship Cancer Center, Emory University in Atlanta, GA,
• Dr. Jonathan Goldman, from Premier Oncology in Santa Monica, CA.
• Dr. Julie Brahmer, from Sydney Kimmel Cancer Center at Johns Hopkins University, in Baltimore, MD
• Dr. Heather Wakelee, from Stanford University Cancer Center in Palo Alto, CA
• Dr. Karen Reckamp, from City of Hope Cancer Center in Duarte, CA

Our first case is a discussion of how they would approach a patient who has a small primary tumor that also has a separate microscopic satellite lesion nearby.  Here’s the links to the audio and video versions of the podcast (there isn’t a lot of video to see, by the way), along with the transcript:

case series: small nsclc tumor w/satellite lesion video podcast

case series: small nsclc tumor w/satellite lesion audio podcast

case-series-small-nsclc-tumor-wsatellite-lesion-transcript

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The staging of lung cancer makes the distinction of whether there are any lymph nodes involved with cancer, and if so, whether they are within the lung that houses the primary cancer or outside of it; if the latter, a distinction is made among mid-chest nodes on the same side as the main tumor (N2), mid-chest nodes on the opposite side from the main tumor (N3), or above the collarbone (N3).  This staging is described in more detail in a summary chapter in the lung cancer reference library on initial workup and staging of lung cancer.

But there may also be useful distinctions to be made.  I’ve previously described some investigational work suggesting that the number of lymph nodes involved may have prognostic value.  Another concept that is commonly accepted is that the risk of recurrence is lower if a patient has a lymph node involved just by direct extension of the cancer into an adjacent lymph node, as opposed to spread to lymph nodes that are some distance away from the primary tumor and therefore presumed to have spread through lymphatic channels.  A Japanese study reviewed results in patients with resected early stage NSCLC and N1 nodal disease in order to address this question.

A prior publication by the same group from earlier this year looked at outcomes from just patients with squamous NSCLC who underwent surgery and had N1 disease as their highest stage.  Among the 120 patients with N1 nodal disease, the 5-year survival was 67.7% in those with just direct extension, compared with the significantly inferior 5-year survival of 32.4% in those with distant spread, a result that was comparable to that seen in patients with N2 nodal involvement. The current effort looked at a much larger group of 324 consecutive patients with pathologically confirmed N1 nodal involvement, including patients with both squamous and adenocarcinoma histologies.  They compared these results to those of 1524 patients with node-negative disease, and 330 others with N2 nodal disease (N3 nodal involvement is generally considered to not be best managed with surgery).  The investigators reviewed whether there were differences in the overall NSCLC population and also looking specifically at the histology of the NSCLC tumor, as squamous tumors have a tendency toward more local spread and adenocarcinomas tend toward earlier spread to distant sites, although these are only general tendencies.

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   Here is a continuation of the webinar discussion I did with Dr. Pennell a month ago, in which we discussed some of the most interesting presentations on lung cancer at ASCO 2010.  Although the most provocative results were the negative results on the BR.19 trial that suggested a potential detrimental effect of the oral EGFR inhibitor Iressa (gefitinib) after surgery, there was also a trial on early stage NSCLC that was more favorable, even if it didn’t reach statistical significance for a survival benefit.  This trial focused on pre-operative, or neoadjuvant, chemotherapy.  Here’s the transcript with associated figures (admittedly similar to a prior post on this subject):

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Dr.  West:       So, I’m going to turn briefly to an update of a trial that was actually published years ago and this was a study of generally pre-operative therapy with an older regimen called MIP, or MIC, for mitomycin C, ifosfamide, and cisplatin. And most of the people who have been following our discussions of treatment options in non-small cell have little or no familiarity with at least the first two of those agents, because they have beenvery uncommonly used over the last decade or so, having been replaced by newer therapies. Nevertheless, this is an older study and what this study looked at was the long-term, now with more than 10-year follow-up results of pre-operative chemo followed by surgery versus surgery alone. 

