The government hopes genome sequencing technology will improve the treatment of cancer
A series of NHS and healthcare events are taking place over the coming weeks to spark a conversation among healthcare professionals about genomics.
They will help educate healthcare professionals about the benefits of genomics – the practice of using people’s DNA and genetic information to inform their clinical care – in improving diagnosis and treatment for patients.
Health Education England (HEE) held its second annual #GenomicsConversation this week to increase health professionals’ familiarity about genomics. HEE’s campaign involves panel events, online courses, the launch of new podcasts and educational resources.
In December last year, health secretary Matt Hancock announced that the 100,000 Genomes Project, led by Genomics England in partnership with NHS England, reached its goal of sequencing 100,000 whole genomes from NHS patients.
The programme was launched in 2012 by then prime minister David Cameron, with the goal of harnessing whole genome sequencing technology to improve diagnosis and treatments for people with rare inherited diseases and cancer. The project laid the foundations for a NHS Genomic Medicine Service, which will provide genomic testing to patients across the NHS from 2019.
HEE wants to make healthcare professionals aware of the roll-out of the new service and whole genome sequencing so that they feel more comfortable discussing genomic testing with patients, and can signpost them to relevant information and services.
Meanwhile, the University of Cambridge will be holding an event on genomics on 13 March as part of Cambridge Science Festival to celebrate the sequencing of all 100,000 genomes and the UK becoming the first nation in the world to apply genome sequencing at scale in healthcare.
Genomics England interim chief executive and chief scientist Mark Caulfield said: ‘The Genomic Medicine Service is the first of its kind where genomics will be embedded into a national health system and transform routine healthcare in the UK.’
Four regional events organised by NHS England in partnership with Macmillan Cancer Support, Cancer Research UK and NHS Horizons will take place in London, Birmingham, Bristol and Leeds, starting from 12 April. Entitled Genomics and Personalisation of Cancer Care, they will explore how genomics can be embedded into personalised cancer care.
They will also enable those working in NHS Genomic Medicine Centres to engage with the public and other healthcare professionals to reflect on the transformation that has already taken place, and consider the changes that will be needed in the future.
Cancer Nursing Practice conference
Genomics will also be among the topics presented at Cancer Nursing Practice’s annual conference on 1 May, where Barts Cancer Institute and Genomics England specialty trainee and clinical research fellow in medical oncology Alison May Berner will present on the implications of genomics for people with cancer and nursing. She will also discuss some of the findings of the 100,000 Genomes Project by drawing on patient case studies.
The overall theme of the conference is patient experience. Topics include dementia and cancer, social prescribing, pain management, managing a large systemic anti-cancer therapy unit and supporting patients with recovery.
Royal Wolverhampton NHS Trust matron for oncology and haematology Doreen Black, who won the top leadership category in NHS England’s 2018 Windrush Awards, will make a keynote address.
The early bird rate for registration expires on 15 March and you can book here
Karan Jensen was diagnosed in 2017, aged 48 with cervical cancer. Karan ordered the Oncofocus Test to identify additional treatment options and shares her story here in the following Q&A.
How did your diagnosis come about?
I had been having regular smear tests, but then one came back with irregular cells and the doctor asked to see me in 6 months time. We were moving, so I delayed going back, but when I did get to the doctors, they ended up doing a biopsy. Within 2 weeks I was diagnosed with Stage 2B cervical cancer with lymph node involvement.
What happened after you were diagnosed?
Treatment was started to cure my cancer. I had four cycles of cisplatin chemotherapy plus 32 sessions of radiotherapy.
Did this treatment work?
Unfortunately, the tumour did not change with this type of chemotherapy, so I then started on carboplatin and paclitaxel.
Did the second round of treatment work?
I was meant to have six sessions of this chemotherapy, but after three, I had a scan and found out that the tumour had grown. I was told that there was no point continuing treatment as my cancer was incurable, and to go home and get things in order.
Did you experience any side effects of chemotherapy?
During chemotherapy, I was hospitalised four times with infections and neutropenic sepsis. The chemotherapy also caused swelling of my legs (lymphoedema), and my kidneys had been damaged so that I had to have a nephrostomy bag attached to collect urine.
How did you feel when they told you that you cancer was incurable?
I have an 11-year-old son, so I was not going to give up and did some research online on the best treatments for my cancer.
What did you find searching online?
I found out about the Oncofocus® cancer test by Oncologica on their website and got in touch.
Was it easy getting the Oncofocus test done?
It cost £2000 but it was an easy decision to make. I just had to fill in a few forms and Oncologica did all the work to get the biopsy from my hospital.
What were the results of the Oncofocus test?
The test quickly came back that my tumour was exceptionally high in a protein called PD-L1, so it would respond really well to immunotherapy, which works by boosting a person’s immune system to help it recognise and fight cancer cells.
What happened when you knew the results of the test?
The treatment that the test recommended was not available on the NHS so my oncologist contacted Christie Hospital in Manchester, which was part of the PROCLAIM-CX-072 clinical trial that is investigating an experimental drug that targets PD-L1.
I was very sick at this stage, and the doctors were not sure that I would be well enough to get into the trial. As my levels of PD-L1 were so high, however, they thought they had to give me the opportunity.
Was this new treatment successful?
I was meant to have four sessions of CX-072 plus ipilumumab every 3 weeks, plus CX-072 maintenance therapy for a year. Although the treatment was not as bad as chemotherapy and I did not lose any hair, it still made me feel very poorly. After the third session, I developed a bad reaction and the level of some of my white blood cells that fight infection, neutrophils, plummeted and could not be restored to normal. It was therefore too risky to continue the treatment.
The good news was that a scan in March this year showed that the new therapy had reduced the tumour by 50%.
Are you still receiving treatment?
Even though the treatment has stopped, my immune system has taken over and is fighting the tumour. I am scanned every 2 months, and every time my tumour reduces by a further 0.5% to 1%. Last week I had another scan, and it had reduced by 3% and I feel better today than I have over the past 3 years.
What are your thoughts on the Oncofocus test?
