January 18, 2013
Lung Cancer Action Network (LungCAN®) applauds the news that President Obama signed into law the Recalcitrant Cancer Research Act last week and offers a huge thank you to PanCan for initiating this effort.
FOR IMMEDIATE RELEASE
PRLog (Press Release) – Jan. 9, 2013 – Lung Cancer Action Network (LungCAN®) applauds the news that President Obama signed into law the Recalcitrant Cancer Research Act last week! This is the first legislation where comprehensive plans for research in cancers with high mortality rates are made a priority and it was only made possible by a true collaborative effort.
A huge THANK YOU goes out to the Pancreatic Cancer Action Network (PanCan) for initiating this effort and who did a great deal of work on this bill. Initially this bill was proposed by PanCan to just cover pancreatic cancer which has a survival rate of six percent (6%). Lung Cancer Alliance’s Lung Cancer Mortality Reduction Act which just addressed lung cancer and was initiated many years ago was in the same position of singling out just one cancer.
Organizations that represented other recalcitrant cancers (cancers that have a very low survival rate) came together and proposed that the National Cancer Institute (NCI) would be required to identify two or more cancers that meet the established criteria — a 5 year survival rate of less than 20% and a death rate of at least 30,000, which is what allowed lung cancer to be included and prioritized with pancreatic cancer in this bill.
It is because of this true collaborative effort that the lung, pancreatic and other recalcitrant cancer communities are celebrating today. The collaboration and compromise, countless hours put in by many, and the persistence by all involved is what gave this bill the momentum it needed to become law.
The landmark legislation requires NCI to examine its current research efforts on cancers with very low survival rates, giving lung cancer and pancreatic cancer a priority. NCI will work to develop scientific frameworks that support progress in the prevention, detection, diagnosis, and treatment of these deadly cancers. At any time, NCI may identify other recalcitrant cancers, defined as cancers with survival rates of below 50%, in which to conduct a scientific framework.
This is a huge milestone for the lung cancer and pancreatic cancer communities as well as other recalcitrant cancer communities and a testament to how powerful collaboration can be in the world of cancer.
We’d like to thank PanCan for all of their efforts in making this a reality.
Sincerely the members of LungCAN®,
American Lung Association
Bonnie J. Addario Lung Cancer Foundation
Cancer Support Community
Cancer Survivors Against Radon
Caring Ambassadors Lung Cancer Program
The CHEST Foundation
Dusty Joy Foundation
Gianni Ferrarotti Lung Cancer Foundation
Lung Cancer Alliance
Lung Cancer Circle of Hope
Lung Cancer Foundation of America
National Lung Cancer Partnership
Respiratory Health Association
Rexanna’s Foundation for Fighting Lung Cancer
Uniting Against Lung Cancer
Upstage Lung Cancer
For more information on the Lung Cancer Action Network visit: http://www.LungCAN.org or Find us on Facebook at http://fb.com/LungCANorg
October 25, 2012
The approach to diagnosing and treating advanced non-small cell lung cancer (NSCLC) has changed significantly over the past few years with the introduction of biomarker testing of tumors. While strides are being made to generate greater awareness of this diagnostic component, all too often patients with advanced NSCLC do not receive tumor biomarker testing during their diagnosis or treatment plan.
Lung Cancer Foundation of America in partnership with Pfizer, would like to gain greater insight about awareness of and experience with tumor biomarker testing at the patient / caregiver level. To accomplish this, we would like to request your participation in a brief survey of approximately 20 questions. Your involvement will help us to better understand the key issues associated with biomarker testing and to develop resources to help those impacted by lung cancer. To access the survey please use the following links to take part.
If you are an NSCLC patient: http://survey.alphadetail.com/wix/p2313123070.aspx?group=LCFA
If you are a caregiver for an NSCLC patient: http://survey.alphadetail.com/wix/p2315748105.aspx?group=LCFA
We appreciate your support and look forward to your input on this important topic within lung cancer. If you have already taken part in this survey simply disregard this message and thank you for your input.
October 1, 2012
The oncology community continues to see major advances in successful application of targeted therapies in the clinic. We are going from a world where we have only a handful of molecular tests and drugs to a world where we are going to have dozens and dozens of molecular tests and therapeutics that will enable oncologists to more effectively treat patients based on the unique molecular drivers of an individual’s tumor.
This report summarizes trends in molecular oncology presented at the ASCO 2012 Annual Meeting and highlights developments that will impact clinical practice. Please visit this link to read the ASCO summary:
September 27, 2012
The Herald Online, WASHINGTON, D.C.
Today, Lung Cancer Alliance (LCA) hailed a major legislative victory in the House of Representatives with the passage of legislation to create a new federal research initiative within the National Cancer Institute (NCI) that would target the most lethal cancers and give lung cancer priority status.
The Recalcitrant Cancer Research Act of 2012 is a modified version of the bill formerly known as the Pancreatic Cancer Research & Education Act which passed the House of Representatives with strong bi-partisan support.
The legislation requires NCI to develop comprehensive plans of research action, or scientific frameworks, to address the most lethal cancers – those with a five year survival rate of less than 50 percent. Immediate attention is to be given to lung and pancreatic cancers.
LCA worked closely with the Pancreatic Cancer Action Network to secure priority status for lung and pancreatic cancers in the legislation which together cause one in every three cancer deaths and whose 5-year survival rates of 15% and 6% respectively have barely moved since the 1972 launch of the “War on Cancer”.
