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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
It’s ASCO Season: Join Us to Discuss Lung Cancer Highlights on June 28th
We’re heading into the season where much of the biggest news in the cancer world for the year is about to be released, in press releases and full presentations at our annual conference of the American Society for Clinical Oncology (ASCO). The meeting is June 1-5, in Chicago, and I’ll be presenting some of my own work and chairing an educational session on the changing relationships between patients and doctors from the growing knowledge base of patients from online sources. There will be several other presentations that may well have implications that can change how we practice and offer new treatment options.
Dr. Joel Neal
Dr. Mark Socinski
On June 28th, at 7 PM Eastern/4 PM Pacific, we’re going to have two terrific guest faculty members leading us through the most interesting and important work: Dr. Joel Neal, Assistant Professor in Medical Oncology at Stanford, and Dr. Mark Socinski, Professor and Director of the Lung Cancer Program at the University of Pittsburgh. Rather than divide by cancer type, we’ll see what the most relevant ASCO presentations are and then divide them between our two great speakers. Each will speak for about 30 minutes, followed by time for a question and answer session with our live audience.
Registration is free: all you need to do to join our ASCO Lung Cancer Highlight webinar is to sign up through this link. We’ll be editing the content of the program to make it available in free podcasts, but you’ll want to be there for the live event!
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.
Dr. Alice Shaw on Clinical Factors Associated with Molecular Markers
I’m happy to bring you now the second part of the Santa Monica webinar, developed with the LUNGevity Foundation, on “Molecular Markers in Advanced NSCLC: Who to Test and What to Test For?“, in which I was joined by Drs. Charles Rudin (Johns Hopkins University in Balimore, MD), Alice Shaw (Massachusetts General Hospital in Boston, MA), David Spigel (Sarah Cannon Cancer Center in Nashville, TN), and Glen Gloss (University of Ottawa in Ontario, Canada).
In this short podcast, Dr. Alice Shaw reviewed the frequencies of different molecular markers in advanced NSCLC as a function of patient sex, smoking status, race, and tumor histology. This work is very interesting, of course, because if we only do molecular marker studies of people with an adenocarcinoma or never-smokers, we not only won’t ever find potentially relevant mutations in people with other histologies and those with a smoking history, but we won’t have any good idea of the probabilities of finding them either.
Here is the podcast in audio and video formats, as well as the transcript and figures.
Molecular Markers SM Pt 2 Shaw on Markers by Clin Factors Audio Podcast
Molecular Markers SM Pt 2 Shaw on Markers by Clin Factors Transcript
Molecular Markers SM Pt 2 Shaw on Markers by Clin Factors Figs
Podcast: Play in new window | Download (Duration: 10:48 — 24.9MB) | Embed
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
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.
How does the diagnosis of BAC shape systemic therapy considerations today?
It’s not uncommon for a question here to be about the a pathologist’s terminology on a report that equivocates about whether a lesion is bronchioloalveolar carcinoma (BAC) or another form of adenocarcinoma, perhaps “well-differentiated adenocarcinoma”, especially if it has a radiographic appearance of a hazy infiltrate or many small ground glass opacities. Meanwhile, there’s a new classification of lung cancer subtypes that obliterates the term BAC, instead favoring a definition of adenocarcinoma in situ, classifying small non-invasive lesions previously called BAC as a pre-malignant condition. How have the changes over the past few years changed how we should approach BAC?
I would have to say that the new reassignment of BAC as adenocarcinoma in situ hasn’t taken the lung cancer world by storm and that I still think of the clinical entity as BAC. For the preceding decade, the definition the pathologist’s used technically excluded a lesion with even 1% or 5% of the lesion being invasive as being called BAC, even if it acted for all the world like BAC. Clinicians learned not to be too hung up on a pathologist’s technical definitions and tended to define BAC more functionally/operationally. General oncologists and expert lung cancer specialists alike managed BAC based on the overall picture of how it behaved if it looked like a BAC pattern.
Talactoferrin: Where are we now and what can we expect?
Thank you fortmyr for bringing our attention to the recent publication of exciting data on talactoferrin. We’ve talked about talactoferrin before on GRACE. This is an exciting new drug that both Dr. West and I feel has a lot of promise.
When you eat food, you ingest a lot of bacteria with your food and so it’s not surprising that there are a lot of immune cells in the gut. Appropriately this system is called GALT, or gut-associated lymphoid tissue. In the simplest terms, talactoferrin is a chemical that activates GALT in the hopes that this will activate the immune system to better fight the cancer. The drug is not absorbed and does not travel in the bloodstream the way that chemotherapy and even most targeted agents do. Rather, we believe that it activates GALT, and then the body’s own immune cells go off to better fight the cancer. Dr. West has described the proposed mechanism of action in much greater detail, and I refer the curious to his post. Talactoferrin is found in several body fluids. Poetically, its concentration is highest in breast milk, where it is believed to support development of the infant’s immune system, thus the term, “mother’s milk.” Cycles are fourteen days in length. For twelve weeks, the patient takes this pill twice per day, and then there are two weeks off before starting the next cycle.
