Dr. John Mendelsohn, Chairman, Worldwide Innovative Networking (WIN) Consortium in personalized cancer medicine
“Our mission is to rapidly translate personalized cancer medicine discoveries into standards of patient care worldwide.” Dr. John Mendelsohn, Chairman, Worldwide Innovative Networking (WIN) Consortium in personalized cancer medicine

WIN Consortium
“We are very sad to announce that our Vice-Chairman, Prof. Thomas Tursz has passed away on April 27, 2018. Join us at the WIN 2018 symposium June 25-26, Paris where a session will be dedicated to celebrating his life and achievements.” WIN Consortium

WINning together

WIN was formed on the premise that we can accomplish more together than each organization can achieve working alone. We aim to improve cancer patients’ survival and quality of life. View WIN's history and unique attributes:

WIN represents a global collaboration of cancer centers, life science and biotech organizations, pharmaceutical and technology companies, health plans, and not-for-profit organizations.
The Worldwide Innovative Networking (WIN) Consortium in personalized cancer medicine was initiated in 2010 with leadership from leading cancer centers worldwide. WIN is a non-profit, non-governmental organization headquartered in Paris.

WIN was created to accelerate the pace and reduce the cost of translating novel cancer treatments to the bedside by developing and applying, through worldwide clinical trials and research projects, the most promising advances in genomic-based cancer research. WIN aims to initiate research projects each year in a global consortium guided by an independent scientific advisory board.

WIN now includes 43 institutional members. These stakeholders have come together from all parts of the world to address the challenge of increasing the efficacy of cancer diagnostics and therapeutics by understanding the genetics and biology of each individual’s tumor and accounting for genetic differences across diverse populations—from North and South America, Europe, Asia, and the Middle East.

Our goal is to significantly improve outcomes for patients around the globe. We aim to increase the number of patients worldwide that have access to innovative, global clinical trials in the area of genomic-based cancer therapeutics. Global diversity and inclusion of all stakeholders is WIN’s most important and differentiating asset.
WIN is comprised of organizations representing all stakeholders in personalized cancer medicine.
WIN enables cross-sector collaborations designed to accelerate the speed and efficacy with which breakthroughs in personalized cancer medicine can be realized and brought to patients worldwide.

Our members include leading academic, pharmaceutical, life science, not-for-profit, health IT, and healthpayer organizations.
Our members include 30 leading academic centers representing 18 countries and four continents, enabling coordinated studies with a global patient population.
The response to a genetically-targeted therapy can vary due to differences in ethnicity and environment. WIN's global studies are designed to identify and account for this variability, enhancing the speed and efficacy with which novel discoveries can be made and brought to patients around the world.

WIN's first trial, WINTHER, is currently being carried out through a collaboration between six academic centers in five countries, with key support from Europe (EUFP7), Fondation ARC, Pfizer and other pharma companies.
WIN prioritizes cross-sector interaction designed to enhance learning across and between continents and healthcare sectors.
WIN Symposia, held annually in Paris, brings together hundreds of leaders representing all stakeholders from around the world in a forum designed to promote the exchange of ideas and information.

Clinical trials and projects

WIN members collaboratively design and carry out global studies designed to achieve breakthroughs for patients worldwide. Our distinguished Scientific Advisory Board oversees WIN studies. Current trials include:

SPRING 01 (Survival Prolongation by Rationale Innovative Genomics) proof of concept trial is the first trial exploring the tri-therapy strategy in first line of advanced/metastatic non-small cell lung cancer (NSCLC), following the historical success of this approach in AIDS and tuberculosis for which only tri-therapy demonstrated long term efficacy.
The WIN SPRING trial will be conducted in the USA, France, Spain, Luxembourg and Israel in the following cancer centers: University of California - San Diego's Moores Cancer Center, Avera Cancer Institute (Sioux Falls, Arizona), Institut Curie (Paris), Centre Léon Bérard (Lyon), Hôpital Paris Saint-Joseph (Paris), Vall d'Hebron Institute of Oncology (Barcelona), Centre Hospitalier de Luxembourg (Luxembourg), and Chaim Sheba Medical Center (Israel).

