Could genetic testing unlock treatments for Cancer of Unknown Primary?

Could genetic testing unlock treatments for Cancer of Unknown Primary?

World CUP Week: Researchers are screening hundreds of tumour genes in search of drug targets that could open the door to more personalised cancer care

Most cancers are named – and treated – according to where the first tumour is found. But for some patients, tumours are detected in various organs of the body but the origin of the disease remains a mystery. 

People with Cancer of Unknown Primary (CUP) are up against it. Their disease is advanced at the time of diagnosis and there are no specific treatment options available. As time is of the essence, they are usually offered several drugs at once – an approach known as polychemotherapy – in the hope that one of them may work. The outcomes are often poor and therapies affecting all of the body’s cells can make patients feel very unwell. 

‘We would like to see a more personalised approach to therapy in patients with CUP,’ explained Dr Manel Esteller, Director of the Josep Carreras Leukaemia Research Institute (IJC) in Barcelona. ‘For common cancer types, such as colon cancer and lung cancer, some hospitals screen patients for genes which help them select a targeted therapy. In CUP, we don’t yet know which genes to look for.’

To rectify this, Dr Esteller is running the CUPP-On project which will analyse samples from 50 patients with CUP. The team are looking for up to 500 genetic mutations or copy number variations (CNV) frequently observed in solid tumours, for which there are already approved therapies available. 

‘In selected cases, we will take a sample of the patient’s tumour and grow it in mice where we can then test existing therapies to establish whether it reduces tumour growth,’ Dr Esteller said. 

Clinicians may consider using this information to change their patients’ treatment plan. Looking at the bigger picture, the study could offer clues about the origins of CUPs. ‘Is the original tumour small or hidden? Is there something special about these tumour types? Are certain genes responsible for a proportion of CUP cases? We hope to find out,’ said Dr Esteller. 

Other advances could flow from the project, such as the inclusion of CUP patients in so-called basket trials where patients are recruited to clinical studies based on having a tumour with a specific mutation which can be targeted by a drug. 

‘Basket trials don’t care about tumour type or location – they include patients based on the presence of certain mutations,’ Dr Esteller said. ‘If we show that some CUP patients have mutations that are actionable by a drug, it becomes possible to join these kinds of trials.’

He said targeted therapy also brings benefits beyond survival as treatment tends to be well tolerated, helping to preserve quality of life. If the study proves successful, the results could be translated into clinical practice relatively swiftly as the drugs are already approved for human use. What’s more, as the cost of gene sequencing is much lower than it was a decade ago, there are fewer barriers to access in hospitals with sufficient lab capacity. 

The CUP-On project is supported by the Sarah Jennifer Knott Foundation, a charitable organisation devoted to promoting awareness, education and research of CUP. ‘Support from charitable foundations is critical right now as it can be challenging to attract large grants from public agencies for rare tumours,’ Dr Esteller said. ‘Foundations can make a big difference by jump-starting research initiatives like this one.’

Tanya Knott, Director of the Sarah Jennifer Knott Foundation said patients diagnosed with cancer of unknown primary desperately need greater access to genomic profiling and potential targeted treatments. ‘The potential diagnostic and treatment opportunities that Dr Esteller’s research study will bring for CUP patients is incredible and we feel honoured to contribute to his amazing work.’

 World CUP Awareness Week runs from 20-26 September 2021

“We’re at a critical moment for precision medicine in cancer care”

“We’re at a critical moment for precision medicine in cancer care”

Cancer will only be beaten when the genomic drivers of a person’s cancer are understood and targeted, according to Brian Tomlinson of Foundation Medicine

Tell me about yourself and your organization

Brian Tomlinson – Medicine Foundation

Foundation Medicine is a molecular information company dedicated to transforming cancer care through a deep understanding of the genomic changes that contribute to each patient’s unique cancer. The company offers a full suite of comprehensive genomic profiling assays to identify the molecular alterations in a patient’s cancer and match them with relevant targeted therapies, immunotherapies and clinical trials.

I joined Foundation Medicine after working for two national cancer patient advocacy  Organizations for nearly 18 years. In my role at Foundation Medicine, I lead our external engagement efforts with our patient advocacy partners in the US.

What does personalized medicine mean to you?

Personalized medicine involves providing treatment based on the unique drivers of disease at a molecular level. In cancer, this starts with comprehensive genomic testing to understand what’s driving a patient’s cancer at a molecular level. This gives oncologists and patients the information they need to make informed treatment decisions.

We’re at a critical moment for precision medicine in cancer care. To me, it means finding the right treatment, for the right patient and the right time.

Why do you believe this topic is important? 

