Immune/Vaccine-based therapies
Emerging immunotherapies and cancer-based vaccines in lung cancer
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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
Podcast on Current Questions, Clinical Trials in Adjuvant Therapy for Resected NSCLC
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.
Podcast: Play in new window | Download (38.8MB) | Embed
Lucanix: A Vaccine Being Tested as a “Maintenance” Strategy in Advanced NSCLC
Over the past several weeks, coincident with the opening of a new large clinical trial and some publicity associated with that, several people have asked me here about a lung cancer vaccine called Lucanix (full name belagenpumatucel-L, so a near guarantee that nobody will call this anything but Lucanix). My initial response was that I knew essentially nothing about it and more or less implied that there must not be much to it if there was really no buzz about it within the lung cancer community. But that’s a very simplistic view that goes against one of the issues I feel strongly about, namely that hype isn’t the same as promise. There are enough approaches that I’ve been critical of despite “buzz” (RFA, proton beam radiation, celebrex, just to name a few I’ve minimized over the past few weeks) that it would be completely hypocritical for me to suggest that a lack of attention from the media or lung cancer establishment means that a treatment isn’t worth pursuing. I’ve seen over the years that the interest in a treatment is a combination of the favorable findings from early work, the public relations machine and marketing muscle of the sponsor company, how explainable it is (we like a good “story”, so it’s easier to explain that something blocks EGFR or is antiangiogenic than that something is an aurora kinase inhibitor), and certainly some luck about what just happens to catch on. I’ve also been following some treatments that seem to get little traction despite quite encouraging results (talactoferrin alpha, for instance), probably because they’re products of small companies, and/or have been studied by people who don’t immediately attract media attention.
So it was only fair for me to review the available information about Lucanix and provide a more informed opinion. T0 their credit, folks at NovaRx, the company working on Lucanix, saw my comments announcing my intention to write a more educated piece, and they proactively sent me several files with background information about the company, Lucanix, and the trial being conducted now. After several attempts to connect, I spoke earlier today with Ms. Carissa Schumacher, Director of Corporate Development, and Dr. Habib Fakhrai, President; both were eager to discuss the promise and challenges of the early work with Lucanix and the new trial moving forward. I’ve never had the leadership of a company provide more enthusiastic and open communication, so kudos to them for that.
EGFR Vaccine Early Results Published
The epidermal growth factor receptor (EGFR) is a central component of a cell pathway for growth and cell division that is thought to be affected in many cancers, including NSCLC. EGFR inhibitors have been the focus of clinical trials for several years and are now used for many types of cancer. Nearly all of this work has focused on either oral tyrosine kinase inhibitors that inhibit the back end activity of the receptor inside the cell or monoclonal antibodies that block the extracellular front end of the receptor that binds to the ligand (the matching protein that attaches to the receptor) that is supposed to trigger the receptor. But a new study was just published in the Journal of Clinical Oncology that describes the early experience of studying a new vaccine against EGFR in the treatment of advanced NSCLC (abstract here).
This study came out of Cuba (investigators not known to me) and used a vaccine made of one of the proteins that serves as a ligand for EGFR, attached to a carrier protein. This vaccine is given with an adjuvant, which in this case doesn’t mean post-operative treatment, but rather refers to a treatment that is given with a vaccine to help stimulate the immune system to generate a robust immune response.
A total of 80 patients with advanced NSCLC who had completed first line platinum-based chemo (4-6 cycles) at least 28 days earlier were then randomized (1:1, so evenly divided) between the active vaccine approach and “supportive care”, or general follow-up and treatment of any specific symptoms a patient developed. The patients who received the actual treatment received a low dose of cyclophosphamide, a chemotherapy that in this setting was used as an immunostimulant/adjuvant, 3 days before the vaccine, and then the vaccine injection on days 1, 7, 14, 28, and then monthly after that. Continue reading
MAGE-A3 as a Vaccine Target in NSCLC
One of the more intriguing presentations at ASCO this year was the one in which a novel vaccine against a protein called MAGE-A3 was tested in patients who underwent surgery and then received the vaccine post-operatively. What is MAGE-A3? It’s a nearly tumor-specific antigen, which means that it’s a protein seen almost exclusively on cancer cells, including lung cancer, head & neck, bladder, and melanomas. The only normal non-cancer tumor tissue it’s seen on in the testicles, but there have been no problems with auto-immune or other complications against testicular tissue, as these cells don’t have the capacity to generate an immune response.
The limited available evidence suggests that expression of MAGE-A3 is associated with a worse prognosis, and along with that is the finding that it’s more commonly seen in higher cancer stages. It’s seen in only about 16% of stage IA NSCLC tumors, about 35% of stage II and IIIA resected NSCLC tumors, and about 50% of more advanced NSCLC cancers. Continue reading
Stimuvax Vaccine Approach in NSCLC: Renewed Hope for Immunotherapy
Immune-based approaches in lung cancer tend to generate significant buzz among patients and the general public, as well as in the media, but not as much optimism within the oncology world. Much of that is for good reason: while the concept of a minimally toxic, long-lasting anti-cancer approach like a vaccine is very appealing to all of us, oncologists have seen many hyped immune-based therapies deliver far less than their promise. This is for several reasons. One is that cancer cells derive from normal host cells, so it can be hard to find targets on a cancer cell that aren’t also seen on normal cells. If the immunologic treatment fights normal tissues as well, it can lead to autoimmune complications. Also, many of the early studies measure success as an immune response measured on skin or in a test tube, not the more meaningful endpoints that we really care about, like tumors shrinking or people living longer. Who cares if your blood cells seem to recognize the target in a lab test, if it doesn’t translate to a patient actually doing better because of that? Also, the idea of a vaccine is generally employed before someone has the disease: you get vaccinated not when you have measles, but before you get it, so your immune system can mount a response at the first minimal threat of it. We think of immune-based therapies being most effective against a minimal tumor burden, which is not something we see enough in lung cancer, especially advanced disease. Finally, chemotherapy as well as progressing cancer can leave the body relatively immunosuppressed, so that the immune system may not have the ability to mount a strong enough response to combat a cancer meaningfully. At the end of the day, we don’t have vaccine therapies for active cancers yet. But as I write this, I wonder when I’ll need to go back to revise that statement. The FDA is considering a vaccine for advanced prostate cancer, and there are a few good leads in lung cancer as well. Today I’ll focus on L-BLP 25, now also known as Stimuvax® Continue reading
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