If I had had the test before receiving chemotherapy, this would have saved the NHS a load of money giving me a treatment that did not work and putting me through so much. I continue to need a nephrostomy bag due to the damage done by chemotherapy, which needs changing once a week and the tubes replaced in hospital every 3 months.
What is happening now?
We are now at the ‘watch and wait’ stage. However, as I have had such a good response to the immunotherapy and feel so much better, I can have more treatment if needed in the future. The swelling in my leg has gone down and I can now wear my shoes and move around normally again. I was so sick that I did not think that I would see last Christmas. Now I will get to experience Christmas again this year.
A “revolutionary” new class of cancer drug that can treat a wide range of tumours has been approved for use in Europe for the first time. Tumour-agnostic drugs do not care where the cancer is growing in the body as long as it has a specific genetic abnormality inside. UK doctors testing the drugs said they were “a really exciting thing”.
They said the approach had the potential to cure more patients and cut side-effects. The drug that has been approved is called larotrectinib. Charlotte Stevenson, a two-year-old from Belfast, was one of the first patients to benefit.
She was diagnosed with infantile fibrosarcoma, a cancer of the body’s connective tissue. She has been treated with larotrectinib as part of a clinical trial at the Royal Marsden Sutton, in London, for the past year. Her mum, Esther, said: “We knew that our options were limited [so] we decided to give it a try and are so glad that we did.
“We have been able to watch Charlotte develop and grow at a rapid rate, making up for lost time in so many ways and amazing us all with her energy and enthusiasm for life.
“She can now have a relatively normal life and, best of all, the drug has had an incredible impact on the tumour.”
Charlotte’s tumour was caused by a genetic abnormality known as an NTRK gene fusion.
One part of her DNA accidentally merged with another and the alteration in the blueprint for her body led to the growth of her cancer.
But NTRK gene fusions are not unique to sarcomas – they also appear in some brain, kidney, thyroid and other cancers.
“It is a really exciting thing, as is it works across a range of cancers. It’s not confined to one,” Dr Julia Chisholm, a children’s cancer consultant at the Royal Marsden Hospital, told the BBC.
NTRK mutations are relatively rare, but other targeted therapies are in development.
It marks a move away from treating a “breast cancer” or “bowel cancer” or a “lung cancer” and towards precision medicine that takes advantage of the genetic make-up of each patient’s tumour.
Dr Chisholm told the BBC: “The beauty is it targets the abnormality.
“There are a number of biochemical pathways that are common in many different tumour types.
“I think this is the way things are going and this is about better outcomes, curing more patients and producing kinder treatments with reduced side-effects.”
The decision by European regulators does not mean it will be instantly available for patients in the UK. But earlier this year, NHS England described tumour-agnostic drugs as a “revolutionary” and “exciting new breakthrough” in cancer and said preparations were under way to ensure patients were given access to them.
“The benefits for patients – in particular children – of being able to treat many different types of cancers with one drug is potentially huge, helping them to lead longer, healthier lives,” NHS England chief executive Simon Stevens said at the time.
Prof Charles Swanton, Cancer Research UK’s chief clinician, said the drugs were “exciting”. He added: “The NHS will need to ensure the right genomic testing is available across the country to identify patients who could benefit so it’s good that the NHS is already thinking about how to get this to patients with cancer as soon as possible.”
Dr Brendon Gray, from Bayer, the drug company that developed larotrectinib, said: “As the first tumour-agnostic medicine approved in Europe, larotrectinib represents a real shift in cancer treatment.”
Molecular genetic testing identified the most precise treatments
Genetic testing not only provides information regarding the chance of developing a particular disease but is also crucial in identifying the most effective anti-cancer therapy for each individual patient suffering from any solid tumour. Thus the battle against the tumour is tailored.
Genetic tests are basically of two types: the first is the predictive one, which allows asymptomatic people to reveal all the hidden secrets of their DNA and to quantify their risks of falling ill with certain diseases, cancer in particular, especially tumours of breast and ovary, colorectal and prostate and other diseases such as juvenile Alzheimer’s and cardiovascular diseases. The second type of test is aimed at people already suffering from cancer, a precision cancer test that is able to identify the most effective cancer therapy, especially biological, for each individual patient suffering from any solid tumour. From the routine paraffin blocks containing the excised or biopsied tumour tissues of the individual patient, stored in the pathology archive of the treating hospital, a piece of this material is sent to the precision oncology laboratory, for example Oncologica UK, based in Cambridge, UK. Here the sample is analysed using the Oncofocus test and within 10 – 15 days the report is issued which provides Oncologists with the linkage between the identified genetic mutations and the targeted drugs approved by the major world organizations as well as those undergoing clinical trials and additionally the immunological drugs that have recently entered clinical practice.
There is now a major change in direction regarding the method used for treatment selection in cancer. This modern approach, rather than recommending treatments based solely on the fact that the individual has a specific type of cancer, such as lung, breast, colorectal, etc., instead bases therapy selection by examining the disease at a molecular level. The best way to treat cancer with modern anti-cancer drugs is therefore “agnostic of cancer type”, meaning regardless of the type of cancer a patient may have developed. This is an approach that has been approved by the US Food and Drug Administration (FDA) and that has been adopted by many other countries such as Australia.
These “tumour-agnostic” therapies are beginning to show promising results in the clinical setting, helping patients with a wide variety of different tumours types that have previously been difficult to treat using conventional drugs, especially those patients in second line after the failure of first line treatment. In the tumour center of the Tirelli Medical Group (www.tirellimedical.it) based in Pordenone we have already treated a hundred patients with this therapeutic strategy based on the recommendations of the American Food and Drug Administration (FDA) with often surprisingly favourable results.
Notably this is in keeping with a study recently published in the journal “Oncotarget” by a group of Stanford University in California showing that the use of therapy based on precision oncology (e.g. Oncofocus Test) improves the survival of refractory cancer patients while decreasing the costs of treatment.
Mutations that play a fundamental role in the development of neoplasms have been called “driver” mutations since they are able to confer a growth advantage in the affected cells. Approximately 350 driver genes involved in cancer development have been identified in human tumours. Investigations by massive sequencing have shown that tumours exhibit numerous mutations, most of which are not drivers but “passengers”, i.e. not involved in tumour development but randomly occurring and selected by rapid neoplastic growth.