 (click on image to enlarge)

Some of the patients, if you had responded to the pre-operative chemo, would get an additional two cycles, and in Europe they still do a fair bit of radiation for locally advanced disease. 

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It’s been a few months since I sat down with my friend, Dr. Nasser Hanna, a great lung cancer expert from Indiana University, and also a friend in the field. Those of you who have been following GRACE content for a while may have come across his name: he’s led a few of the more important trials that are part of our current core knowledge in lung cancer now, such as the trial that directly compared Alimta (pemetrexed) to Taxotere (docetaxel) as second line therapy for advanced NSCLC; the Hoosier Oncology Group (HOG) trial that showed no benefit to consolidation Taxotere after chemo/radiation for stage III NSCLC; a trial of maintenance therapy with oral etoposide after initial cisplatin/etoposide for extensive stage small cell lung cancer, as well as others.

Here’s a transcript and a few key images from our discussion of a challenging case of an elderly woman considering the merits of post-operative chemotherapy for stage IB NSCLC. (I’ll just note that this format of presenting a transcript and a few figures is a fast, cheaper way for us to present the content of conversations we’ve been turning into podcasts until this point. It may be easier to just have it here online, and cuts our costs.  If you have a definite preference for the audio/visual format of a podcast vs. this, please voice that opinion).

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Dr. West: Hi, I’m Jack West, Medical Oncologist and President of GRACE, The Global Resource for Advancing Cancer Education. I’m here today with Dr. Nasser Hanna who is Associate Professor in the Department of Medicine, a Medical Oncologist at Indiana University and he was good enough to sit with me and talk about a few complex cases, so thanks for taking the time.

Dr. Hanna: Thanks for having me.

Dr. West: Let’s start with a challenging type of situation that isn’t rare in the adjuvant setting.  I saw a 73 year old woman…use to smoke up to a couple of packs per day for fifty years and brought her self down to a few cigarettes per day.  She has a good performance status and several months ago developed a worse cough, productive of some clear sputum, no hemoptysis and she was prescribed antibiotics but didn’t get better.

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Introduction to Adjuvant Therapy: Why More than Just Surgery?

For patients with early-stage non-small-cell lung cancer (NSCLC) (stages I, II and some III), surgical resection (removal by surgery) is the standard treatment. Unfortunately, the rates of recurrence (cancer returning) after resection can be high, and additional therapy (chemotherapy) can improve the odds that the cancer won’t return for some patients. This article goes through the data we have that demonstrate the benefit of chemotherapy after surgery for early stage lung cancer, information about chemotherapy before surgery, new treatments being studied for lung cancer patients after surgery and ongoing studies to help better determine which patients might benefit the most from particular treatments.  We have learned about the importance of chemotherapy and other treatment after surgery from patients who were willing to go on clinical trials.  Patients on the trials either received new treatments or were randomized (assigned by chance) to either get chemotherapy or not after surgery.  The information below comes from the analyses that have been done of the patients who were willing to participate in clinical trials.

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I’m proud to say that many years ago I sent Dr. Heather Wakelee from Stanford a set of my slides on post-operative therapy for early stage NSCLC — we’ ve been friends since we were both getting started in our careers.

Flash forward several years, and now she’s among the national leaders in the field of adjuvant therapy for NSCLC and leads one of the most important trials in that setting — the ECOG 1505 trial that is testing whether there is a benefit of adding the anti-angiogenic agent avastin (bevacizumab) to standard chemo after surgery.  She was kind enough to come up from the Bay Area to participate in the GRACE NSCLC Patient Education Forum back in September to provide a brief synopsis of our understanding of the current best strategies for post-operative treatment of patients with resected NSCLC.    She also did a recent podcast on the overlapping subject of clinical trials in the adjuvant setting as part of an educational grant, , but this program is a more general overview.

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GRACE is very happy to have the opportunity to present this podcast by Dr. Heather Wakelee, medical oncologist at renowned lung cancer expert at Stanford University Cancer Center.  The focus of this particular program, supported by an educational grant from GlaxoSmithKline, is on the most important research questions and clinical trials in the field of post-operative therapy for resected NSCLC.

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