Abraxane Bests Taxol in Response Rate for NSCLC: What Might this Mean?

In addition to developing new agents or refining which patients should or shouldn’t be given to particular patients, another way to potentially gain ground in fighting cancer is to improve the tolerability of a standard treatment in a way that either makes it more effective or reduces side effects, thereby making it possible to give higher doses.  The drug Abraxane (nanoparticle albumin bound paclitaxel) uses the approach of coating taxol with albumin to reduce the side effects associated with standard taxol (paclitaxel), making it possible to give it without steroids (which can be a rather bothersome issue for many patients, causing problems from severe insomnia to very high blood sugars and more) and also reduce some other taxol-associated side effects like joint and muscle aches (see prior post on Abraxane for more background information). It’s also possible to give doses that may be high enough to work better than standard taxol.  Abraxane has been approved in breast cancer since 2005, and it’s used here and there in lung cancer, but there is relatively little data about it in lung cancer.  However, earlier this week, it was reported that a large trial of carboplatin/Abraxane vs. carboplatin/taxol for initial treatment of advanced NSCLC was “positive”, at least in terms of showing a significant improvement in response rate.  But what does this mean for the field of lung cancer?

The short answer is that we don’t know because we need much more information, to be presented at the large ASCO meeting in early June,  to really be able to assess the impact that this trial should have.  For starters, response rate isn’t the most important endpoint in lung cancer, and I would consider it to be of relatively little importance compared with overall survival, tolerability/quality of life, and progression-free survival.  Response rates represent the proportion of patients with tumor shrinkage beyond a strict set of criteria, but there are many reasons that the impact of a treatment may be dissociated from response rate.  You’d definitely prefer to see major tumor shrinkage in more patients rather than fewer, but some treatments like the EGFR inhibitor Tarceva (erlotinib) or the investigational ALK inhibitor crizotinib (PF-02341066) may have a relatively or extremely low response rate in a broad population but be hugely effective in that group in which the cancer shrinks.

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Recent Webinar with Dr. Weiss on Potential Use of Post-Operative Tarceva Available

Here’s a podcast from the webinar presentation earlier this month by our beloved Dr. Weiss, covering the open question of whether we should consider giving an EGFR inhibitor like Tarceva (erlotinib) as an adjuvant (post-operative) therapy following potentially curative surgery for early stage NSCLC.  It’s a setting in which there is a good rationale if we extrapolate from the setting of metastatic NSCLC, at least for patients with an EGFR mutation, but we’ve made incorrect presumptions before when we extrapolate.

Dr. Weiss reviews the pros and cons and the scant relevant data in his podcast.  Below you’ll find the audio and video versions of his presentation with Q&A that followed, as well as the figures and transcripts that go with this.

weiss-adjuvant-egfr-tki-webinar-audio-podcast

weiss-adjuvant-egfr-tki-webinar-figures

weiss-adjuvant-egfr-tki-webinar-transcript

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Expert Case Discussion: Treating the Patient with a “Precocious Metastasis” with Curative Intent

Here is the last of three interesting cases I discussed with Drs. Alex Farivar, thoracic surgeon at Swedish Cancer Institute here in Seattle, and Anne Tsao, medical oncologist at MD Anderson Cancer Center in Houston.  This particular case is  a man I saw a few years ago, with a solitary brain lesion and what otherwise appeared to be a very isolated lung cancer in the right upper lobe.  His case brings up issues of the feasibility of treating someone with a solitary lesion with curative intent.

Here is the audio and video versions of the discussion, along with the transcript and figures.

rt-farivar-tsao-case-3-precocious-met-audio-podcast

rt-farivar-tsao-case-3-precocious-met-transcript

rt-farivar-tsao-case-3-precocious-met-figures

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The Predicament of Poorly Differentiated NSCLC/NSCLC NOS

A topic that came up in a recent expert round table case discussion was the issue of how to manage a patient with a lung cancer for which the pathology report says “NSCLC not otherwise specified (NOS)”, or “poorly differentiated NSCLC, NOS”.  What does this actually mean, and what does it mean in terms of treatment options?