Knowing the genetic drivers, that is those genetic alterations that are the basis of tumour cell multiplication, means that it is possible to develop precision treatments that specifically and in a completely new way address the choice of biological and immunological drugs.
At the moment, oncologists have limited information in trying to find the right anti-cancer drug for their patient. There are in fact more than 300 anti-cancer drugs and hundreds of different types of cancer, each of these also possesses different genetic mutations that respond differently to therapies, it follows that, even for a good oncologist the chances of finding an effective drug mix can be low.
The use of genetic testing of the tumour biopsy sample is able to help the oncologist in making the right choice by increasing the probability of prescribing an effective drug. Immunological therapy is also identified through this type of testing. Prof. Riccardo Dolcetti, who is a professor of oncological medicine at the University of Queensland in Australia and who has been at the Cancer Institute of Aviano for a long time, tells me that there genetic testing on the tumour tissue is done following diagnosis in the major tumour types (e.g. lung, breast, colorectal, prostate, etc.) but that they also carry out genetic testing on the tumour biopsy taken following relapse if feasible. At the Tirelli Medical Group of Pordenone we carry out genetic testing only in cases of tumoural relapse, that is in patients in whom the first line therapy has failed, even though testing could take place at diagnosis to identify the best treatment available.
Even though the clinical implementation of genetic testing is still not such as to be used in routine clinical practice, it may be in the near future according to what was recently reported in the “New England Journal of Medicine”. The first so-called tumour histology-independent treatment, that is “agnostic of cancer type” was recently recommended by the European for approval in relation to the drug called Larotrectinib. This is a drug that targets a specific genetic mutation called NTRK i.e. the gene coding for the neurotropic tyrosine kinase receptor. Larotrectinib is indicated for the treatment of all pediatric and adult solid tumours that have the NTRK mutation regardless of their tumour type, i.e. whether it is breast, lung, colon, melanoma, etc.
This drug was approved in November 2018 in the United States and is considered an example of a targeted drug that radically changes the approach to cancer treatment. The data that have been recently published in the “New England Journal of Medicine” show an overall response of 76% which is quite unusual for patients heavily pre-treated with conventional therapies who have subsequently been administered Larotrectinib. This genetic alteration can be found in lung, colon, breast, thyroid and melanoma tumours.
Prof. Umberto Tirelli
Director of Tumor Center, Chronic Fatigue, Fibromyalgia and Oxygen-Ozone Therapy,
Tirelli Medical Group Clinic of Pordenone.
Oncologist, National Tumor Institute of Aviano
Sherrie Hewson was due on stage when her phone rang with shattering news.
The Coronation Street favourite’s beloved elder brother Brett had been diagnosed with an incurable brain tumour. He was given 18 months to live. Sherrie, 68, burst into floods of tears in her dressing room.
The actress, who played stroppy hotel manager Joyce Temple-Savage in Benidorm, was about to appear in a stage version of the ITV sitcom.
In the months that followed Sherrie would turn her life upside down to help Brett fight the killer disease and to be by his side.
She said: “I wouldn’t take it in. I think it was my way of dealing with it because I knew I was due on stage and because I just didn’t want to believe it.
“Brett is my big brother who I have always looked up to and he has always led a charmed life.
“Everything he touched had turned to gold and suddenly I was hearing this. It didn’t make sense.
“Part of me wanted to throw everything up in the air and go to him there and then. But another voice in my head said, ‘No. You need to keep on earning, girl, because Brett is going to need you now.’ You’d better get out here and do your job.”
Sherrie, who first trod the boards aged four, wiped aways the tears and got ready for the show at Belfast’s Grand Opera House. Fellow actors Tony Maudsley, who plays Kenneth, and Jake Canuso, who is Mateo, helped Sherrie through the show.
Sherrie said: “Not a soul in the audience knew what I was going through. Every part of me wanted to be with Brett but I had to stay strong.” That night her performance brought the house down and, despite all the heartache in the following months, Sherrie did not miss a show.
After taking her bow she dashed to Belfast airport to be by Brett’s side. On April 4, just a few days after the diagnosis, Brett, 71, was admitted to the Walton Centre, a neurological hospital in Liverpool, where a golf ball sized tumour was removed from his brain in a nine-hour operation. His daughter Chloe, 37, had insisted former DJ, male model and TV actor Brett have a check-up after his tongue stopped moving properly.
He was also sensing mysterious powerful odours and was constantly feeling tired.
At an A&E near his home in Llandudno, Conwy – where he runs a tea shop with his wife of 40 years Annie, 68, – a scan revealed a massive swelling on the brain.
Fluid had built up and Brett would have died within days without surgery.
The operation was a success but three days later he suffered a massive bleed on the brain and needed another four-hour op to remove a blood clot which had formed in the cavity where the tumour had been.
Again he pulled through and then faced radiotherapy and chemo in a bid to keep the aggressive cancer at bay. Tests showed the tumour was a grade 4 glioblastoma – the most common and aggressive brain tumour in adults.
Now Sherrie aims to be by Brett’s side as much as possible in the time he has left.
She has also become an ambassador of The Brain Tumour Charity to raise awareness of the symptoms and is seeking new treatments and drugs which could help prolong Brett’s life beyond 18 months.
She also has plans to rent a home in Llandudno to be near Brett and has arranged to do Christmas panto in the town so all the family will be together.
Sherrie, who was dizzy Maureen Webster in Corrie and has been a regular on Loose Women, said: “You never think it’s going to happen to you or your family but it doesn’t matter if you’re famous or not, young or old, brain tumours can affect any one.
“Brett wants to leave a legacy and he wants to raise awareness of this awful illness which can creep up on people.
“So becoming an ambassador for The Brain Tumour Charity was something I had to do for him and the people we may be able to help.
“I think about Brett’s prognosis every minute of the day. As a family we have vowed to live in the moment for Brett and for ourselves to get the very most out of the time we all have together with him. Fear touches everything now. It overshadows everything we do.
“I don’t allow myself to look too far into the future – it’s too frightening, so I don’t let my mind go there. He’s selfless and all he worries about is the impact on his family – that’s when he breaks down.”
