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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
Low Testosterone with XALKORI (Crizotinib): A Newly Identified Side Effect
It started with a patient reporting an unexpected side effect. A 35 year old ALK-positive man with lung cancer who was on XALKORI (crizotinib) noted that he had markedly diminished libido lower energy that had been worsening while on treatment, despite the fact that his cancer appeared to be responding well His doctor checked his testosterone (T) level and noted it was well below the normal range, then referred him to the endocrinology clinic for consideration of testosterone replacement therapy, which he decided to do, and which helped with his symptoms. Because this occurred at the University of Colorado, where they have more experience with patients on XALKORI than almost any other institution, they checked testosterone levels of as many men as they could find on XALKORI and compared the results to a comparable group of men with lung cancer who were not on XALKORI.
Low T levels lead to fatigue and depression, hot flashes and night sweats, potentially insomnia, as well as diminished sexual interest and function. Low testosterone (sometimes called hypogonadism) is relatively common in cancer patients overall, though it historically hasn’t been well studied. It’s generally unclear whether low T is caused by the underlying disease, the treatment, other medical issues, or some combination of these factors.
The initial observation from the patient at the University of Colorado led to the report that was just published online in the journal Cancer, showing that 100% of their male patients on XALKORI had a T level below normal (range 241-850 ng/dL there, though this varies a bit from lab to lab), compared with just 6 of 19 matched control patients with a similar distribution of age and other factors, median T levels 131 vs. 311 ng/dL. Also very interestingly, a few patients who stopped and started XALKORI due to other side effects and had their T levels checked at a few time points along the way, showing a remarkably good correlation between T levels falling quickly when on XALKORI, rising within days on a break from it, then dropping again when the drug is restarted:
The authors developed a new policy of checking testosterone routinely in their male patients and referring those with low testosterone to their colleagues for consideration of T replacement therapy that could potentially help reverse both sexual side effects and the fatigue and depression. However, since T can also potentially lead to worse problems with urinary function in men with an enlarged prostate and may accelerate prostate cancer in a man who has that, the overall conclusion is that the decision to start T replacement is an individualized one that depends on the degree of symptoms that a patient has and the anticipated risks and benefits of the treatment.
Radiation to Address Cells with Resistance to Targeted Therapies
Introduction
Thank you to member Craig for asking some excellent questions in response to my Highlights of 2011 webinar (http://cancergrace.org/lung/2012/03/30/qa-lc-highlights-weiss/#comment-9498 ). Thank you also to Dr. West, who emailed me to comment more on the idea of radiation for cells with acquired resistance.
We’ve spoken at length about EGFR and related mutations such as EML4/ALK and ROS1 on GRACE. For those who are not familiar with these subjects, I will refer you to my webinar for a summary on the most recent data on EGFR, EML4/ALK and ROS1:
(Parenthetically, we did also cover CT screening and optimal management of elderly patients at http://cancergrace.org/lung/2012/03/22/dr-weisss-highlights-in-lung-cancer-2011-ct-screening-optimal-management-of-elderly-patients-with-advanced-nsclc/ )
In the Q&A for this webinar that covered some of the existing approaches to resistance, Dr. West pushed me and asked if there was one that was particularly promising. Well, I’ve spent a ton of time thinking about this problem and have written a trial to attempt to address it. I couldn’t resist the bait and mentioned my trial. In this post, I’d like to review the rationale for the approach that I described and address Craig (and Dr. West’s) question about how appropriate this approach will be to new mutations, such as EML4/ALK and ROS1.
The Approach:
(click on image to enlarge)
The basic idea is to take patient whose cancer has grown on tarceva, do cyberknife to the spots that have grown to eliminate the resistant clones, then continue using tarceva for the rest of the cancer that has shown evidence for ongoing sensitivity to tarceva.
Question and Answer Session with Dr. Weiss on Lung Cancer Highlights, 2011
Here’s the final piece of the webinar with our own Dr. Jared Weiss on Highlights in Lung Cancer from 2011 — the question and answer session that followed his presentation. Below is the transcript, figures, and the audio and video versions of the podcast.