Laurie Fenton Ambrose, LCA President & CEO, credited the achievement to the unrelenting work of the Pancreatic Cancer Action Network and its advocates along with the extraordinary efforts of lung cancer advocates all across the country who worked tirelessly to shine a brighter light on these deadly cancers. Including lung cancer as part of the Recalcitrant Cancer Research Act accomplishes an LCA core priority of bringing a more coordinated and comprehensive research approach to all aspects of the disease.
“These were the driving factors that gave LCA the leverage needed to secure priority status for lung cancer in the compromise bill that was negotiated in the House and Senate Health committees over the past three weeks”, she said. “Thank you advocates and thank you Congressional leaders for helping us realize this long sought goal.”
House leaders for the Recalcitrant Cancer Research Act included Congresswoman Anna Eshoo and Congressman Leonard Lance. In addition, Congresswoman Donna Christensen and Congressman Frank LoBiondo were strong advocates for the bill and House sponsors of the Lung Cancer Mortality Reduction Act.
The Recalcitrant Cancer Research Act of 2012 requires NCI, within 18 months, to carry out a complete inventory of all research done to date, overlooked areas, the availability of researchers, the impact on public health, and then develop a scientific framework for a comprehensive plan of research action to address all aspects of the cancer, including prevention, diagnosis and treatment.
Within 30 days of its development, the scientific framework must be sent to Congress and made publicly available.
“We are hopeful that this new research standing at NCI will bring long needed focus on these lethal cancers, continue to engage advocates in the process, and lead to greater and faster breakthroughs and improvements in survival,” continued Fenton Ambrose. “From prevention, to screening for those without known risk factors as well as those at high risk, to better treatments and even cures—this is what our movement is all about.”
In 2007, LCA secured passage of bipartisan resolutions in both Houses of Congress calling for lung cancer to be a national public health priority.
The Lung Cancer Mortality Reduction Act, legislation calling for a unique multi-agency comprehensive plan of action to reduce mortality by 50% by 2020, was subsequently introduced in both Houses, again with bi-partisan support, and at latest count co-sponsored in the House and Senate by 117 Members.
In addition, LCA joined forces over four years ago with the Pancreatic Cancer Action Network and other lethal cancer advocacy organizations to petition NCI to develop a new targeted research initiative focused on lethal cancers with low survival rates and little progress.
The Recalcitrant Research Cancer Act of 2012 is an amalgam of these strategic efforts.
The Senate is expected to act on the legislation tomorrow and if approved, be sent to the President for his signature.
Lung Cancer Alliance (LCA), www.lungcanceralliance.org, is committed to ending injustice and saving lives through an alliance of advocacy, education, and support. LCA provides live, professional support, referral and information services for patients, their loved ones and those at risk for lung cancer; advocates for multiple millions in public health dollars for lung cancer research; and conducts national awareness campaigns.
September 19, 2012
By John Brinsley
Appeared in BioNews 673
A trio of genetic studies published this week greatly expands researchers understanding of lung cancer.
The studies, published in the journals Cell and Nature, identify new mutations underlying common forms of lung cancer, as well as revealing marked differences in the cancers of patients with and without a history of smoking. It is hoped that the research will provide information for better targeted therapies aimed at treating patients’ specific tumour types.
Worldwide, an estimated 1.6 million people are diagnosed with lung cancer each year. The disease has a relatively low five-year survival rate of between 16 and 20 percent and remains one of the world’s leading causes of death. While smoking is the primary risk factor, a large proportion of patients who contract the disease have no history of tobacco use.
Professor Ramaswamy Govindan, of Washington University School of Medicine in St Louis, USA, who worked on two of the studies, said that the research gives scientists ‘a penthouse panoramic view’ of lung cancer, whereas before they had been only ‘looking through a keyhole’.
The papers – the first in an expected wave of ‘cataloguing studies’ – reveal a complex series of genetic changes across the genome, and identify lung cancer as a highly diverse or ‘heterogenous’ disease. New mutations discovered include those that allow tumours unrestricted growth, or that enable them to evade the body’s immune responses. Other mutations have been unearthed in genes involved in DNA repair mechanisms.
As well as revealing new categories of mutations the studies pinpoint marked genetic differences between the tumours of smoking and non-smoking patients. Professor Govindan describes the genomes of smokers as being ‘battle-scarred by carcinogen exposure’, with mutation rates up to ten times higher than observed in non-smokers, contributing to a much-increased number of mutations.
The studies may inspire better-targeted therapies for lung cancer, as well as refining the approach to clinical trials. Focusing on more specific tumour types means that clinical studies can be smaller, with a greater proportion of participants expected to benefit from treatment. ‘When you look for more effective therapies, you don’t need larger trials’, Professor Govindan explains.
Encouragingly, a number of the mutations identified can be targeted with drugs that are either already licensed or are currently in development for other diseases. Non-smokers in particular were found to be more likely to exhibit mutations in genes such as EGFR and ALK, which can already be targeted by available drugs.
‘We found that almost 75 percent of the patients’ cancers have mutations that can be targeted with existing drugs – drugs that are available commercially or for clinical trials’, Professor Govindan confirms.
However, such news comes with a caveat. Tumours can rapidly become resistant to targeted therapies, with repeat genomic analysis being required in order to select the most appropriate substitutes.