Two major studies started the clinical work on talactoferrin. One randomized patients to who were previously treated with chemo to talactoferrin or placebo. Dr. West has reported on these results in 2008. All patients were previously treated with at least one and up to two lines of chemotherapy. In other words, these were 2nd line or 3rd line patients. In the US, I would not have opened this study for my patients because of the randomization to placebo. Since alimta, docetaxel and erlotinib all have proven efficacy in the second line, I would have felt ethically uncomfortable. As a rule, I believe that investigators should only open trials that they believe are very promising compared to the standard of care and that they would feel comfortable putting themself or a loved-one on if they had cancer. In fairness, the trial was conducted in India. The little that I know about lung cancer care in India is only from GRACE members’ postings. If 2nd line chemotherapy is not universally available in India, making placebo equivalent to the standard of care, then this trial would seem more acceptable to me. Regardless, the comparison to placebo does provide quality information about the efficacy of talactoferrin.
This was a randomized phase II study. This means that like any phase II study the goal was not to definitively prove the efficacy of talactoferrin, but rather to see if the agent was worthy of further evaluation in a larger phase III study. This design has gained favor because without a control arm, single-arm studies can be made to look very promising just by using strict inclusion criteria. This problem has resulted in too many patients being enrolled on phase III studies that were ultimately proven not to help. Just to be clear what I’m talking about, I’ll make up an example. If I designed an uncontrolled (single-arm) phase II study of dark chocolate for 2nd line treatment of lung cancer and wanted to artificially make it positive, I could require all patients to have PS0, ideal renal function, absolutely normal bone marrow function, minimal burdens of cancer and to have had dramatic response to their first line of chemotherapy. Even if dark chocolate did nothing to stop cancer growth, these patients would live longer than historic controls, leading to a “positive” study. We would then proceed to phase III study, where dark chocolate would get trounced by a standard second line agent, because it is not actually active and patients on both arms would have the same requirements to enter the study. Of course, the major confounder here would be the massive improvement in quality of life that comes with dark chocolate.
Preliminary Results from the AVAPERL Study: The Alimta/Avastin Combo in Maintenance Looks Favorable
I’m at Swedish Hospital, not in Stockholm, Sweden now, where the European Multidisciplinary Cancer Congress is going on. But there, the preliminary results of the AVAPERL phase III randomized trial were just reported, and they certainly look encouraging for the combination of Alimta (pemetrexed) and Avastin (bevacizumab) as a maintenance therapy for patients with Avastin-eligible advanced NSCLC who hadn’t progressed after four cycles of cisplatin/Alimta/Avastin, compared with maintenance Avastin alone.
(click on image to enlarge)
As I mentioned, I don’t have all of the details from the presentation, really just the press release, which at least conveys some highlights. As shown above, a total of 362 patients who hadn’t progressed after first line chemo/Avastin were randomized to either of the two maintenance therapy arms, and the combination arm showed a significantly longer progression-free survival (PFS) counting from the beginning of all treatment, at 10.2 vs. 6.6 months (HR 0.50, p < 0.001), but also a numeric result for PFS that far exceeded the numbers we’ve seen from other first line trials, where PFS has generally been in the 5-7 month range. There were no unexpected safety issues, but otherwise, I don’t have other details.
Stage IV Non small cell Lung Cancer in the Elderly: Review of Data and update on the Published results of the French IFCT-0501 (Quoix) trial
Introduction
When I wrote my first review article on the treatment of the elderly, I entitled it, “NSCLC in the elderly—the legacy of therapeutic neglect.” Dr. Corey Langer and I chose the title to directly criticize the major mistake that we perceive in the treatment of the fit elderly—a therapeutic nihilism that leads oncologists to not give sufficiently aggressive treatment to the fit elderly. Lung cancer is a terrible cancer and failure to suppress it with sufficiently active therapy leads to great suffering. This is as true in the older patient as in the younger patient. However, there is great misunderstanding about the efficacy of therapy in the fit elderly patient, the subject of this post. I will seek to summarize coverage of this topic on GRACE previously, highlighting the now published French data on 1st line treatment of the elderly. You may have noted the repeated use of the word, “fit.” Not all elderly patients are as fit as younger patients—aging brings with it more medical problems and more pills; not all elderly patients are as fit as younger patients with lung cancer. I will address this topic in a follow up post dedicated to this important topic.
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