The trial is sponsored by the WIN Consortium and funded by ARC Fondation for cancer research (France). The drugs are donated by Pfizer Inc.
WINTHER, the WIN Consortium's first global personalized cancer medicine trial, is an ongoing global study carried out at multiple leading academic cancer centers around the world.
WINTHER aims to validate a breakthrough concept that would offer treatment guided by each patients biology for the vast majority of cancer patients.

With multiple cancer centers representing four countries - as well as partner biotech and pharma companies - WINTHER exemplifies WIN's commitment to innovative, collaborative studies that make effective, personalized medicine a reality for patients worldwide.
WIN is currently planning innovative global clinical trials that represent the next generation of studies focused on lung cancer.
European funded trials WINTHER EU FP7 funded and CHEMORES EU FP6 funded established foundations for WIN future global strategy for lung cancer currently under development.

The concept underlying the new strategy is developed in the following publications:
WIN provides a legal and fundraising framework that enables collective fundraising while protecting its members' intellectual property.
The WIN platform enables multiple organizations from different sectors to productively collaborate while providing for the protection of intellectual property. Each project or clinical trial has its own specific contract or funding mechanism.

People leadership

WIN leaders are selected for their contributions and commitment to making effective, personalized cancer medicine a reality for patients around the world. They guide WIN's strategic, operational, and scientific direction.

John Mendelsohn Photo
Chairman
John Mendelsohn

Director, Khalifa Institute for Personalized Cancer Medicine and Past-President, the University of Texas MD Anderson Cancer Center (USA)

Richard L. Schilsky Photo
Chairman, WIN Scientific Advisory Board
Richard L. Schilsky

Senior Vice President and Chief Medical Officer, American Society of Clinical Oncology (ASCO); Chairman, WIN SAB

Razelle Kurzrock Photo
Chair, Clinical Trials Committee
Razelle Kurzrock

Chief, Division of Hematology & Oncology, Sr. Deputy Center Director for Clinical Science, University of California San Diego Moores Cancer Center (USA)

Vladimir Lazar Photo
Chief Scientific and Operating Officer
Vladimir Lazar

Chief Scientific and Operating Officer, WIN Consortium


Our members

WIN members include 43 leading organizations representing all stakeholders in personalized cancer medicine covering 21 countries and 4 continents. Our shared vision is delivering the promise of effective, personalized cancer medicine to patients worldwide.


WIN Symposia

WIN Symposia, held annually in Paris, gather leaders representing a breadth of stakeholders from around the world to learn, share, and collaborate. Visit http://www.winsymposium.org for registration and additional information.

WIN 2018 Symposium logotype

WIN 2018 Symposium

June 25, 2018 - June 26, 2018

We are excited to celebrate our 10th year Anniversary edition of the WIN Symposia at the WIN Symposium 2018 in Paris, France on 25-26 June 2018.

The WIN Symposium Organizing Committee has chosen “Global Implementation of Precision Oncology: WINning the War against Cancer” as the theme for this celebratory event.

For more details, please visit our dedicated symposium website: https://www.winsymposium.org

WIN 2017 Symposium logotype

WIN 2017 Symposium

June 26, 2017 - June 27, 2017

The WIN 2017 Symposium with the theme ‘Expediting Global Innovation in Precision Cancer Medicine’ was held in Paris, France, June 26-27, 2017. The overarching goal of our symposium was to share information to promote and accelerate cutting edge investigations and use of personalized, targeted cancer therapy.

WIN 2016 Symposium logotype

WIN 2016 Symposium

June 27, 2016 - June 28, 2016

The WIN 2016 Symposium “Innovative Approaches to Improve Cancer Patient Outcomes”, June 27-28th was the eighth in a series of symposia dedicated to advancing personalized cancer medicine. It was a successful unique forum that brought leaders representing all stakeholders - academia, pharma, biotech / life sciences, regulatory, and health payer - together from around the globe.


What people are saying


WIN Consortium Applies Transcriptomics to Bolster Patient Matching in Precision Oncology Study
CHICAGO (GenomeWeb) – The combination of DNA and RNA analysis allowed more cancer patients to be matched to precision medicine options than would have been possible based on DNA analysis only, a study presented at the American Society of Clinical Oncology’s annual meeting showed.