SOURCES & REFERENCES
2 studies could lead to new personalized therapies for lung cancer patients
EurekAlert! (press release) | 13 September 2012
Comprehensive genomic characterization of squamous cell lung cancers
Nature | 09 September 2012
Genomic Landscape of Non-Small Cell Lung Cancer in Smokers and Never-Smokers
Cell | 14 September 2012
Large lung cancer study shows potential for more targeted therapies
EurekAlert! (press release) | 09 September 2012
Lung Cancer Genomic Mapping Yields New Targets, Researchers Say
Bloomberg | 10 September 2012
Mapping the Hallmarks of Lung Adenocarcinoma with Massively Parallel Sequencing
Cell | 14 September 2012
New studies could boost lung cancer survival
OnMedica | 14 September 2012
Studies offer ‘panoramic view’ of lung cancer
Nature News | 13 September 2012
September 12, 2012
Budget officials count the National Institutes of Health as a $31 billion cost, but they don’t count the net benefit.
By MICHAEL MILKEN
Wall St. Journal, Sept. 6, 2012
Not many years ago, the parents of a child diagnosed with leukemia would likely be told to make the most of their short time together. The interval from playground to cemetery was as little as 90 days. Today, thanks to advanced therapies, those parents might be told to start saving for college.
Put aside for a moment the priceless gift that survival is to the family. Consider only the cold economic fact that the child will grow up and contribute to the national economy in myriad ways through decades of employment. Not a bad return on the investment in basic science that made lifesaving drugs for leukemia and many other diseases possible.
Friday morning in Washington, a town not known these days for widespread consensus, a remarkable gathering of leaders begins a weekend of events devoted to a single proposition: Science matters. The senior leadership of the U.S. Senate and House (from both parties) is joining more than 1,000 scientists, medical researchers, university presidents, Nobel laureates, corporate CEOs, cabinet secretaries, philanthropists, presidential advisers and patient advocates. “A Celebration of Science” will do more than honor the past. Participants will be developing specific nonpartisan proposals designed to help strengthen future American science.
Unfortunately, the government doesn’t always see the full benefit in funding science. No matter how wondrous the drug, no matter how many lives it saves, enhances, lengthens or makes more productive, the development costs supported by federal grants fall only into the expense column when scored by the Office of Management and Budget or the Congressional Budget Office.
Yet scientific breakthroughs, combined with public-health advances, underlie what is arguably the greatest accomplishment in human history: World-wide average life expectancy has more than doubled since 1900. This has fostered major social benefits and economic growth in this country and many others. Consider East Asia, where life expectancy went to about 70 from 39 over the past half century. As Eli Lilly CEO John Lechleiter told this newspaper last year, that might go a long way toward explaining the Asian economic boom.
The United States science ecosystem—defined by collaborations among public agencies, for-profit companies, nonprofit organizations and academic research centers—still leads the world and provides benefits to every nation. But there’s no guarantee that will always be the case. Science magazine reported earlier this year that China already surpasses us in gene-sequencing capacity. Meanwhile, a 2012 National Research Council report said that American research universities “face critical threats and challenges that may seriously erode their quality.” These include financial pressures and increased international competition—two of many concerns behind this weekend’s science initiative.
Much of the work over the next three days will focus on the biological sciences and their capacity to deal with major global issues. In addition to addressing the enormous human and economic toll of disease, the biological sciences also promise to help solve many seemingly intractable global issues—lack of access to abundant food and clean water, the defense against pandemics and bioterrorism, reliable energy supplies and environmental sustainability. Each of these issues profoundly affects economic growth.
Can we afford to invest in bioscience? Don’t we have a budget crisis that’s about to drive us off a fiscal cliff? We do, and we must deal with that through the political process. But there is an important role for government in fostering basic science, which not only saves lives but also improves quality of life. Bioscience in particular provides sustained long-term benefits through job creation, increased productivity, lower health-care costs, longer working lives, process efficiencies and cheaper energy.
When government budget officials view the National Institutes of Health as a $31 billion cost, they don’t count the net benefit. Others do. Research by University of Chicago economists Kevin Murphy and Robert Topel, for instance, indicates that improvements in health from 1970 to 2000—many of them driven by NIH grants—add a whopping $3.2 trillion a year to U.S. national wealth.
Here’s one example: If the incidence of AIDS had continued to grow at the rate of 1980s cases, the majority of hospital beds would have been filled with HIV-positive patients within a decade. According to former NIH Director Elias Zerhouni, the cumulative cost would have exceeded $1.4 trillion. Instead, $10 billion of federally funded research helped turn a certain death sentence into a manageable disease.
Here’s another: From 1950 to 2004, the cumulative budget of the National Cancer Institute (in 2004 dollars) was about $116 billion. In 2004, cancer mortality fell by 2%. Messrs. Murphy and Topel had earlier estimated that a 2% reduction in cancer deaths is worth nearly $1 trillion to the national economy in productive lives saved, which is more than eight times the entire NCI budget for 55 years.
Having made this substantial investment in bioscience, the American people should reap its benefits. Let’s not put the brakes on this engine of job creation and progress.
Just in my lifetime, federally supported research has helped eradicate polio and smallpox, nearly eliminated death from some cancers, and greatly reduced the burden of, and early death from, heart disease. The next decade promises even greater breakthroughs. Now that we’ve begun unlocking the secrets of the human genome, medical researchers have led us to the era of precision medicine—therapies customized to treat you, not your disease.