Dr. Weiss Lung Cancer Highlights 2011 Q and A Transcript
Dr. Weiss Lung Cancer Highlights 2011 Q and A Session Figs
Dr. Weiss Lung Cancer Highlights 2011 Q and A Session Audio Podcast
Podcast: Play in new window | Download (Duration: 18:14 — 40.0MB) | Embed
Refining CT based lung cancer screening with a blood test?
Many people in the lung cancer world consider the National Lung Screening Trial (NLST) that demonstrated a 20% improvement in survival from CT-screening higher risk people for lung cancer as a major advance in the field, befitting coverage in Dr. Weiss’s summary of lung cancer highlights from 2011, but this hasn’t yet led to wholesale adoption of the practice. Why not? Some people say that it’s just one study and that we need more evidence, but it’s hard not to believe that implications for health care resource utilization (i.e., cost and practical implementation) aren’t a big part of the challenge. Annual CT scans will/would add a lot of cost when applied for the millions of people just in the US who would be appropriate candidates by the definition of the study (age 55-75 and with a 30 pack-year smoking history). In addition, we know that CT screening detects a lot of nodules that require plenty of follow-up scans and cause significant anxiety but ultimately prove to not be cancer. What if we could add another factor that could raise or lower our suspicion and potentially enable us to modify the frequency of scanning and/or our enthusiasm for escalating the workup?
I’ve covered one such approach in a prior post describing a test analyzing chemical compounds in the exhaled breath of patients, and this research is ongoing. But another strategy is to analyze the blood of patients in search of preliminary evidence of cancer that might be detectable at the time of or even before the earliest imaging findings suggestive of cancer. The EarlyCDT-Lung test is designed to do this by looking for immuno-biomarkers (“auto-antibodies” created by the body in reaction to a protein detected within), any of a panel of 6-7 that could signify early cancer if one or more of these is elevated.
Selective Androgen Receptor Modulator GTx-024: A New Effective Treatment for Cancer Cachexia?
Anorexia-cachexia syndrome (ACS), a negative spiral of diminished appetite and weight loss (lean body mass), is a common problem in many kinds of cancer, where it not only leads to patient weakness and diminished function but is also associated with shorter survival. While it’s possible that the ACS is a late effect that might be an irreversible product of progression of an underlying cancer, it may also be that ACS directly contributes to a patient’s decline by making them unable to tolerate further cancer therapy.
GTx-024, also now known as Ostarine™ or enobosarm, is a selective androgen receptor modulator (SARM), which activates the androgen (male hormone) receptor and leads to the activation of a wide range of genes in the cell, the net result of which being increased muscle mass, increased bone mass, and often an increase in mood, energy level, sense of well being, and libido. Not surprisingly, these are the exact opposite effects we routinely see in men placed on androgen suppression as a common (and effective) treatment for prostate cancer. Risks include increased hair growth/virilization in women, prostate stimulation and hyperplasia (excess growth) in men, elevated red blood cell counts (potentially to levels above normal), decrease in HDL cholesterol (the “good cholesterol” associated with exercise and decreased risk of cardiac events), and potentially abnormalities in liver function tests.
The phase I and II studies in patients with cancer-associated weight loss thus far have pretty consistently shown that treatment with daily oral GTx-024 leads to a modest (typically 1-2 kg) increase in lean body mass after 16 weeks, while recipients of placebo had no change or a trend toward slight further weight loss. The GTx-024 studies also assessed physical function with a stair climb function, assessing both the time required to ascend stairs and “power”. The pattern is the same as with body mass: there is a modest but statistically significant improvement in stair climb function in recipients of GTx-024, but little or no change in recipients of placebo. Here are some figures that represent the results in the subset of patients with NSCLC, for instance:
In addition, improvement in function on the stair climb exercise was also associated with an improvement in quality of life on an “anorexia-cachexia scale” (so the questions were specifically related to eating and weight issues, not more global qualify of life). More importantly, one subset analysis of this work also suggested that a worse survival associated with weight loss could be abrogated with the addition of GTx-024.