Tumors of pretty much all types are categorized by their tumor grade, how “differentiated” they are, which basically means, “how much do the cancer cells look like the cells they started out as?”.  Different cells of the body start out as stem cells, which means that they’re not specialized to be any special kind of cell, like one that detects light in the back of the retina, lines the esophagus, or is optimized for lung function.   Most cells of the body are differentiated, so that the appearance under a microscope shows that it’s a liver cell, part of the kidney filtering mechanism, heart muscle, etc.

Cancer cells, however, have mutations in them that make them grow and divide faster than other cells (that’s why they make a tumor that pushes other tissues aside), and they usually have several.  As they grow and divide, they often make sloppy copies of their DNA that leads to more mutations.  Cancers therefore are made of cells that may look a lot like the normal cells they originated from (well-differentiated), or they have lots of mutations that make the cells look so chaotic that they don’t look at all like the cells they started out as (poorly differentiated).

Today, oncologists want to know whether a non-small cell lung cancer (NSCLC) is an adenocarcinoma, squamous cell carcinoma, large cell neuroendocrine carcinoma, etc.  But about 20% of the time on various studies, we get an answer back of “NSCLC not otherwise specified”.  As explained by Dr. Matt Horton, expert lung cancer pathologist, a lung tumor may be classified as NSCLC  NOS because of either of two reasons:

1) there isn’t enough tissue, because the biopsy material was very scant, or

2) the tumor is so poorly differentiated that even with all of the material in the world, a good pathologist couldn’t identify the underlying NSCLC histology

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Case Discussion with Experts, Drs. Julie Brahmer & Greg Riely, Part 1

Here’s a webinar case discussion I did with Drs. Julie Brahmer from Johns Hopkins in Baltime, and Greg Riely from Memorial Sloan Kettering Cancer Center in New York.  They’re great thoracic oncologists as wellas friends, and they were kind enough to join me for discussion of several complex cases that don’t have clear answers and illustrate the reality that even when we know the evidence, there’s plenty of room for judgment.

Our first case is about a 63 year-old woman who has a poorly differentiated NSCLC that is just outside of the range we’d feel feasible for radiating, and it brings up issues related to trying to integrate chemo and possible radiation, the debatable role of agents like Avastin (bevacizumab) and Alimta (pemetrexed) for cancers that are hard to classify, and then how we approach managing patients who have responded well — observation or maintenance?

Here is the audio and video versions of the podcast, along with the associated transcript and figures.

rt-brahmer-riely-webinar-case-1-audio-podcast

rt-brahmer-riely-webinar-case-1-transcript

rt-brahmer-riely-webinar-case-1-figures

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Podcast of Q&A Portion from Molecular Markers Webinar with Dr. Pennell

   Here’s the podcast of the Q&A portion of the excellent webinar with Dr. Pennell on Molecular Markers in Management of NSCLC. 

dr-pennell-molecular-markers-qa-audio-podcast

dr-pennell-molecular-markers-qa-transcript

dr-pennell-molecular-markers-qa-figures

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Round Table with Drs. Anne Tsao and Alex Farivar, Part 2: Mesothelioma

This is part 2 of my round table case discussion with Dr. Anne Tsao, a medical oncologist and thoracic oncology expert from MD Anderson Cancer Center in Houston, and Dr. Alex Farivar, a thoracic surgeon with expert training in mesothelioma at Swedish Cancer Institute in Seattle. This particular case covers a patient with a mesothelioma, cancer of the lining around the lung, which is also known as malignant pleural mesothelioma.

Here is the audio and video versions of the podcast, along with the transcript and figures.

round-table-with-drs-tsao-and-farivar-part-2-meso-case-audio-podcast

round-table-with-drs-tsao-and-farivar-part-2-meso-case-transcript

round-table-with-drs-tsao-and-farivar-part-2-meso-case-figures

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Watching Small Lung Lesions Do Nothing: “Ground Glass Opacities” Don’t Progress Over Years If They’re Watched, Not Resected

In one of my earliest posts about bronchioloalveolar carcinoma (BAC) (in the dark ages, pre-Twitter), I wrote on the subject of managing small BAC-type lesions, which tend to appear as small hazy areas called “ground glass opacities” (GGOs) and suggested that some of these cancers may be so indolent that they don’t need to be treated, even if they have the word “carcinoma” in the diagnosis.