It may be easier to comprehend these benefits in terms of a single family. You’ve probably never heard of the Beery twins—Alexis and Noah—who were mistakenly diagnosed with cerebral palsy at age two and during the next 12 years suffered a range of almost-fatal symptoms that often left them unable to engage in childhood activities. The remarkable story since then of these now-athletic California teenagers shows how rapidly medical technology has developed with help from federal grants.
Although the original sequencing of the human genome took 13 years and cost $3 billion, genome mapping now takes only a few hours and the cost is rapidly heading toward $1,000. Last year, a team at the Baylor College of Medicine sequenced the Beery family genome and found a rare-but-treatable genetic defect. The twins, now diagnosed with a disorder called dopa-responsive dystonia, aren’t yet cured, but with treatment they no longer face imminent death and live near-normal lives.
Those breakthroughs are part of America’s No. 1 source of growth—basic, translational and clinical science. And the benefits don’t stop at the border. The advances emerging from American laboratories are some of our best ambassadors throughout the world. Their impact is greater than all the foreign aid we’ve ever dispensed.
This is our choice: Invest now to extend the nation’s past achievements, or pass the economic and social burdens of disease to the next generation. It’s time to reaffirm our commitment.
Mr. Milken is chairman of FasterCures, the Milken Institute center for accelerating medical solutions and a host of this weekend’s conference.
A version of this article appeared September 7, 2012, on page A15 in the U.S. edition of The Wall Street Journal, with the headline: Investing in Science, Reaping Rewards.
Copyright 2012 Dow Jones & Company, Inc. All Rights Reserved
September 11, 2012
By GINA KOLATA
The New York Times, New York, NY
Published: September 9, 2012
The first large and comprehensive study of the genetics of a common lung cancer has found that more than half the tumors from that cancer have mutations that might be treated by new drugs that are already in the pipeline or that could be easily developed.
For the tens of thousands of Americans with that cancer — squamous cell lung cancer — the results are promising because they could foretell a new type of treatment in which drugs are tailored to match the genetic abnormality in each patient, researchers say.
“This is a disease where there are no targeted therapies,” said Dr. Matthew Meyerson of the Dana-Farber Cancer Institute in Boston, referring to modern drugs that attack genetic abnormalities. He is a lead author of a paper on the study, with more than 300 authors, which was published online in the journal Nature on Sunday.
“What we found will change the landscape for squamous cell carcinoma,” Dr. Meyerson said. “I think it gives hope to patients.”
The study is part of the Cancer Genome Atlas, a large project by the National Institutes of Health to examine genetic abnormalities in cancer. The study of squamous cell lung cancer is the second genetic analysis of a common cancer, coming on the heels of a study of colon cancer.
The work became feasible only in the past few years because of enormous advances in DNA sequencing that allow researchers to scan all the DNA in a cell instead of looking at its 21,000 genes one at a time. The result has been a new comprehension of cancer as a genetic disease, defined by DNA alterations that drive a cancer cell’s growth, instead of a disease of a particular tissue or organ, like a breast, the prostate or a lung.
And, in keeping with the genetic view of cancer, no one mutation in this study of squamous cell lung cancer stood out — different patients had different mutations.
As a result, the usual way of testing drugs by giving them to everyone with a particular type of cancer no longer makes sense. So researchers are planning a new type of testing program for squamous cell cancer that will match the major genetic abnormality in each patient with a drug designed to attack it, a harbinger of what many say will be the future of cancer research.
Squamous cell lung cancer kills about 50,000 Americans each year. That is more people than are killed in the nation by breast cancer, colon cancer or prostate cancer. Well over 90 percent of squamous cell cancer patients are or were smokers.
The new study compared tumor cells from 178 squamous cell lung cancer patients with the patients’ normal cells. More than 60 percent of the tumors had alterations in genes used to make enzymes that are particularly vulnerable to the new crop of cancer drugs. Many of the drugs are already available or are being tested on other cancers.
These enzymes function like on-off switches for cell growth, said Dr. Roy S. Herbst of Yale Cancer Center, who was not an author of the new study. When they are mutated, the switches are stuck in an on position. About a dozen companies, Dr. Herbst added, have drugs that block these mutated enzymes.
Yet even though the squamous cell cancers analyzed in the study often had mutations in genes for these enzymes, the genes and the mutations were different in different patients.
“Unfortunately, what the Cancer Genome Atlas has revealed is that everyone’s cancer could be very different,” said Dr. William Pao, a lung cancer researcher at the Vanderbilt-Ingram Cancer Center in Nashville and an author of the new paper. “The field is really moving toward personalized medicine.”
The study also found a real surprise, Dr. Meyerson said, something that had not previously been seen in any cancer. About 3 percent of the tumors had a gene mutation that might allow them to evade the immune system. By coincidence, an experimental drug that unleashes the immune system was recently tested in lung cancer patients. Some of those who did not respond might have the mutation, he said.
Now the challenge is to put the findings to clinical use.
First, researchers have to establish that the mutations in question actually are essential to the tumors’ growth, said Dr. Bruce Evan Johnson, a lung cancer researcher at Dana-Farber and an author of the new paper. There are several steps: show that if the mutated gene is added to normal cells, they turn into cancerous cells; show that if the mutated gene is added to mice, they develop squamous cell lung cancer; and show that if the gene is turned off — with a drug, for example — in cells grown in a laboratory, the cells die.