Sherrie has now enlisted the help of a special medical company called Oncologica, which runs a DNA service and, after testing Brett’s tumour, has come up specifics drugs which may help him live longer.
Sherrie said: “The NHS has been amazing, they saved Brett’s life, now it is all about buying him as much time as we can.
“I’ll do everything I can to get him the very best treatment and if I have to work 365 days a year so be it. I’ll do anything.”
Sherrie, who revealed her own breast cancer scare in 2015, is aiming to raise £50,000 for The Brain Tumour Charity by offering a lunch date with herself on the good causes website Rafful – as well as an overnight stay in a London hotel for the winner.
Meanwhile her family is doing all it can to support Brett, who said his little sister and the rest of his family have been “amazing”. He said: “Sherrie and I are incredibly close and I confide my feelings and fears in her – I can tell her anything.
“We’re bound together by love and humour.
“Sherrie will always be my Shez – I’ve always called her that and always will. People think there must be ‘side’ to her because she’s an actress but she’s the same lovely, down-to-earth girl she’s always been.
“She is such a loving person with a fabulous big heart and would do anything to help anyone, especially her big brother. I’ve always told my family I love them but now I tell them I love them every time I see them and hug them closer.
“I’m grateful I’ve had such a rich, full life right up to my 70s, and I feel blessed I’ve got such a loving, supportive family around me.
“Every one of them is amazing. Chloe saved my life and Annie is my rock. I don’t know what I’d do without her. I know nothing about brain tumours. When doctors told me I had a glioblastoma I asked, ‘Is that serious?’
“The answer was, ‘It doesn’t get any worse.’ When I was told it was terminal I just couldn’t take it in. It feels like it’s a story being told about someone else.
“You’re in such a heightened state of emotion and shock that you can’t process it at first. You have to face your own mortality. This is what you’ve got and it’s going to kill you in 12-18 months. I’m learning to accept it, one step at a time.
“I’m not scared or sad for myself but I am scared and sad for my family – what lies ahead of them and the grief they’ll face.
“We’re all doing our best to live in the moment.
“I have everything I want or need – my family – and I just want to spend time with them. Now it’s about living the best life I can in the time I’ve got left.”
THOUSANDS of pounds have been donated within just two days to help a young Co Donegal mother-of-five access life saving cancer treatment.
Sonya Hamilton McCloskey (35) – who is originally from St Johnston close to the Derry border but lives with husband Michael in Ballybofey – has been fighting cancer for the past two years.
The businesswoman, who gave up work to look after her children who are aged from three to 15, first thought she had pulled a muscle.
Following various treatments for the pain, it was confirmed in April this year that she had cancer. It was later discovered that the disease had spread to her pancreas, lungs and liver.
Following a number of weeks separated from her four youngest children in an oncology ward, Mrs Hamilton McCloskey was transferred to Galway Hospital last Tuesday to have a stent inserted into her liver.
Unable to undergo chemotherapy she now hopes that UK-based specialists Oncologica will be able to provide a course of treatment which will give her a “fighting chance” against her illness.
The Donegal woman’s family set up a GoFundMe page last Wednesday hoping to raise the €2,000 (£1,785) necessary to cover the cost of having biopsies sent to Oncologica for analysis.
However, nothing could have prepared them for the public reaction to her appeal. Within just two days, a massive €36,000 (£32,139) was raised through the GoFundMe page and other donations.
The family has been overwhelmed by the support shown by the public. One man alone donated €5,000 (£4,464).
In a message issued from her hospital bed in Galway, Mrs Hamilton McCloskey and her husband thanked everyone who had donated, giving her some hope.
Her parents also took to social media to thank those who have donated.
In a post on the Sonya’s Struggle Facebook page, they wrote: “From the Hamilton family we would like to thank everyone for their support in these hard times. Sonya is one that brings our family together.”
They said their daughter had a heart of gold.
“We couldn’t ask for a better daughter. Keep on fighting dear,” they said.
Mrs Hamilton McCloskey’s Gofundme page can be accessed at https://www.gofundme.com/qap9y-sonyas-battle
Medicine has always been personal to some extent – a doctor looks for the best way to help the patient sitting in front of them.
But with advances in technology, it is becoming possible to use the most unique of characteristics – our genomes – to tailor treatments for individuals.
Genomes are made up of a complete set of our DNA, including all of our genes, and are the instruction manual on how to build and maintain the 37 trillion cells in our bodies.
Any two people share more than 99% of their DNA. It’s the remaining less than 1% that makes us unique, and can affect the severity of a disease and effectiveness of treatments.
Looking at these small differences can also help us understand the best way to treat a patient for a range of diseases – from cancer and heart disease to depression.
Cancer is the most advanced area of medicine in terms of developing personalised treatments. In the UK, differences in the DNA sequence are being used by the NHS to help doctors prevent and predict cancer. For example, women with an increased risk of developing breast or ovarian cancer have been identified by screening for changes to the BRCA1 or BRCA2 genes.
Mutations in these genes increase a woman’s risk of breast cancer by four-to-eightfold and can explain why some families see many relatives with the disease. A BRCA1 mutation gives women a lifetime risk of ovarian cancer of 40-50%.
Screening has helped women make informed choices about treatment and prevention – for example, whether to have a mastectomy.
It is steps like these – splitting patients into ever smaller groups to identify the best treatments – that is taking us towards personalisation.
- ‘New era’ of personalised cancer drugs
- ‘Dismantling cancer’ reveals weak spots
- Targeted checks ‘prevent 10% of heart attacks’
For certain cancers, measuring gene activity is becoming commonplace. Gene activity is a little like the dimmer switch on a light – it can be set to low, high or anywhere in between.
Measuring this allows us to see how active a particular gene is in a tissue or cell.
In breast cancer, a test measuring the activity of 50 genes in tumours can be used to guide decisions about whether the patient will benefit from chemotherapy.
To extend this approach to other cancers, researchers are switching off all of the genes in hundreds of tumours grown in the laboratory. In doing so, scientists are looking for cancer’s weaknesses – to try to produce a detailed rule book for precision treatment.