I am motivated every day by the patients we serve now and the opportunity we have to impact cancer care in the future. Unfortunately, many patients right now do not have access to genomic testing. We have an opportunity to extend lives or even manage cancer as a chronic condition for certain patients today using these breakthrough therapies, but we can only do this when physicians understand the genomic drivers of a patients’ cancer.

As part of our efforts to expand access to genomic testing, we engage with advocacy groups and patients across indications to share scientific insights and serve as a resource on CGP with the goal of expanding overall education and awareness. I have dedicated my career to supporting cancer patients and their families. Having comprehensive testing provides access to really important information about treatment planning and shared decision making.

Why is your organization interested in participating in this multi-stakeholder collaboration? What has your organization been doing in this space?

We believe that transforming cancer care and ensuring all patients can benefit from precision medicine cannot be done alone, which is why we believe collaboration across the ecosystem is so critical. Over the past almost 10 years we’ve established deep partnerships with organizations across academia, industry, biopharma and advocacy.

What makes this collaboration unique?

I think the global focus and the comprehensive external stakeholder engagement make this collaboration a first of its kind and quite unique.

What are your ultimate expectations from the project?

We know expanding access to CGP is critical to increasing the number of patients who can benefit from precision medicine. We’re committed to working across the ecosystem to ensure all patients can benefit from the latest science at the time of care and that oncologists have the tools to make informed treatment decisions. We’re at a true turning point for precision medicine in many regions – including Europe. The healthcare ecosystem has made incredible progress in recent years but there is more work to be done.

‘We need truly collaborative initiatives like this’

‘We need truly collaborative initiatives like this’

Begonya Nafria Escalera of Sant Joan de Déu Children’s Hospital in Barcelona has both a professional and personal interest in ensuring that patients’ needs are met by personalized medicine

Tell me about yourself and your organization

Begonya Nafria Escalera – Sant Joan de Déu Research Foundation

I’m working at Sant Joan de Déu Children’s Hospital as Patient Engagement in Research Coordinator. My area of responsibility is to ensure that the patients and families have an active role, as experts, in any of the research and innovation projects in which our institution is involved. Sant Joan de Déu Children’s Hospital is the largest paediatric hospital in Spain. My background is in social sciences and working in the defence of the patients’ rights for more than 10 years. Also I have a personal story linked with my area of expertise, as I’m caregiver of an adult with cerebral palsy, my brother. In recent years I have also been volunteering with several patient organizations.

What does personalized medicine mean to you? 

For me it means the opportunity to offer a treatment for a huge group of complex conditions, the genetic diseases. Most of these conditions affect paediatric patients and there is no cure for them, only in some cases palliative treatments. PM from the patient side means hope but also uncertainty. At this moment, few conditions have the opportunity of these innovative treatments, this means that we need to inform and educate the patients/families about this type of treatment, how it works and what it means to be involved in a clinical trial.

Why do you believe this topic is important? 

Because research in new treatments is moving to this direction: try to provide the best and most accurate treatment for the patients. Society and specifically the patients/caregivers need also to move in this direction, knowing what a therapy means, when it works and also the status of research according to the different genetic conditions.

Why is your organization interested in participating in this multi-stakeholder collaboration? 

We are increasing our activity in the field of clinical trials in paediatric conditions, as most of these diseases are genetic. For our patients this really can be an opportunity for treatment in the future, considering that probably at the present we don’t have therapeutic options to offer to them. In parallel, in our institution the research model is based on a patient-centric approach, ensuring that in any project in which our institution will be involved patients/families can take part as advisors and/or part of the research team. We have a young person’s advisory group helping in many projects, a board of parents, and according to the needs of every initiative we set up a specific group of patients/parents to help in the design and development of the project. We don’t envision clinical research without the involvement of patients and parents.

What makes this collaboration unique? 

For me, it’s the 360 degree approach with a pillar being patient involvement and the issues that need to be addressed to ensure the best quality of life, disease management and empowerment. The activities around health literacy are essential to ensure that any initiative about personalized medicine will be patient-centric, providing patients with the right information to make decisions about their health and treatments.

What are your ultimate expectations from the project? 

I am happy to contribute to a global initiative in which patient engagement will be an essential part of the framework, while increasing awareness about health literacy in this field and providing the expertise of working with paediatric patients. As clinical trials in children and young people are global, we need truly collaborative initiatives involving different stakeholders in order to provide the best treatments for the patients, always considering the unmet and specific needs of the most vulnerable groups of patients.

‘I am on a mission to fix that’

‘I am on a mission to fix that’

Susan McClure, founder and CEO of Genome Creative, says that while clinical adoption of targeted treatments remains low, multi-stakeholder efforts such as FT3 can change this

Susan McClure – Genome Creative

Tell us more about your organization

We specialize in content strategy, editorial and design updates, event creation and management, websites, podcasts, apps, and marketing. Specifically, we work with partners who share our vision of educating people around how their treatment options are changing thanks to our increased understanding of our DNA. Our goal is to educate people around this exciting time in health care while dispelling myths, explaining the science, and encouraging further exploration.