Although the WINTHER study, conducted by the WIN Consortium, did not meet a prespecified clinical benefit endpoint, a blinded, post-hoc analysis showed that when patients received treatments they were most likely to benefit from, as determined by high matching scores, they lived significantly longer compared to those who did not get the top-matched therapies. The WINTHER investigators said the data demonstrate the importance of integrating transcriptomics into precision oncology trials alongside DNA analysis.

In the WINTHER study, conducted by the WIN Consortium, 35 percent of 303 consented advanced cancer patients matched to a treatment. First, patients were tested for targetable alterations in cancer genes using Foundation Medicine's FoundationOne test. Those who weren’t matched to targetable drugs based on detected genetic alterations had another shot at getting matched to a treatment based on the differences in gene expression in the tumor and normal samples (assessed by microarrays). Without the RNA-based algorithm, the match-rate would have been 23 percent.

"One of the issues with precision medicine trials has been the low matching rate," Razelle Kurzrock, co-leader of the WINTHER trial and director of the Center for Personalized Cancer Therapy & Clinical Trials Office at the University of California, San Diego's Moores Cancer Center, told GenomeWeb. However, the match-rate seen in WINTHER is high for a precision medicine trial, she said, given that most other studies have placed between five percent and 25 percent of patients on to treatment arms after DNA profiling.

"As there are more drugs available and people gain more experience, and in particular, by adding transcriptomics, we are increasing the percentage of patients matched," Kurzrock said.

The aim of the WINTHER study was to use transcriptomics to try to bolster the number of patients receiving personalized therapies. Out of 303 consented patients, ultimately 107 patients were treated, 69 based on DNA profiling and 38 based on RNA profiling.

Although a high match rate is often touted as demonstrating the success of the precision oncology paradigm, it ultimately has little value unless patients benefit from the treatment to which they were matched. And in WINTHER, there were a number of difficulties that kept researchers from recruiting the number of patients originally planned and from meeting the study's primary endpoint.

Researchers had aimed to enroll 200 patients — 60 in arm A where patients were tested by FoundationOne and 140 in arm B where patients were matched based on transcriptomics — from America, Europe, and Israel. "Back when we designed this trial, we thought that we would find actionable results in a minority of patients [in arm A,] and that most patients would be treated in arm B," said Jordi Rodon from MD Anderson Cancer Center while presenting the data.

However, the trial was unable to recruit the requisite number of patients in the US due to regulatory delays and funding limitations.

Moreover, researchers set a high bar for themselves in terms of the benefit they wanted patients to experience in the study. They decided to compare the progression-free survival patients had to matched therapies in WINTHER (PFS2) against the progression-free survival they had to the therapy prior to joining the trial (PFS1).

The expectation generally is that with each cancer progression patients will derive less and less benefit from later lines of treatment. "The idea is if PFS2 can be equal to PFS1 then disease is stable," said Vladimir Lazar, chief scientific and operating officer of the WIN Consortium and an investigator on WINTHER. "But if PFS2 is longer than PFS1, then you’ve reversed the tendency of incrementally worse outcomes on subsequent lines of treatment and that shows a clinical benefit."

The patients recruited to WINTHER were heavily pretreated, with 25 percent having had more than five prior lines of therapy. But the investigators had hoped to demonstrate that even such heavily pretreated, advanced cancer patients would benefit more from matched treatment compared to the prior line of therapy. In this regard they hoped to show a PFS2 to PFS1 ratio of greater than 1.5 in 50 percent of patients in arm A and in 40 percent of patients in arm B.

The PFS2/PFS1 ratio "is a powerful way [of showing treatment benefit] because every patient serves as his or her own control," said Lazar, but he noted that the goal in WINTHER to show a ratio greater than 1.5 was far too ambitious when a ratio of greater than 1.3 is well accepted and has been used in prior precision oncology studies, such as MOSCATO.

In WINTHER, this prespecified endpoint was ultimately reached in only 20 percent of patients in arm A and in 22 percent of patients in arm B.