The development of personalised medicine
- Genome sequencing is being offered in England to children with rare diseases – and has led to a change of treatment for some
- An 11-year-old became the first patient to use a leukaemia drug called CAR-T, which re-programmes the immune system to fight cancer
- The entire genetic code of women diagnosed with breast cancer is being mapped by scientists in Cambridge
- There are plans to sequence one million genomes in the UK in the next five years
The development of such techniques raises the question: how far can personalisation go?
For illnesses like heart disease, diabetes and infectious diseases, a combination of genetic, lifestyle and life events also play a part. This means that information about small differences in the DNA sequence alone will not be enough to predict susceptibility and outcome.
Measuring the activity of our genes also captures information about current stresses to the body. For example, certain genes will have a higher or lower activity depending on the type of infection.
Yuvan Thakkar, 11, is the first to receive a drug called CAR-T.
His mother, Sapna, said: ‘This new therapy is our last hope’
Looking at gene activity could also provide important clues as to how to best treat a patient.
One life-threatening illness where these techniques could help is sepsis.
It is a condition in which the immune system damages its own organs when trying to fight an infection. Anyone can develop sepsis and it kills 52,000 people each year in the UK – more than breast, bowel and prostate cancer combined. Worldwide, a third of patients who develop sepsis die.
To save lives, general antibiotics are given first to reduce the infection. A blood test is done to find out which particular bacteria have caused the sepsis, so a more targeted antibiotic can be given. But these blood tests take precious time and cannot always identify the bacterium causing the infection.
In our research, we are looking at gene activity in sepsis patients’ immune systems, to give us clues as to why different people respond in different ways.
We hope to pinpoint which part of their immune systems are not working properly – helping doctors decide how other drugs could be used.
This demonstrates how personalised medicine could be used for short-term treatment in intensive care, as well as for longer-term illnesses like cancer.
About this piece
This analysis piece was commissioned by the BBC from an expert working for an outside organisation.
Note: In order to respect the privacy of the patient, his/her identity will not be revealed.
I was diagnosed with terminal bowel cancer in March 2018. I started radiotherapy, which worked well. The tumour then started to cause a build up of fluid in my abdomen, which chemotherapy helped to reduce. However, when the first line chemotherapy stopped working after 5 months and then the second line chemotherapy failed to work at all, the fluid returned and I had two stays in hospital to help drain it.
Having exhausted standard therapy and become bedbound, I found out about the Oncofocus Test from an online search. The overall process from submitting the form to Test results was easy and rapid. The company called to talk me through the process and to explain the results of the Test, and also took care of the logistics of collecting the sample from the hospital. It turned out that I have a rare cancer mutation and was lucky to have had a response at all to the initial chemotherapy.
I had a remarkably effective and rapid response to the drugs that the Test recommended for my cancer mutation. After just 2 weeks of treatment, my abdomen returned to normal size. After 4 weeks of treatment, I was swimming, walking and fully enjoying all that life has to offer again. I am truly grateful for the significant improvement in quality of life I experienced, especially as I had no side effects from the new drugs. The extra months that this gave me meant that I had further quality time with my family and could prepare them better for life without me.
The results of a new study, underscoring the value of precision medicine in advanced sarcoma, showed that patients with heavily pretreated sarcoma who received treatment in accord with their mutational profile attained better outcomes than patients who did not (Abstract 11018). Most notably, median overall survival reached 22.1 months for patients treated with agents targeting mutations identified by genomic profiling, compared with 15.5 months for patients who received treatment unguided by genomic profiling (HR 0.70, 95% CI [0.50, 0.98]; p = 0.031).
“Drug development in sarcomas remains challenging, with few effective U.S. Food and Drug Administration–approved therapies,” lead investigator Shiraj Sen, MD, PhD, of the Sarah Cannon Research Institute, said. “Fortunately, recent genomic analyses have revealed many potentially actionable mutations across sarcoma subtypes. However, the actionability of these potential driver mutations remains unclear, and whether patients enrolled on genomically matched early-phase trials have improved outcomes over patients enrolled on nongenomically matched trials remains unknown.”
To clarify the value of genomic profiling in sarcoma, the investigators leveraged clinical data and next-generation sequencing information for 406 patients with advanced disease who were treated within phase I trials at The University of Texas MD Anderson Cancer Center over a 12-year period (2006 to 2018). Patients had received a median of three prior lines of therapy (range, 0 to 9) before being enrolled in a phase I trial, and collectively they featured a diverse array of soft tissue sarcomas (e.g., leiomyosarcoma, 16%; liposarcoma, 13%; gastrointestinal stromal tumor, 11%; and synovial sarcoma, 3%) and bone sarcomas (e.g., osteosarcoma, 8%; chondrosarcoma, 7%; and Ewing sarcoma, 6%).
Within the 406-patient cohort, 23% of patients had potentially actionable alterations identified through next-generation sequencing and were enrolled in clinical trials of genomically matched therapies. The remaining 77% of patients who participated in nongenomically matched trials served as the comparator group.
The results revealed no difference in the objective response rate for patients who were and were not matched to treatment based on their genomic profile (11% vs. 6%, respectively; odds ratio [OR] 1.97, 95% CI [0.88, 4.44]; p = 0.10). However, significant differences favoring the genomically matched group over the unmatched group were observed for the clinical benefit rate (41% vs. 19%, respectively; OR 2.91, 95% CI [1.77, 4.80]; p < 0.0001), the median time to progression (3.7 vs. 2.7; HR 0.72, 95% CI [0.57, 0.91]; p = 0.0048), and median overall survival (22.1 vs. 15.5 months; HR 0.70, 95% CI [0.50, 0.98]; p = 0.031).
“In our study, while response rates in genomically matched trials were low (11%), occasional responses were seen with experimental therapies targeting alterations such as NTRK, LRRC15, cMET, mTOR, VEGF, MDM2, and FGFR. This suggests that molecular profiling should be considered in metastatic, refractory sarcomas and clinical trial enrollment should be considered for these patients,” Dr. Sen said.
Kara Nyberg, PhD
Immunotherapy is a burgeoning sector that heralds a breakthrough against the world’s second-most deadly disease. Dr Mike Tubbs explains how investors can benefit too.