Genome Creative specializes in creating compelling content that explains complicated topics in a language that everyone can understand. Our team of award-winning science writers and health care journalists are adept at covering this emerging field in a way that is engaging and accessible.

What does personalized medicine mean to you? 

I’ve been leading consumer health media companies since 2003, after recovering from an aggressive form of breast cancer. I spent a decade as the publisher of CURE magazine. During my time there, I realized that treatment options were becoming more targeted but clinical adoption and consumer awareness remained low. I am on a mission to fix that. 

I left CURE in late 2012 to launch the first national consumer magazine exclusively devoted to genomics. Genome magazine launched in 2014 with the mission of exploring the world of personalized medicine and the genomic revolution that makes it possible, empowering readers to make informed health decisions by improving their health literacy. 

While doing research for the business plan, I was truly shocked to see how many treatments that are considered the “standard of care” for conditions like depression, cancer, and Alzheimer’s are ineffective for many patients. Can you imagine if the same standards applied to the auto industry for example? Just imagine how upset you’d be if you paid $70,000 for a car that only ran 25 to 30 percent of the time! We need to demand more of our health care system. 

Why is your organization interested in participating in this multi-stakeholder collaboration? What has your organization been doing in this space?

While I am a huge advocate for personalized medicine, I understand the complexities that exist in terms of adoption. I believe that the only way to break down barriers is to bring together a diverse set of stakeholders who are committed to improving access to testing and targeted treatments for any patient who may benefit. My team already works with clients on communication strategies that educate patients about the ways testing and treatment for a variety of conditions are becoming more targeted. We also direct patients to useful resources so they are better equipped to have meaningful conversations with their HCPs about more personalized treatment options.

What makes this collaboration unique?

I believe that this is the first and only global coalition to address this issue by bringing patients, advocates, pharma and diagnostic companies, HCPs, payers, and regulators who will all work together to establish best practices to make personalized care accessible to all people.

What are your ultimate expectations from the project?

My hope is that no matter where a person lives in the world, when faced with a health challenge that could benefit from testing and treatments tailored to the unique characteristics of their disease, they will have easy access to education, information, and support that will enable them to make better health decisions with improved outcomes.

‘True personalized medicine should be the goal’

‘True personalized medicine should be the goal’

Danielle Barron speaks to FT3 board member Dr. Benedikt Westphalen, Head of Molecular Diagnostics and Therapy Program and the Molecular Tumour Board, Comprehensive Cancer Centre, University Munich, Germany

Dr Benedikt Westphalen is a medical oncologist and molecular biologist, focusing on gastrointestinal oncology and precision oncology. For the last four years, he has been building a precision oncology program at the University of Munich. 

Oncology has been transformed in recent years by the concept of personalized medicine. Westphalen explains that, in his field, personalized medicine covers “multiple aspects”. 

“The most comprehensive statement would be ‘the right treatment, for the patient at the right time’,” he says. “This covers all aspects from assessing the patient’s prevalence, working with a multidisciplinary team to design and discuss a personalized treatment plan to then realize this plan together with the patient.”

Unsurprisingly, Dr Westphalen is of the belief that personalized medicine should not be a “nice to have”, but rather an essential approach to patient care. In this setting, it is important “to have all necessary tools at hand” to offer patients the most comprehensive oncological care, Westphalen states. 

“True personalized medicine, going beyond only focusing on certain aspects in the continuum of oncological care, should be the goal of every practicing oncologist to achieve the best outcome for every individual patient,” he states.

As a healthcare professional and research scientist, Westphalen practices personalized medicine every day. But he believes that the multi-stakeholder collaboration involved in the FT3 project will bring it to the next level.

“FT3 covers an important aspect in personalized medicine, namely the interplay between comprehensive biomarker testing and treatment decisions based on the individual profile of a patient’s tumor. Modern oncology increasingly depends on this interplay.”

Yet, there are still many roadblocks in place, which prevent caregivers from offering both modern tumor testing and innovative targeted agents to their patients. We can only overcome these roadblocks by working together in a dedicated team, he adds. To this end, he has great faith in the objectives of the FT3.

“This multi-stakeholder non-profit initiative has a strong focus on patients’ needs and strong backing within industry, this makes for a very good start to create sustainable projects and ultimately lasting value”. 

While Dr Westphalen has been working in personalized medicine for a couple of years, he is still very excited about the potential of the FT3 project.

“I hope that we will be able to form a group of dedicated people, growing together with the aim to drive all aspects of precision oncology ultimately improving care for our patients.”