Eddy Yang from the University of Alabama at Birmingham reviewed the WINTHER data at the meeting and commended the investigators for setting a higher bar in terms of the PFS ratio. He noted though that while the PFS ratio "eliminates that variability between patients" when evaluating the benefit of treatment, there are also downsides to using this endpoint. "There are a lot of other factors that can influence this ratio," he said, such as the prior and current treatment given to the patient, whether the previous PFS was measured accurately, and the differences in prognosis between tumor types.

Yang recognized that the increase in the match rate from 23 percent to 35 percent using transcriptomics is significant in that it represents perhaps the highest match rate in a precision oncology trial. The match rate reported in WINTHER, however, was exceeded by another precision oncology study called i-PREDICT, which also released data at the meeting.

In that study, also led by Kurzrock, researchers from the University of California, San Diego, MD Anderson Cancer Center, and elsewhere enrolled approximately 150 advanced cancer patients using the FoundationOne test to gauge 315 genes, and if possible, based on tumor mutational burden, circulating tumor DNA, and PD-L1 status by immunohistochemistry. They reported being able to match 73 patients, or nearly 50 percent, to a targeted drug or immunotherapy combination.

"I think what’s happening, is that precision oncology trials are getting better," Kurzrock said, though she maintained that to the best of her knowledge WINTHER has the highest match rate based on the published data from precision oncology trials. While there was an abstract on i-PREDICT at ASCO, it has not been published on.

Despite the high match rate, the biggest challenge within WINTHER was garnering sufficient tumor content in samples to enable RNA analysis. Although 253 out of 303 consented patients agreed to provide tumor and normal samples, only 158 patients received treatment recommendations based on their FoundationOne results and transcriptomic analysis, largely due to difficulties with procuring sufficient tumor samples for RNA analysis.

Rodon noted that for transcriptomic analysis the sample quality requirements were much more stringent and required 50 percent tumor content. "The consensus is building that RNA is actually very important," Kurzrock said. But because RNA has been more difficult as far as getting adequate samples and processing, she said that not many in the research community have included RNA analysis in precision oncology studies.

In WINTHER, each site had to learn how to process the samples for transcriptomics, but the sites got better at doing this as they gained experience, recalled Kurzrock. In subsequent WIN Symposium trials, researchers hope to avoid the attrition rates seen in WINTHER by using paraffin-embedded samples, which can be microdissected to increase the tumor content.

Another difficulty in WINTHER was with access to drugs. Based on the literature and the Comparative Toxicogenomics Database (a repository of chemical–gene/protein interactions), WIN has amassed a database of genes that are deregulated in cancer and which influence drugs response and resistance. Using this database, researchers are able to identify the targetable genes that are deregulated in each patient's tumor and apply an algorithm to rank the drugs that they might benefit from most.

Patients who matched to an approved or investigational drug based on this algorithm were enrolled in arm B. But Kurzrock estimated that only around 50 percent of patients received the top ranked drug according to DNA and RNA matching.

A clinical management committee reviewed DNA and RNA test results from study participants, but ultimately made recommendations based on patient's comorbidities and whether a particular drug or trial was available at a specific institute or country. "We ranked more than one option for patients, and we discussed with the physician the range of options," Kurzrock said. "And we tried to give the best option considering the reality that existed for that patient."

The reality for many patients in WINTHER, though, was that they didn't get the top treatment option according to molecular testing. So, researchers conducted a post-hoc analysis to evaluate how patients fared when they did receive drugs based on a high matching algorithm for both arms A and B.

"We thought this was very important to do because if patients were not well matched, we wanted to know if that made a difference when they were highly matched versus poorly matched," Kurzrock said, emphasizing that this was a blinded analysis to avoid bias.

For arm A, researcher devised an algorithm — dividing the number of genomic alterations matched by the total number of characterized DNA alterations — to determine which patients got a high matching score. For arm B, they used the RNA algorithm. When investigators compared all treated patients with good performance status and a high matching score against everyone else, the median overall survival was 25.8 months versus 4.5 months, respectively. "This contains an important lesson in that if you give a better matched drug, patients do better," Kurzrock said.

Following Rodon's presentation at the meeting, some oncologists in the audience commended the investigators for using transcriptomics to guide therapy choice, and in particular analyzing gene expression in tumor versus normal samples. Others at the meeting were more reserved in their judgement.