Then come drug tests in patients. But if only a small percentage of patients have each of the mutations, that poses a problem. Ordinarily a few medical centers would enroll patients with a particular type of cancer, like squamous cell. But if, instead, squamous cell patients are subdivided according to their gene mutations, there would be too few for a drug test within a single institution or even several.
So the plan is to cast a wider net. The major medical centers intend to form a consortium. In it, each center would direct one or more studies of one mutation and one drug that might home in on the specific mutation. So even though only a small percentage of squamous cell cancer patients would have that mutation, patients across the country could be in a clinical trial of a targeted drug. A patient’s own doctor could administer the drug, and the medical center directing the trial could analyze the data in partnership with the company that makes the drug.
That sort of system worked for another common type of lung cancer, adenocarcinoma, Dr. Johnson said, allowing researchers to test drugs that work for only 2 to 3 percent of patients.
And the work can move fast, he added. A Pfizer drug, crizotinib, which targets a rearranged gene in some adenocarcinomas, entered clinical trials in 2008 for lung cancers with the rearrangement. The results were reported in 2009 and were published in 2010. Crizotinib was approved in 2011 for patients with the gene rearrangement. The rearrangement is so rare that about 1,500 patients were tested to find 82 whose cancer had it. They were the ones included in the study.
For Pfizer, the experience was transformative.
“The old way of doing clinical trials where patients are only tied together by the organ where their cancer originated, those days are passing,” said Dr. Mace Rothenberg, senior vice president of Pfizer oncology.
Dr. Johnson, too, sees it as a wave of the future.
“That was the first time we really went after the genetic abnormality,” he said.
Now, he said, with squamous cell cancer, “we are sort of where we were four or five years ago with adenocarcinoma.”
August 22, 2012
Lung Cancer Workshop – Progress Toward Translation
Contributed by: Evi Bachrach Makovsky, Merel Grey Mountain, Kim Norris, Christie Pratt, Elda Railey, Deb Violette
A decade ago, treatment decisions for lung cancer were based on tumor histology, whether a patient has non-small cell lung cancer or small cell lung cancer. Through advancements in the fields of proteomics and genomics, we have a better understanding about the complexity of lung cancer and its molecular subtypes. This new understanding has led to an age of personalized and molecularly-targeted treatment approaches. Treatment is no longer a one size fits all approach instead this understanding of genetic make-up of tumors is leading to improved options and outcomes for patients. Researchers have gained a better understanding for how cancer develops, what drives cancer growth and who is more likely to respond to a specific therapy with fewer side effects. Research continues to further classify lung cancer sub populations and to identify therapeutic options through clinical trials.
And even greater is the research that it be conducted in the lab, research with Vitamin D3 and how that relates to patients with COPD, and even more astonishing is tests that may reveal whether or not one will need chemotherapy after surgery. What about the studies with immunotherapy. Can this treatment be effective. Is it effective to use targeted therapies on early lung cancer or should they take a wait and watch approach
SPORE programs and scientists are working hard to answer these questions and bring discoveries from the laboratory to the clinic. Over 100 scientists and patient advocates met at the University of Pittsburgh Hillman Cancer Center on July 16-18, 2012. This meeting was an opportunity for efforts to formally share findings and promote collaborative, interdisciplinary translational cancer research. This meeting emphasized how important innovation and collaboration have been to the progress achieved in the field. Patient advocates were invited to this meeting and played an integral part by providing the patient perspective during the workshop. Presentations included keynote talks about targeted therapies for SCLC (Small Cell Lung Cancer) and molecular portraits or “Clades” to give insight to acquired vulnerabilities of lung cancer. Other sessions presented information on:
- Squamous Cell Lung Cancer
- Tumor Microenvironment and Inflammation
- Collaborative SPORE Initiatives:
- The Lung Cancer Mutation Consortium (LCMC) represents the largest national initiative to prospectively examine non-small cell lung cancer tumors, and match patients to the best possible therapies. Currently, the LCMC includes 14 leading cancer centers across the country. The primary goal is to provide the most up-to-date care for lung cancer patients, while collecting valuable information about the frequency and characteristics of abnormalities found in lung tumors to further improve patient care. The consortium has also built an infrastructure for genomically-based clinical trials available through LCMC member institutions. For more information about the Lung Cancer Mutation Consortium, please visit www.golcmc.com. The LCMC was initiated by NIH/NCI grant funding and support from the National Lung Cancer Partnership has enabled expansion of the consortium.
- Detection of Early Lung Cancer Among Military Personnel (DECAMP) consortium which is funded by a grant from the U.S. Department of Defense (DOD). DECAMP is a multidisciplinary, translational research program. It is designed to develop and validate molecular biomarkers for the early detection of lung cancer among active military personnel and veterans.
- Strategic Partnering to Evaluate Cancer Signatures (SPECS) Program at NIH/NCI was established to address an urgent need for treatment improvements for squamous carcinoma (SCC) of the lung as most of the therapy improvements today occurs for non-SCC patients. In order to facilitate biological research and clinical trials for this subgroup of patients we established the Squamous Lung Cancer Consortium (SLCC), which includes 8 different academic institutions in North America and Canada. The consortium was established through a grant application for the Strategic Partnering to Evaluate Cancer Signatures (SPECS) Program at NIH/NCI, which was awarded in February 2012.