(a representative GGO identified by arrow)

Now there is a proposal to change BAC to “adenocarcinoma in situ“, a pre-cancerous condition, reflecting the idea that these lesions have such a favorable prognosis that they shouldn’t necessarily be put in the same category as invasive lung cancers (pure BAC is a non-invasive lesion that shouldn’t be able to get into the bloodstream and spread outside of the lungs).  And now, there’s a new article out of Japan that describes the experience of patients with BAC and multiple GGOs, some of which were resected and some not very accessible and some just watched.  It turned out that just watching seemed to be a pretty good strategy.

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Podcast by Dr. Camidge on ALK Rearrangements and a New Era of Molecular Oncology

   Last week, Dr. Ross Camidge from the University of Colorado joined me on a webinar entitled “One Size Does Not Fit All” in which he discussed the early work on ALK rearrangements and the novel agent PF-02341066 (now known as crizotinib) in particular, and the new era of molecularly defined practice of oncology in particular.   This story has been widely considered to be among the most important in the field of lung cancer over the last few years, and Dr. Camidge did not disappoint.

   Not only did many of the participants in the live program write comments here expressing their positive feedback on the great energy and overall quality of the program, but both our transcriber and the editor of our podcasts independently commented to me that they thought it was a terrific podcast and that they learned a lot (and they don’t have a special, vested interest in lung cancer issues).

   Here’s the audio and video podcast links, as well as the transcript and the figures from the webinar:

dr-camidge-on-alk-inhibitors-and-molecular-oncology-audio-podcast

dr-camidge-on-alk-inhibitors-and-molecular-oncology-transcript

dr-camidge-on-alk-inhibitors-and-molecular-oncology-figures

   Finally, I’d like to personalize this a bit, because one of the people who was mentioned in the podcast, Andy Hill, has also been featured in the local news in both Seattle (link to news report here) and Denver (link here) as a remarkable example of the promise of molecular oncology.   He’s also been a dedicated and extremely helpful supporter of GRACE in terms of both financial support and participating in our recent programs and some meetings as we work on the future directions for our organization.  So I’d like to dedicate the program to Andy and hope he continues to redefine the great success of this work in how well he does.

   Speaking of which, we could really benefit from your support for these programs.  This webinar wasn’t from a grant but rather from your contributions.  I hope you find these activities helpful and will support them.  I’d also encourage people to tell others, provide the link, if you know of anyone else who might benefit from learning the material in our educational programs.  We’d hate to think of the Andy Hills out there who may miss a chance for a very helpful treatment because they simply didn’t know such a possibility might exist.  And unfortunately, many oncologists are still not aware of these developments: the field is simply moving too quickly.

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A New Series of March Webinars

That short month of  February makes it so that March really sneaks up on you! We’re just a few days from March and our first of several upcoming webinars I need to tell people about.

The first will actually be on Monday, March 1st (just 4 days from now), with Dr. Jared Weiss from University of Pennsylvania joining me at 8 PM EST/5PM PST for a discussion of two very different but timely topics.  First, Dr. Weiss will cover the controversial and completely open question of what role EGFR inhibitors might play in early stage NSCLC, or whether we should even be talking about and checking for EGFR mutations in patients who don’t have advanced non-small cell lung cancer (NSCLC) (where most of the research and discussion has been concentrated).  Next, I’ll turn to a debate that has been ongoing for decades in lung cancer: should the minority of patients with very localized small cell lung cancer (SCLC) undergo surgery?  A very recent review of results from a large database put this topic back in the lung cancer news.  So should SCLC ever be managed surgically?  I’ll try to highlight the pros and cons.

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