"Doing a transcriptional analysis, looking at that set of drugs, we're not ready yet," said another oncologist from the audience. "Sequencing every patient, it's negligent as an oncologist to do that in advanced cancer patients, not because we can match all patients but because we can match very few as you said. That's evolving at a rapid rate, but to try to push that too hard and talk about effective personalized medicine actually doesn't help the field."

Rodon responded that WINTHER was a learning opportunity and the WIN collaborators are proceeding carefully. The study, for example, only matched patients based on RNA data when they failed to match to a therapy using FoundationOne. Additionally, despite the challenges the study faced in procuring samples with high tumor content, it was apparent that patients are willing to give tumor and normal samples from molecular analysis.

"I’m not saying that on the basis of this one trial transcriptomics can become the standard of care, but the trial definitely suggests that transcriptomics should be an important part of additional clinical trials," Kurzrock said, noting the need for further studies.

The follow-on study to WINTHER will be SPRING, which will investigate the safety and efficacy of giving advanced lung cancer patients a triplet therapeutic strategy based on a biomarker algorithm that matches patients to the combinations. This algorithm incorporates targeted genomic sequencing, copy number variation, transcriptomics, and miRNA expression, and patients will have their normal and tumor tissue analyzed.

Kurzrock reflected that genomic and transcriptomic testing are very rapidly evolving technologies. While some may feel that these tools aren't ready to used broadly in cancer care, "there is more and more evidence, and to me it's pretty compelling evidence, that genomics and now transcriptomics is important for precision medicine trials,” she said.

Turna Ray
Senior Editor, Genomeweb
We are very sad to announce that our Vice-Chairman, Professor Thomas Tursz passed away on Friday, April 27th 2018 at the age of 71. Our thoughts and condolences are with his family and he will be deeply missed.
Professor Thomas Tursz with Dr John Mendelsohn was the visionary founding member of WIN Consortium - Worldwide Innovative Network in personalized cancer medicine, which today brings over 40 institutions together in 20 countries promoting global diversity, cooperation and inclusion of all stakeholders to significantly improve cancer patient survival. He was also the Chairman of the Scientific Advisory Board of one of our members, ARC Foundation for cancer research (France).

Professor Thomas Tursz was a brilliant and passionate doctor and scientist. He played a key role in the description of the oncogene role of the Epstein Barr virus and developed anti-tumor immunotherapy, gene therapy and precision oncology. Professor Thomas Tursz was a visionary spirit who profoundly impacted and influenced today’s oncology.

Born in Krakow, Poland in 1946, Professor Tursz was a widely recognised medical physician, oncologist and researcher with a distinguished career spanning over 46 years. He attained Full Professor of Oncology at the Faculty of Medicine Paris-Sud in 1986. He was General Director of the Institut Gustave-Roussy (IGR) for 16 years (1994-2010). Professor Emeritus of Oncology at the University of Paris-Sud/Paris XI since September 1st, 2011. He held multiple distinguished positions including President of the French Federation of Comprehensive Anticancer Centres (FNCLCC) now known as UNICANCER (2004-2010); Elected Member of the European Academy of Cancer Sciences (since 2009); member of the Scientific Advisory Boards of several major European Cancer Centers.

His work has been awarded with several prestigious scientific prizes such as the Oncology Award "Prix de Cancérologie" from the French National League Against Cancer in 1979, the Bernard-Halpern Immunology Award in 1983, Cancerology Prize of the Academy of Sciences in 1988, the Rosen Oncology Award from the Medical Research Foundation in 1989 and the Grand Prix in Oncology from the Academy of Medicine in 1992, the Hamilton Fairley Award for Clinical Research from the European Society of Medical Oncology (ESMO) in 1998 and the French Radiation Award in 2001 and was Knighted in 2001 and Officer of the Legion of Honor in 2014.

An author of 350 international papers in peer-reviewed journals including Science, Nature, PNAS, New England Journal of Medicine, Journal of Clinical Investigation, Lancet, Lancet Oncology and British Med Journal.

We have modified the program of the WIN Symposium 2018 to include a session dedicated to celebrating the life and achievements of Professor Thomas Tursz. Please join us.
Avera To Enroll First Patients in Landmark Lung Cancer Tri-Therapy Clinical Trial
Sioux Falls,Jan. 19, 2018(GLOBE NEWSWIRE)

SIOUX FALLS, S.D. — The first patients in the world will be able to enroll in a new cancer study at Avera as part of an international collaboration that looks to transform care for lung cancer patients.