Dr. Weiss’s “Highlights in Lung Cancer, 2011″: CT Screening & Optimal Management of Elderly Patients with Advanced NSCLC
This is the third and final part of Dr. Weiss’s presentation on “Highlights in Lung Cancer, 2011″. After focusing on developments in relatively narrow subpopulations with distinct molecular markers in the first two parts of his webinar, Dr. Weiss closed with his coverage of a couple of issues with broader applicability: the new data supporting CT screening for higher risk people with a significant smoking history, and also some new data addressing the question of whether elderly patients are best served by receiving single agent or doublet chemotherapy.
Below you’ll find the podcast of the program in audio and video formats, as well as the transcript and figures for this activity.
Dr. Weiss Highlights in Lung Cancer 2011, Pt. 3 CT Screening and LC in Elderly Audio Podcast
Dr. Weiss Highlights in Lung Cancer 2011, Pt. 3 CT Screening and LC in Elderly Transcript
Dr Weiss Highlights in Lung Cancer 2011, Pt. 3 CT Screening and LC in Elderly Figs
Podcast: Play in new window | Download (Duration: 13:57 — 40.8MB) | Embed
Lung Cancer Highlights, 2011 by Dr. Weiss, Part 2: ALK and other New Molecular Targets
Here is the second part of the presentation on “Lung Cancer Highlights, 2011″ by Dr. Jared Weiss. This section of his talk focuses on the striking story of the identification of the ALK rearrangement as a relevant target in lung cancer, along with an impressive treatment for this subgroup, and other new targets, such as ROS-1.
Below you’ll find the audio and video versions of the podcast, as well as the transcript and figures.
Dr. Weiss Lung Cancer Highlights 2011, Pt 2 ALK and New Molecular Targets Audio Podcast
Dr. Weiss Lung Cancer Highlights 2011, Pt 2 ALK and New Molecular Targets Transcript
Dr. Weiss Lung Cancer Highlights 2011 Pt 2 ALK and New Molecular Targets Figs
Podcast: Play in new window | Download (Duration: 8:21 — 24.8MB) | Embed
2011 Highlights in Lung Cancer, by Dr. Jared Weiss, Part 1: The EGFR Axis
Apologies for the long wait since our own Dr. Weiss’s upbeat and thoughtful review of the leading stories about lung cancer in 2011. Dr. Weiss covered a lot of ground in his presentation that was followed by a Q&A session, so we’ve broken that up into several short pieces that cover a few highlights at a time. In fact, we’re going to make an effort to have podcasts shorter and easier to digest in the future.
The first part is on EGFR-based therapies, including the EURTAC trial of the EGFR tyrosine kinase inhibitor (TKI) Tarceva (erlotinib) vs. standard doublet chemo in a European, EGFR mutation-positive patient population, followed by work on EGFR TKI/monoclonal antibody combinations: one being the single arm afatinib/Erbitux (cetuximab) for patients with acquired resistance after a good response to earlier EGFR TKI therapy, and the second being Tarceva with either the c-MET antibody MET-MAb or placebo.
Here’s the audio and video versions of the podcast, along with the transcript and figures for this portion of the program.
Dr. Weiss Lung Cancer Highlights 2011 Pt 1 EGFR Axis Audio Podcast
Dr. Weiss Lung Cancer Highlights 2011 Pt 1 EGFR Axis Transcript
Dr. Weiss Lung Cancer Highlights 2011 Pt 1 EGFR Axis Figs
Podcast: Play in new window | Download (Duration: 11:13 — 39.1MB) | Embed
Tips and Tools on Smoking Cessation, by Dr. Mark Millard
This long-overdue podcast by Dr. Mark Millard, Medical Director of the Baylor Martha Foster Lung Care Center and Professor of Pulmonology at Baylor University in Dallas, TX, focuses on many aspects of smoking cessation: how physicians can effectively discuss it with patients, how anyone can discuss the issue constructively with a smoker, and how someone motivated to quit can use a wide range of tools — both behavioral and medical — to optimize their chance of quitting for good.
Here are the audio and video versions of the podcast, along with the transcript and figures for the program.
Dr. Millard Tips and Tools for Smoking Cessation Audio Podcast
Dr. Millard Tips and Tools for Smoking Cessation Transcript
Dr. Millard Tips and Tools for Smoking Cessation Figures
Podcast: Play in new window | Download (Duration: 27:50 — 69.3MB) | Embed
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