- Lung Cancer Risk Assessment and Early Detection
- New Targets for Lung Cancer Therapy
- Systems Biology
- Intrinsic and Acquired Resistance to Agents
What is a SPORE?
SPORE grants involve both basic and clinical/applied scientists and support projects that will result in new and diverse approaches to the prevention, early detection, diagnosis and treatment of human cancers. Each SPORE is focused on a specific organ site or on a group of highly related cancers, such as gastrointestinal cancers and sarcomas. SPOREs are designed to enable the rapid and efficient movement of basic scientific findings into clinical settings, as well as to determine the biological basis for observations made in individuals with cancer or in populations at risk for cancer.
Currently there are seven Lung SPOREs:
- Dana-Farber Harvard Cancer Institute
- H. Lee Moffitt Cancer Center and Research Institute
- Johns Hopkins University
- University of Colorado Cancer Center
- University of Pittsburgh
- University of Texas/ Southwestern Medical Center/ MD Anderson Cancer Center
- Vanderbilt University
Currently 18 patient advocates are involved with Lung SPORES and meet regularly via teleconference with the Lung SPORE directors.
For more information about the Lung SPORE program go to http://trp.cancer.gov/spores/lung.htm
June 21, 2012
Pfizer Announces Positive Results From Phase 3 Study PROFILE 1007 Evaluating XALKORI® (crizotinib) In Previously Treated Patients With ALK-Positive Advanced Non-Small Cell Lung Cancer
— Detailed Study Results to be Presented at an Upcoming Medical Congress
NEW YORK, N.Y., June 19 – Pfizer Inc. announced today that the PROFILE 1007 study met its primary endpoint, demonstrating that XALKORI® (crizotinib) significantly improved progression-free survival (PFS) when compared with pemetrexed or docetaxel, in previously treated patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC). PROFILE 1007 is the first randomized Phase 3 study in ALK- positive advanced NSCLC patients.
“These results are important because they demonstrate, for the first time, that XALKORI is superior to standard chemotherapy in prolonging survival without progression in patients with previously-treated ALK-positive advanced NSCLC,” said Dr. Mace Rothenberg, senior vice president of Clinical Development and Medical Affairs for Pfizer’s Oncology Business Unit. “This study provides further support for the precision medicine approach to drug development being taken at Pfizer by demonstrating how knowledge about the underlying genetic abnormalities within a cancer can be used to improve the standard of care for that disease.”
The adverse events observed on crizotinib and chemotherapy in PROFILE 1007 were generally consistent with their respective known adverse event profiles. Full efficacy and safety data from this study will be presented at an upcoming medical congress.
Ongoing Studies of XALKORI®
Pfizer is committed to the development program for XALKORI, and continues to study the therapy in several ongoing trials including PROFILE 1014 (A8081014), a Phase 3, open-label, randomized, two-arm study to evaluate the safety and efficacy of XALKORI in comparison with pemetrexed plus cisplatin or carboplatin in patients previously untreated for ALK-positive advanced NSCLC.1 In addition, PROFILE 1005 (A8081005)is an ongoing Phase 2 open-label, single-arm study on the efficacy and safety of XALKORI in patients with ALK-positive advanced NSCLC who have failed more than one line of treatment with prior chemotherapy.2 For more information on these clinical trials, please contact the Pfizer Oncology Clinical Trial Information Service at 1-877-369-9753 (US/Canada), via email at PfizerHPTrials@emergingmed.com or visit www.pfizercancertrials.com.
About Non-Small Cell Lung Cancer
Worldwide, lung cancer is the leading cause of cancer death in both men and women.3 In Europe, lung cancer accounts for 20 percent of all cancer-related deaths.4 NSCLC accounts for about 85 percent of lung cancer cases and remains difficult to treat, particularly in the metastatic setting.5 Approximately 75 percent of NSCLC patients are diagnosed late with metastatic, or advanced, disease, where the five-year survival rate is only 6 percent.6,7,8
XALKORI received an accelerated approval by the U.S. Food and Drug Administration (FDA) for the treatment of locally advanced or metastatic NSCLC that is ALK-positive as detected by an FDA- approved test. This indication is based on response rate. There are no data available demonstrating improvements in patient reported outcomes or survival with XALKORI. XALKORI also has received approval in a number of other countries including Canada, Korea, Japan and Switzerland.
XALKORI has played a significant role in advancing the treatment of personalized medicine in NSCLC and has rapidly become a standard of care in ALK-positive advanced NSCLC. XALKORI blocks signaling in a number of cellular pathways that are believed to be critical for the growth and survival of tumor cells, which may lead to stabilization or regression of tumors.3,9 Alterations in the ALK gene are believed to be a key driver of tumor development in cancers like NSCLC.10 Although ALK rearrangement is known to occur more frequently in patients with non-squamous cell carcinoma and histories of light or never smoking, it has also been shown to occur in smokers and in patients with squamous cell carcinoma histology.11 Alterations in the ALK gene can occur independent of age, gender, ethnicity and smoking history.12
XALKORI has demonstrated inhibition of c-MET, the hepatocyte growth factor receptor, and its activity is under investigation.12 XALKORI has also been shown to demonstrate a response in a Phase 1 trial in advanced NSCLC patients whose tumors have the ROS-1 gene rearrangement and its activity is continuing to be studied in this patient population.13 For more information and full prescribing information please visit www.XALKORI.com.