This clinical trial that received the approval of the FDA is Avera’s latest collaboration as part its membership in the Worldwide Innovative Networking (WIN) Consortium.

“We’re taking a bold step in a new direction so lung cancer patients have hope for more treatment options after diagnosis. This latest step in our collaboration with WIN represents one clinical trial but is part of our larger goal to revolutionize cancer care through personalized medicine,” said Benjamin Solomon, MD, the lead investigator for the study at Avera and medical oncologist with Avera Cancer Institute. “If successful, this study could lead to a complete paradigm shift in our approach to lung cancer treatment with a goal of realizing big improvements in outcomes for patients.”

More than 60 percent of non-small cell lung cancer cases are detected in an advanced stage, and less than 5 percent of these patients are alive five years after diagnosis.

In the Survival Prolongation by Rationale Innovative Genomics (SPRING) trial, patients will be given a three-drug protocol that incorporates immunotherapy (avelumab) and two other targeted therapies (palbociclib and axitinib). All patients will be given the same drug combination and their response rates will be tracked to see which patients respond best.

Through the WIN Consortium, an Avera research team under Solomon’s leadership has helped design and implement the clinical trial from the ground up.

“This breakthrough research is happening in Sioux Falls, S.D., because of the high level of expertise and commitment available here,” said Vladimir Lazar, MD, PhD, founder and Chief Scientific and Operating Officer of the WIN Consortium. “With these clinical trials we want to go beyond what is now possible so patients around the world can have more hope when they get a lung cancer diagnosis.”

Because cancer evolves as it grows, it can acquire more genomic complexity over time. DNA sequencing and RNA expression levels in tumor and normal tissues will help guide care by analyzing the patient’s cancer genomic abnormalities to determine the specific changes that have occurred. A multi-drug combination has the potential to treat lung cancer by blocking multiple cancer pathways that develop as a result of these genomic changes.

For the most effective results, researchers work to pair the drug combinations that may work best to combat each lung cancer genomic abnormality. To accomplish this, WIN developed an algorithm, SIMS (Simplified Interventional Mapping System), which is hypothesized to better predict personalized treatment for cancer patients.

The end goal is to pair every lung cancer genomic abnormality with an effective drug combination. This may lead to dozens of clinical trials aimed at accomplishing this goal. In the future, this treatment algorithm could potentially be expanded to other tumor types such as colon or breast cancer.

The SPRING trial will be led by Razelle Kurzrock, MD, (University of California San Diego, Moores Cancer Center) and co-led by Enriqueta Felip, MD, (Vall d'Hebron Institute of Oncology). It will be launched in five countries and eight WIN member sites. Avera, one of two sites in the U.S., is the first to begin enrolling patients.

The SPRING trial will be conducted in two phases. Phase I will explore the safety of the drug combination and determine the optimal doses for Phase II, which will explore the efficacy of this tri-therapy regimen in first-line treatment of metastatic non-small cell lung cancer. The trial will have strict eligibility criteria and limited enrollment.

About Avera Health

Avera Health is an integrated health system comprised of more than 330 locations in 100 communities in a five-state region. A full continuum of care is offered through 32 hospitals, 200+ clinics, retirement communities, home care, sports and fitness centers, with award-winning care in 60+ medical specialties. With more than 17,000 employees and physicians, Avera is the largest private employer in South Dakota. Avera is distinguished through technology and innovation. We are home to the world’s most extensive telemedicine network, and a world-class genomics program that translates the latest cancer research directly to patient care. As a health care ministry, we carry on the legacy of the Benedictine and Presentation Sisters, delivering care in an environment guided by our values of compassion, hospitality and stewardship. For more information about Avera, see our website at Avera.org