Cancer is the world’s second-biggest killer. The disease is responsible for around one in six deaths globally; 9.6 million people succumbed to it in 2018, while 18.1 million new cases were diagnosed. In 2025 there will be more than 20 million new cases, according to the World Health Organisation’s International Agency for Research on Cancer, and 29.5 million in 2040. To reduce cancer deaths we need new treatments beyond the conventional options of surgery, radiotherapy, chemotherapy and drugs discovered years ago. Fortunately, the last few years have seen a breakthrough in cancer treatments as a new field of research has developed: immunotherapy.
A new approach
Cancer immunotherapy is a new method of fighting cancer that uses the body’s own immune system to kill cancer cells where they are growing. This doesn’t happen naturally. The immune system is wired to conduct safety checks that prevent it attacking normal body cells. Cancer cells cleverly use these checks to fool the immune system into thinking tumour cells are just like normal cells – in other words, the cancer cells make themselves invisible to the body’s T-cells (white cells tasked to deal with disease carriers). That means T-cells cannot recognise cancer cells and therefore cannot attack them. The techniques of immunotherapy are all based on various ways of removing this cloak of invisibility from cancer cells and helping the immune system work better at destroying them.
The first immunotherapy drug to consistently improve survival, Yervoy (from Bristol-Myers Squibb), was approved in 2010 for treating metastatic melanoma (one that has spread to other parts of the body) and there are now at least ten immunotherapies approved for treating cancer with several approved for many different cancers. The fast pace of research is clear from the 2,000 or so ongoing clinical trials of new immunotherapy drugs. That will drive growth of the global cancer immunotherapy market from $40bn in 2017 to $170bn by 2028.
Miraculous results with some cancers
Immunotherapy can have miraculous results for particular kinds of cancer. One famous case is Philadelphia’s Stefanie Joho. Her colon cancer was raging out of control, with a massive tumour appearing in her abdomen despite surgery and chemotherapy. Her oncologist said there were no more treatment options left. However, Stefanie’s sister Jess discovered a clinical trial at Johns Hopkins University and Stefanie joined it. It was a trial of Keytruda, a drug not then approved for colon cancer, but which had helped treat former president Jimmy Carter’s brain and liver cancer. The results on Stefanie were remarkable: her tumour shrank and then disappeared, leaving her free from all signs of cancer. Further investigation showed that Stefanie had a genetic glitch called MMR deficiency; her cancer had many more mutations than usual and it was therefore more likely her immune system would recognise it and attack it with the assistance of Keytruda. In 2017, America’s Food and Drug Administration (FDA) approved Keytruda to treat colon cancers of Stefanie’s type. There are many similar stories of patients with advanced cancer whose lives have been saved by immunotherapy drugs.
Three key types of immunotherapy
There are three important types of immunotherapy. The first is antibody checkpoint inhibitor therapy (ACIT). ACIT uses monoclonal antibodies (a type of protein produced in a laboratory) to target immune checkpoints, which regulate pathways in the immune system that stimulate or inhibit its action. Checkpoint therapy blocks checkpoints that tumours use to protect themselves from the immune system. This blocking flags up tumour cells so that the immune system can recognise and attack them. The second sort of immunotherapy is known as T-cell therapy, of which CAR-T cell TCR are the best known examples. T-cells are taken from the patient and genetically modified to add a chimeric antigen receptor (CAR), which specifically recognises cancer cells. The resulting modified CAR-T cells are multiplied outside the body and then reintroduced into the patient to attack tumours. CAR-T therapy in the US famously treated the leukaemia contracted by Zac Oliver, a young man from Shropshire, after a Daily Mail fund-raising campaign. He was declared cancer-free last month.
Mixing and matching
One of the frustrations of many early immuno-oncology drugs is that they work very well on only some patients and with only some types of cancer. This is why a lot of effort is now being put into the third approach: combination therapies (CT). They aim to enhance the immuno-stimulatory response by combining two different antibody therapies, or an antibody therapy with a conventional pharmaceutical one. Bristol-Myers Squibb’s mix of Opdivo and Yervoy, for instance, combines two ACIT antibody therapies, each targeting one of the body’s two main proteins critical to the immune system’s ability to control cancer growth. The Opdivo+Yervoy combination is the first treatment for metastatic melanoma with a better-than-50/50 chance of patients responding. Another example is the combination of Keytruda with chemotherapy for lung cancer, which is more effective than either alone.
New lines of enquiry
Two further categories of immunotherapy exist, but here drugs are only just beginning to emerge. Oncolytic virus therapies (OVT) are being pioneered by Amgen. A virus is injected into the tumour, enters the cancer cells (but not healthy ones) and makes copies of itself so the cancer cells burst and die. Amgen’s Imlygic uses modified herpes viruses to do this. Cancer vaccines, meanwhile, expose the immune system to an antigen that the immune system then recognises and destroys – in this case, cancer cells.
With more and more immuno-oncology drugs and other treatments for cancer being approved, doctors need to find out which drug is most suitable for a particular cancer in any specific patient. This is particularly important for certain cancers, such as Stephanie Joho’s, where immunotherapy can produce a miraculous cure. The answer lies in genomic testing, an area covering people’s genetic predispositions to certain types of cancer as well as the genetic make-up of tumours, which can help discern how they might develop.
There are now several genetic tests for tumours on the market that can indicate the most effective treatment. This helps to make targeted precision cancer treatment a reality. Examples of such tests are Oncofocus from Oncologica and FoundationOne from Roche. Given the range of cancers treatable with the checkpoint inhibitors Opdivo, Keytruda and Opdivo+Yervoy, a test called the Tumour Inflammation Signature (TIS) has been developed to help predict whether patients will respond to these drugs.
Since the first effective cancer immunotherapy was approved in 2010, many other single and combination immunotherapies from major biopharma companies have been approved for various types of cancer. Their 2018 sales vary from less than $100m to $7bn.