“Every day matters”: What it means to have a rare disease

“Every day matters”: What it means to have a rare disease

Patients with rare disease often do not have a voice and rely on strong support from family, carers and trusted advocates. On Rare Disease Day 2021, FT3 speaks to advocates for those with a rare disease, who outline the barriers and roadblocks to obtaining a prompt diagnosis and the best possible personalized treatment.

Warnyta Minnaard is the co-founder of Missie Tumor Onbekend, the patient support and advocacy organization for patients with cancer of unknown primary (CUP) in the Netherlands. 

Cancer of unknown primary is the fourth most common metastatic cancer in the Netherlands, with about 1,400 Dutch people each year diagnosed with CUP. Missie Tumor Onbekend advocates for a specialized diagnostic and care pathway for CUP patients, better access to innovative diagnostics and (curative/palliative) care. Furthermore, we provide support to patients, share information about CUP, raise awareness and support clinical research to try to find a solution for CUP.

About 2.5 years ago my partner Hederik (age 32) suddenly became ill. It all started with a hanging eyelid and we started with a journey in the hospital to try to find out what was wrong. Unfortunately, he passed away in early January 2019 and I became a widow at age 29. Even though he was severely ill, we had no idea he was going to die as we were in the midst of an ongoing diagnostic trajectory that already took seven months. This is more often the case with a CUP diagnosis; you don’t understand that it is a diagnosis to have cancer without knowing the origins. 

Patients with CUP are an outlier in the oncology community, as they are metastatic cancer patients but the origin of their disease is unknown and therefore unfortunately their chances towards accessing treatments is still rather limited. You would expect an outlier to be uncommon, but CUP is the eighth most common cancer in the world; because this is such a diverse group of patients, it is challenging to provide a single solution. But it is clear, these patients deserve solutions; it is unbearable to be part of a patient group without evening knowing you are part of the group as your diagnosis is cancer of unknown primary and if nothing is done you will not survive. Furthermore, most cancer therapies are based on the origin of the disease, which is exactly unknown for CUP patients. More than half of CUP patients in the Netherlands pass away in less than two months, so urgency is needed.

I believe the focus should be on improving or changing diagnostics so that there is no longer a strict need to know the localization of the tumor, rather the DNA defects of the tumor cells of the metastases found in the body should become clear. So that treatment can be provided on the basis of molecular patterns and patients get an outlook and a chance towards care instead of staying in a diagnostic trajectory with no end. The developments of personalized diagnostics and treatments are exactly what CUP patients are in dire need of.

Susi Vander Wyk is executive director of Cure SMA Canada

Spinal Muscular Atrophy (SMA) is a motor neuron disease. The motor neurons affect the voluntary muscles that are used for activities such as crawling, walking, head and neck control, and swallowing. It is a relatively common “rare disorder”; approximately one in 6,000 babies born are affected, and about 1 in 40 people are genetic carriers.

SMA affects muscles throughout the body, although the proximal muscles (those closest to the trunk of one’s body – i.e. shoulders, hips, and back) are often most severely affected. Weakness in the legs is generally greater than in the arms. Sometimes feeding and swallowing can be affected. Involvement of respiratory muscles (muscles involved in breathing and coughing) can lead to an increased tendency for pneumonia and other lung problems.

Until very recently, there have been no treatments available for SMA patients. At diagnoses, they were simply told to take their children home and love them for as long as they had them.  We at Cure SMA Canada offered support for newly diagnosed families, through life and in the event of end of life, we are there as well. We advocated for access to the first treatment that came available for SMA patients and were successful to receive approval in Canada.  Unfortunately it wasn’t approved for all patients. 

Every stepping stone along the path in the Canadian approval process was faced with barriers and the need for strong advocacy to justify patient access to the only treatment for SMA. The unfortunate loss of life and function during this process was devastating.  With a progressive disease such as SMA, every day matters, every day is a loss of function and fear of what the future holds without treatment.  We are now in the process of advocating for two new treatments here in Canada, we still have patients not accessing treatment because they fall outside the criteria for these treatments and we are advocating from square one again, justifying and waiting for approval while our patients continue to experience loss of function and experience high anxiety waiting to hear if the federal and provincial governments makes their life and death decisions. When you have a progressive disease, and are experiencing loss of physical abilities, it is even more devastating to know that other jurisdictions are approving treatment.  In the meantime, we continue our work, to fight for our patient’s right to live their best life, to justify a life with treatment and hope that we are heard and considered partners in the decisions that will impact quality and quantity of life. Until we have a cure for SMA, the need for new and improved treatments will continue. Clearly involvement in clinical trials is essential for this information to be developed and available for Canadians.  We must be participants and not bystanders.