About the WIN Consortium

Founded in 2010, WIN is unique structurally in that it brings together organizations from academia, business and not-for-profits to focus on translating the latest advances in personalized cancer medicine into the standard of care. WIN is built on the recognition that all stakeholders in personalized cancer therapy must collaborate and share information, in order to effectively bring the latest innovations in personalized cancer care to the patient. WIN is a non-profit organization formed by 40 renowned members: Academic cancer centers (32 centers in 17 countries), companies (Pfizer, Merck KgaA, Covance, Illumina, HTG Molecular, Blue Cross Blue Shield Association, etc.), non-profit organizations such as Fondation ARC, European Cancer Patient Coalition, SurviveIt. The SPRING trial will be presented during the WIN Symposium “WINning the War against Cancer” in Paris (France) on June 25-26, 2018. For further information, please visit www.winconsortium.org and www.winsymposium.org.
When my son died of cancer I decided to wage war on the disease myself
Friday, November 10, 2017
LONDON, UK (The Independent Digital Newspaper)

This story begins when my son was diagnosed with cancer at the age of eight. Like most patients who are lucky to be in an international city, he received nine consecutive lines of treatment, one after another, prescribed in the exact order of “cancer textbooks”: from nasty chemotherapy to sophisticated targeted drugs.

Were these drugs the right match for the tumour of my child? No, they were just thrown at him in a blind manner, hoping for the best.

The worst happened - my son Gaspard died.

I kept asking myself how cancer could remain a fatality in an era when the human genome – our genetic code – has been deciphered and can be manipulated to cure rare diseases; when AIDS is under control; when cars do not need drivers; and man is conquering space?

Here started my personal war against cancer. I had no strategy, no troops, no weapons to face the enemy, only my grief and determination to make things change.

Yet I knew change was needed. Treatment options have not really varied for years; research silos remain unbreakable; the costs of treatment are exorbitant; and advances in genomic-based treatment of cancer are unacceptably slow.

And so it came to pass that a year after my son’s death, in October 2010, a small group of prominent oncologists established a global collaboration of cancer centres, drug makers, technology and insurance companies built on refusal of the status quo. The network was ambitiously named the Worldwide Innovative Networking (WIN) Consortium in personalised cancer medicine, and I soon joined as director of operations.

The good news when it comes to cancer is that some important breakthroughs have been achieved recently with the introduction of targeted and immune drugs. Indeed, evidence is building in clinical trials, research and case reports to suggest that patient outcomes are improved when a specific targeted medicine can be matched to an identified anomaly of the tumour’s DNA (a “genomic aberration”).

However, the bad news is that in the majority of cases, this does not work or it works only briefly. Not all advanced solid tumours harbour potentially “actionable” genomic anomalies that can be treated with a targeted therapy. So far the approach has benefited only a small portion of patients, for a variety of confounding factors. We lack tools to understand which DNA anomaly is important versus not important, we have difficulties to predict whether a drug that targets an identified anomaly will be effective in terms of patient’s outcome. In other words we still do not know how to match a patient’s cancer to the right drug.

Even those cancer patients who are “lucky enough” to have a tumour harbouring an anomaly that can be treated with a targeted therapy, are almost guaranteed to relapse once the disease develops resistance.

In the meantime the statistics are staggering. 14 million new cancer cases are registered every year. By 2030, the global burden is expected to grow to 21.7 million new cancer cases. This means that cancer will affect everyone in the world, sooner or later, directly or indirectly. The ‘emperor of all maladies’ already claims 8.8 million deaths per year, making cancer a leading cause of death worldwide, with lung cancer being the top killer.

Lung cancer develops silently and when the first clinical symptoms appear, it is often too late - the patient is already in an advanced stage of the disease that is then incurable.

Over the past 50 years lung cancer treatment has been largely ineffective. As Dr. Razelle Kurzrock, senior deputy director for clinical science at UCSD's Moores Cancer Center and Head of WIN Clinical Trials Committee, said in a recent interview: "we were blindly throwing drugs at [patients] hoping something will stick".

Around 14 per cent of non-small cell lung cancer (NSCLC) patients with stage IIIA disease survive five years after diagnosis; with stage IIIB disease the five-year survival rate is only 5 per cent. When the disease has spread to other parts of the body, the five-year survival rate drops to 1 per cent. Unfortunately 60% of patients are diagnosed at late stage IV.

With the current path of drug and biomarker development, it will take decades to achieve significant improvement in cancer outcomes. Personalised oncology, aimed at giving the right treatment to each patient, is therefore a long and winding road that has left many patients on the side.