Opdivo: another miracle cure
The only two super-blockbusters – boasting sales of over $5bn – are Opdivo and Keytruda, which both have sales of around $7bn and have at least nine approvals each for different types of cancer. Stefanie Joho’s colon cancer was cured with Keytruda, and Opdivo has had similarly miraculous effects. The US Cancer Research Institute cites Maureen O’Grady, 62, who in 2009 was diagnosed with stage-four (the final stage) lung cancer that had spread to her liver and heart. She was given a year to live by her doctors. She tried chemotherapy, which had horrendous side effects and merely slowed the growth of the cancer, and also Tarceva, a conventional lung-cancer drug.
She stopped both chemotherapy and Tarceva after discovering a clinical trial of Opdivo at Yale. She joined the trial in early 2010 and found she had almost no side effects from Opdivo. Her first scan after eight weeks on Opdivo showed she was responding dramatically to treatment. The tumours shrank to almost nothing after two years and Maureen was alive and well six years after original diagnosis. Dr Herbst, chief of medical oncology at Yale, said: “In 25 years I’ve never seen anything like it.” The FDA approved Opdivo for lung cancer in 2015. The potential of these drugs, then, is enormous – and small biotechs as well as giant pharmaceuticals are getting in on the act. Below, we look at how investors can profit.
The stocks and funds to consider now
There are four main ways for investors to participate in the success of immunotherapies. The first is to back large biopharma companies that make a substantial proportion of sales from immunotherapies and have promising new ones in the pipeline. Two of these companies – Bristol-Myers Squibb (NYSE: BMY) and Merck (NYSE: MRK) – stand out, with super-blockbusters Opdivo and Keytruda. No other firms at present have even a blockbuster (sales more than $1bn a year) to their name.
The FDA approval history of Opdivo shows how its range of application has expanded following first approval for advanced melanoma in 2014. Approvals for lung cancer and kidney cancer followed in 2015, hepatocellular cancer in 2017 and expanded kidney and colorectal cancer indications in 2018. Opdivo/Yervoy combinations have been approved for melanoma (2015 and 2016) and for kidney and colorectal cancer in 2018. Keytruda has a comparable approval history to Opdivo.
Bristol-Myers Squibb had immunotherapy sales of more than $8bn in 2018, or 35.5% of total 2018 sales, making cancer immunotherapy a substantial proportion of revenue. It is taking over Celgene, a blood-cancer specialist, which in turn has bought Juno Therapeutics, a firm with a pipeline of CAR-T therapies. The combined companies would have had 2018 revenues of $37.9bn.
For Merck, Keytruda’s $7.2bn of 2018 sales made up 17% of total revenue (of $42.3bn). A small immunotherapy portfolio should therefore contain Bristol-Myers Squibb and Merck.
Many smaller firms have pipeline immunotherapies, but no approved drugs on the market; only a few, such as Tocagen (Nasdaq: TOCA) have Phase-III trials (the final stage of clinical tests) in progress. Most are based in the US, which has 30 of the top 46 immunotherapy start-ups; four are from the UK. Investment success depends on the smaller company either being acquired or partnering its key drug with a large biopharma. Brave investors willing to do a great deal of research may wish to explore this sub-sector.
Another approach to the immunotherapy boom is to invest in the industry’s suppliers: companies making things needed to diagnose or develop immunotherapies. Enter Illumina (Nasdaq: ILMN), a world leader in genomic testing used for deciding which drug is likely to be most effective for any particular combination of tumour and patient.
Grail, a company spun out of Illumina and soon to be floated, is developing a DNA-based blood test for the very early detection of cancer. Consider also MorphoSys (Frankfurt: MOR), a supplier of antibodies, many of which are used for cancer drugs.
A fourth way to gain exposure is through funds, although the main biotech and healthcare-orientated trusts do not have especially large proportions of their top-ten portfolio holdings in cancer immunotherapy companies. The Biotech Growth Trust (LSE: BIOG) has Celgene, Illumina, Gilead Sciences and Amgen accounting for 26.1% of its portfolio, while the BB Healthcare trust (LSE: BBH) contains Illumina, Celgene and Bristol-Myers Squibb, jointly contributing 32.6% of the overall portfolio’s value.
Given that most cancer immunotherapy companies are in the US, another option is to track the Nasdaq Biotech index directly. This can be done with the iShares Nasdaq US Biotech ETF (LSE: BTEC), which charges 0.35%. Illumina and immunotherapy groups Gilead Sciences, Amgen, Incyte and Celgene jointly comprise 30% of the index.
The WINTHER trial***, NCT01856296, led by investigators from Vall d’Hebron Institute of Oncology – VHIO (Spain), Chaim Sheba Medical Center (Israel) (Raanan Berger), Gustave Roussy (France) (Jean-Charles Soria), Centre Léon Bérard (France) (Pierre Saintigny), Segal Cancer Centre, McGill University (Canada) (Wilson H. Miller), UT MD Anderson Cancer Center (USA) (Jordi Rodon and Apostolia-Maria Tsimberidou) and University of California San Diego, Moores Cancer Center (USA) (Razelle Kurzrock), aimed to expand precision oncology to patients with advanced solid tumors that progressed after treatment with standard therapies.
For the first time in the clinic, the WINTHER trial applied transcriptomics (RNA expression testing) to tailor precision medicine in oncology to a greater number of patients based on the increased expression of RNA in tumors compared to normal tissues.
303 patients were enrolled in WINTHER; 107 of whom were ultimately treated according to recommendations made by a committee of cancer experts spanning five countries. These patients had been heavily pretreated, with one quarter having received five or more prior lines of therapy. Of the 107 patients treated, 69 received treatment based on DNA mutation profiling, and 38 based on RNA profiling. Overall, the WINTHER trial succeeded in matching personalized therapy to 35% of patients with advanced cancer.
“The strategy employed in WINTHER resulted in a higher proportion of patients treated than in many precision medicine trials. Previous studies have identified potential treatments for between 5% and 25 % of patients based on DNA profiling alone, our findings represent an important step toward delivering on the true promise of precision medicine in oncology,” said Richard L. Schilsky, Chairman WIN Consortium and Chief Medical Officer of ASCO.