Important XALKORI® Safety Information
Drug-induced hepatotoxicity with fatal outcome has occurred. Transaminase elevations generally occurred within the first 2 months of treatment. Monitor with liver function tests including ALT and total bilirubin once a month and as clinically indicated, with more frequent repeat testing for increased liver transaminases, alkaline phosphatase, or total bilirubin in patients who develop transaminase elevations. Temporarily suspend, dose reduce, or permanently discontinue XALKORI as indicated.
XALKORI has been associated with severe, life-threatening, or fatal treatment-related pneumonitis in clinical trials with a frequency of 4 in 255 (1.6%) patients. All of these cases occurred within 2 months after the initiation of treatment. Monitor patients for pulmonary symptoms indicative of pneumonitis. Exclude other causes and permanently discontinue XALKORI in patients with treatment-related pneumonitis.
QTc prolongation has been observed. Avoid use of XALKORI in patients with congenital long QT syndrome. Consider periodic monitoring with electrocardiograms (ECGs) and electrolytes in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, or who are taking medications that are known to prolong the QT interval. Permanently discontinue XALKORI for grade 4 QTc prolongation. XALKORI should be withheld for grade 3 QTc prolongation until recovery to ≤ grade 1. Permanently discontinue XALKORI if grade 3 QTc prolongation recurs.
Detection of ALK-positive NSCLC using an FDA-approved test, indicated for this use, is necessary for selection of patients for treatment with XALKORI.
XALKORI can cause fetal harm when administered to a pregnant woman based on its mechanism of action. Women of childbearing potential should be advised to avoid becoming pregnant while receiving XALKORI. If the patient or their partner becomes pregnant while taking this drug, apprise the patient of the potential hazard to the fetus.
Among the 397 patients for whom information on deaths and serious adverse reactions is available, deaths within 28 days of the last dose of study drug occurred in 45 patients. Ten (2.5%) patients died within 28 days of their first dose of study drug. Causes of death included disease progression (32 patients), respiratory events (9), and other (4).
Safety of XALKORI was evaluated in 255 patients with locally advanced or metastatic ALK-positive NSCLC in 2 single-arm clinical trials (Studies A and B). The most common adverse reactions (≥25%) across both studies were vision disorder, nausea, diarrhea, vomiting, edema, and constipation. Grade 3-4 adverse reactions in ≥4% of patients in both studies included ALT increased and neutropenia.
Vision disorders including visual impairment, photopsia, vision blurred, vitreous floaters, photophobia, and diplopia were reported in 159 (62%) patients in clinical trials. Consider ophthalmological evaluation, particularly if patients experience photopsia or experience new or increased vitreous floaters. Severe or worsening vitreous floaters and/or photopsia could also be signs of a retinal hole or pending retinal detachment. Advise patients to exercise caution when driving or operating machinery due to the risk of developing a vision disorder.
About Pfizer Oncology
Pfizer Oncology is committed to the discovery, investigation and development of innovative treatment options to improve the outlook for cancer patients worldwide. Our strong pipeline of biologics and small molecules, one of the most robust in the industry, is studied with precise focus on identifying and translating the best scientific breakthroughs into clinical application for patients across a wide range of cancers. By working collaboratively with academic institutions, individual researchers, cooperative research groups, governments, and licensing partners, Pfizer Oncology strives to cure or control cancer with breakthrough medicines, to deliver the right drug for each patient at the right time. For more information please visit www.Pfizer.com.
DISCLOSURE NOTICE: The information contained in this release is as of June 19, 2012. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.
This release contains forward-looking information about an oncology product, XALKORI (crizotinib), including its benefits, that involves substantial risks and uncertainties. Such risks and uncertainties include, among other things, the uncertainties inherent in research and development; decisions by the European Commission and regulatory authorities in other jurisdictions regarding whether and when to approve drug applications that have been or may be filed for such product as well as their decisions regarding labeling and other matters that could affect its availability or commercial potential; and competitive developments.
A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2011 and in its reports on Form 10-Q and Form 8-K.
1 ClinicalTrials.gov. A Clinical Trial Testing The Efficacy Of Crizotinib Versus Standard Chemotherapy Pemetrexed Plus Cisplatin Or Carboplatin In Patients With ALK Positive Non Squamous Cancer Of The Lung (PROFILE 1014). Available at: http://clinicaltrials.gov/ct2/show/NCT01154140?term=pemetrexed+crizotinib&rank= 3. Accessed May 31, 2012.
2 ClinicalTrials.gov. An Investigational Drug, PF-02341066, Is Being Studied In Patients With Advanced Non-Small Cell Lung Cancer With A Specific Gene Profile Involving The Anaplastic Lymphoma Kinase (ALK) Gene. Available at: http://clinicaltrials.gov/ct2/show/NCT00932451?term=crizotinib+AND+Anaplastic+L ymphoma+Kinase&rank=5. Accessed May 31, 2012.