Strategy

Cancer is complex and pernicious, yet it does not develop in vacuum, but rather in an individual. Precisely because cancer is so complex, giving patients one targeted therapy does not make much biological sense. It may produce response in some patients, but responders will inevitably develop resistance and succumb to the disease. It is time to look at patients as individuals and to develop combination treatments, or ‘cocktails’. But how can we determine personalised therapy combinations that can be used to treat lung cancer, or other deadly malignancies? There is no clear answer yet.

The easiest way to cure cancer is to prevent it. Global tobacco control is critical to achieve this goal. When lung cancer is detected at an early stage, surgery and adjuvant therapies are enough to achieve cure. But what if the patient arrives too late, having an advanced form of the disease? How can we deliver the gift of time and quality of life that my son was denied? The strategy here resides in switching from the current monotherapy rule given in consecutive lines, towards the rational combination(s) of targeted drugs. But how many drugs do we need to combine together?

There are many trials under way exploring combinations of two drugs. With few exceptions they do not yet achieve the goal of prolonging life significantly. Patients and their families are expecting more than only a few additional weeks or months of life.

The strategy for lung cancer treatment and all other solid tumours has to be multiple modalities and multiple drugs that are optimized for each individual. Like in any war we need a strategy adjusted to the enemy who is shrewd, mutable and agile.

Our research team hypothesised that three targeted therapies with different modes of action, hitting different biological pathways simultaneously, will overwhelm cancer. This strategy is expected to achieve what targeted single agents have failed to do so far in precision oncology, especially in lung cancer — stave off cancer resistance and prolong long-term survival. The triple-therapy hypothesis is that all patients could be treated in a personalised way (and not only a minority whose tumour harbours a known targetable DNA anomaly), and that the patient outcomes would be significantly improved. Indeed, the strategy has been successfully implemented in patients with AIDS, whose viral load is effectively controlled with triple-therapy thus reducing AIDS to a chronic disease.

However, cancer is far more complex than AIDS, and one triple-therapy will not fit all lung cancer patients. The pathways that cancer uses to thrive are many more than we thought before, propelling us to conclude that patients will need several tri-therapy combinations to fight cancer.

Tactics

Two innovative tactics and weapons were developed to make this tri-therapy approach possible. First, three drugs were selected among those already existing on the market; second, an algorithm based on a new biomarker technology was put in place. The latter explores a broad spectrum of analyses that ‘imprint’ the disease, a routine procedure even in the most advanced clinical trials. They include the investigation of the tumour DNA but also the gene expression of the tumour tissue in comparison to the healthy tissue of the patient.

The algorithm is able to integrate billions of bytes of data with the purpose of identifying meaningful individual biological anomalies or pathways that can be targeted with a ‘cocktail’. In terms of military strategy and tactics, the objective being pursued is to ‘hit them (the relevant pathways) where it hurts’.

This novel strategy is ready to be tested. The US Food and Drug Administration (FDA) has already given its blessing to the launch of a unique WIN Consortium trial in first line therapy (that is for non-treated patients) of metastatic NSCLC.

While the first proof of concept trial is getting off the ground with the first tri-therapy, a second combination is coming. The more tri-therapy combinations are studied, the faster we obtain more options for patients and elucidate the ability of the algorithm to match patients to the right combinations. With more than one therapeutic option, patients will be able to switch to different combinations as resistance emerges and extend survival for many more years than is currently possible.

One could say that this is a nice strategy but still a hypothesis until proven by clinical trials. The major risk here is losing time – to be too late for those who wait for a miracle. For the sake of the patients, we cannot afford to wait for the results of the first tri-therapy trial before we move to the next. My dream is to have within 5 years clear answers and build substantial knowledge to make a quantum jump in treating lung cancer patients who have been left without significant survival improvement for the past 50 years.

We need many more strategies to win the war against cancer, apart from research intuition and foresight. Tough political battles lie ahead of us: we have to convince drug developers to collaborate; we will need ambassadors and supporters to convey our message; we have to persuade governments to help. We are all at war against a common enemy.

Catherine Bresson is Director, Operational Team of the WIN Consortium