3 World Health Organization. Cancer fact sheet. http://www.who.int/mediacentre/factsheets/fs297/en/. Accessed May 31, 2012. 4 European Lung Foundation. What is Lung Cancer? Available at: http://www.european-lung-foundation.org/index.php?id=65. Accessed May 31, 2012. 5 American Cancer Society. Detailed Guide: Lung Cancer (Non-Small Cell). Available at: http://www.cancer.org/acs/groups/cid/documents/webcontent/003115- pdf.pdf. Accessed July 12, 2011. 6 Yang P, Allen MS, Aubry MC, et al. Clinical features of 5,628 primary lung cancer patients: experience at Mayo Clinic from 1997 to 2003. Chest. 2005;128(1):452–462. 7 Govindan R, Page N, Morgensztern D, et al. Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol. 2006;24(28):4539–4544. 8 American Cancer Society. Detailed guide: lung cancer – non-small cell. Non- small cell lung cancer survival rates by stage. http://www.cancer.org/Cancer/LungCancer-Non-SmallCell/DetailedGuide/non-small- cell-lung-cancer-survival-rates. Accessed February 8, 2011. 9 Chiarle R, Voena C, Ambrogio C et al. The anaplastic lymphoma kinase in the pathogenesis of cancer. Nat Rev Cancer. 2008;8(1): 11-23. 10 Zou HY, Li Q, Lee JH, et al. An orally available small-molecule inhibitor of c-MET, PF-2341066, exhibits cytoreductive antitumor efficacy through antiproliferative and antiangiogenic mechanisms. Cancer Res. 2007;67:4408-4417. 11 Choi Y et al. Mutations of EML4-ALK in Lung Cancer That Confer Resistance to ALK Inhibitors. The New England Journal of Medicine. October 28, 2010 12 Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 2007;448:561-566. 13 ASCO Accepted Abstract #7508. Clinical activity of crizotinib in advanced non- small cell lung cancer (NSCLC) harboring ROS1 gene rearrangement. Clinical Science Symposium. Alice T. Shaw. Saturday, June 2, 2012. 8:00 AM – 8:15 AM.
June 18, 2012
Case report warns the relatively new treatment killed airway tissue in woman with early-stage disease
June 13, 2012
By Jenifer Goodwin
WEDNESDAY, June 13 (HealthDay News) — A woman with early-stage lung cancer died recently after highly targeted radiation therapy zapped not just her tumor, but surrounding tissue, fatally damaging her airway.
Though just a single case report of an apparently deadly complication, the authors warn that targeted radiation therapy — specifically, stereotactic body-radiation therapy — has inherent risks, even when done properly and using an even lower dose of radiation than is considered safe.
Stereotactic body-radiation therapy focuses beams of radiation on a tumor in the hopes of killing it. Because it uses highly precise beams that can focus large doses of radiation with millimeter accuracy, the technique is considered an advance over older types of radiation therapy, which are generally more diffuse, explained Dr. Len Lichtenfeld, deputy chief medical officer for the American Cancer Society. The goal is to reduce exposure of healthy tissue to the radiation to avoid side effects, while more effectively shrinking the tumor with the higher doses of radiation delivered over a shorter period of time.
Stereotactic radiation is increasingly used to treat early-stage lung cancer. Though the first choice of treatment for early-stage lung cancer is surgery, radiation is turned to in people who cannot withstand having a portion of their lung removed because of other health issues, such as serious underlying heart or lung disease, said Dr. Ramesh Rengan, an assistant professor of radiation oncology at University of Pennsylvania Perelman School of Medicine.
Rengan wrote the case report published in the June 14 issue of the New England Journal of Medicine.
In the case report, a 61-year-old woman with a history of smoking and stage 1 adenocarcinoma — meaning the two tumors were small and had not spread to the lymph nodes or other organs — was treated, seemingly successfully, with stereotactic body radiation. Adenocarcinoma is a common type of non-small cell lung cancer.
But eight months later, not only did the woman have new metastases (spread of the cancer), a bronchoscopy — a camera threaded into the airway — showed an “extensive area of necrosis,” or dead tissue, near the radiated area.
Her physicians at University of Pennsylvania did not do additional radiation. Instead, she underwent more chemotherapy, but began coughing up blood and died a few months later.
Researchers warned that patients with tumors near “radiation-sensitive” body parts, or body parts easily damaged by radiation relative to the dose needed to treat the cancer, such as the large airways, large blood vessels, the heart, certain nerves and the spinal cord, “may be at increased risk for severe radiation injury.”
“The reason why it’s so important to get this message out is because these side effects don’t manifest themselves immediately. They can take months to show up,” Rengan said. “And you will only find them if you are looking. Most patients aren’t undergoing bronchoscopy just for the heck of it. On a CT scan, the airway looks fine.”
Rengan urged physicians who use stereotactic radiation to follow patients carefully. Furthermore, the levels of radiation that are considered safe may need to be rethought, he added.
“This was a dose level that was previously believed to be safe for this type of tumor in this location,” he said.
Lichtenfeld praised the authors for writing the case report. Although one report does not have the weight of a clinical trial involving multiple patients from multiple institutions, anecdotal reports such as this can help raise awareness about the potential complications of a treatment that’s increasingly popular.
“Even though the doctors gave the radiation properly, they still got a serious complication,” Lichtenfeld said. “What this report is saying is even though we did this the right way, doctors and patients still need to be aware you can have bad effects from this type of radiation used in this way.”
The U.S. National Cancer Institute <http://www.cancer.gov/cancertopics/types/lung> has more on lung cancer.
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