In this trial, patients were first evaluated for targetable alterations in cancer driver genes. Those who were not matched to drugs based on DNA alterations received a treatment tailored to the differences in gene expression between patients’ tumors and normal tissues which were assessed using a patented algorithm developed by the WIN Consortium. Comparisons with normal tissues proved essential due to highly variable RNA expression between patients and across normal tissue types. The WINTHER researchers showed that RNA expression can be used to expand personalized therapy options for patients and that normal tissue biopsy is safe and accepted by patients.
Patients who received therapy optimally tailored to their respective DNA alterations, or consistent with the algorithm recommendation for RNA guided treatment, responded better. Patients with a good performance status and a high degree of matching had a significantly longer median overall survival of 25.8 months versus 4.5 months for others. There was also a correlation between degree of matching and progression-free survival independent of the number of prior therapies. “Importantly, our results show that patients treated with a drug or regimen more closely matched to the molecular profile of their tumor, do better,” observed Razelle Kurzrock, co-leader of the WINTHER trial and Director of UCSD Moores Center for Personalized Cancer Therapy.
“Assessing RNA is an important adjunct to DNA profiling for determining precision treatments. WINTHER rings in a new era for personalized medicine in oncology,” concluded Josep Tabernero, Vice-Chairman WIN Consortium, Director VHIO and President ESMO.
A new single-center report has found that the results of next-generation sequencing (NGS)–based molecular profiling for non–GI stromal tumor (non-GIST) sarcomas provided information used to effectively guide clinical management.
A team of authors led by Spandana Boddu, a research assistant at Moffitt Cancer Center in Tampa, Florida, analyzed data from 114 patients with a diagnosis of non-GIST sarcoma who underwent molecular profiling during treatment at the center between May 2013 and March 2017.
“We found that clinical management was affected by NGS results in a small but notable percentage of patients, including those with a diagnosis change (4.4%) and/or in whom therapeutic selection was altered by the treating physician because of findings
(13.2%),” the authors wrote in JCO Precision Oncology. “The genes most commonly affected by pathogenic mutations in our cohort mirror those most widely reported in sarcomas to date.”
Boddu et al used Moffitt’s Personalized Medicine Clinical Service (PMCS) database to identify all non-GIST sarcoma patients who underwent commercial genomic testing between May 2013 and March 2017. A PMCS review of all patients with solid or hematologic malignancies who undergo commercial genomic sequencing is standard at Moffitt.
Each patient’s genomic findings were also included in the Clinical Genomic Action Committee (Moffitt Molecular Tumor Board) database. The database included demographic, clinical, and histologic information, such as the type of genomic test and the source of biopsy specimen. Each gene, mutation, and allele frequency or copy number along with microsatellite status and mutation burden, if available, was also recorded in the molecular tumor board database.
Each patient underwent molecular profiling on the same comprehensive genomic panel on a commercial platform. The authors performed a chart review to retrospectively collect treatments and outcomes data and confirm pathology findings.
The authors identified “clinically actionable” genetic alterations on the basis of the assessment of the commercial testing company and the PMCS review. They also defined genetic alterations as clinically actionable if they had been previously documented as “providing diagnostic or prognostic information or to predict response or resistance to commercially available or investigational agents.”
Boddu et al defined actionability as “predicting response to approved drugs available for the patient’s diagnosis (on-label), for another diagnosis (off-label), or investigational drugs being studied in humans for whom the genetic alteration has been shown to serve as a suggested biomarker for response,” they wrote. “Assessment of clinical actionability was limited to mutations previously reported or likely to be driver mutations based on available literature and functional classification and did not consider analysis of variants of unknown significance.”
Of the 114 patients, slightly over half were female (n = 63, 55%). Patients’ median age at diagnosis was 55 (interquartile range [IQR], 38 to 65) years. Most patients had metastatic disease (85.1%) and had received prior systemic therapy (81.6%). A large majority of patients had soft tissue tumors (n = 94, 82.5%), while the remaining 20 patients had bone sarcomas (17.5%).
Patients’ histologies were consistent with the most common sarcoma subtypes, including leiomyosarcoma (16.7%), well-differentiated/dedifferentiated liposarcoma (12.2%), and undifferentiated pleomorphic sarcoma (10.5%). Chondrosarcoma (7.0%) and osteosarcoma (6.1%) were the most common types of bone tumors.
NGS detected 438 genetic variants among the collection of 114 tumors that were presumed to be oncogenic. Almost all tumors had at least one driver variant (96.7%), while the median number of driver variants per tumor was 3 (range, 0 to 19). Regardless of sarcoma subtype, the most common alterations were in TP53 (36.8%), CDKN2A/B (20.2%), CDK4/MDM2 (19.3%), ATRX (13.2%), and RB1 (13.2%). About 60% of alterations were structural, including 157 amplifications and 66 copy-number losses.
No patients displayed evidence of microsatellite instability. NGS was able to assess tumor mutational burden in 106 patients. The clear majority of these patients had <6 mutations (84.9%). Around 13% of patients were characterized as having intermediate tumor mutational burden (6 to 20 mutations), while less than 2% of patients had >20 mutations.
In 5 cases (4.4%) treating physicians viewed the genomic findings as either diagnosis-changing or diagnosis-modifying. Boddu et al described a “low grade spindle cell sarcoma” being reclassified as a desmoid tumor after the detection of a CTNNB1 mutation prompted additional pathologic review.
Additionally, the diagnosis of “poorly differentiated sarcoma, favor neurogenic tumor/MPNST [malignant peripheral nerve sheath tumor]” was revised to synovial sarcoma after NGS detected a typical SS18-SSX2 fusion. This mutation was then confirmed by conventional testing. “In the remaining three cases, novel or seminovel fusions that were felt to be disease-defining were detected in cases of ‘small round cell sarcoma, not otherwise specified’, including one each of EWSR1-PATZ1, BCOR-ZC3H7B, and PHF1-TFE3,” wrote Boddu et al.
NGS testing reports included a therapeutic treatment recommendation for 88 patients (77.2%). Following Moffitt review of the genomic findings, 56 patients (49.1%) were classified as having an actionable result. Most of these patients had options to pursue both off-label targeted therapy and molecularly matched clinical trial options. Nine of these patients found that their only significant alteration was already known or assumed. These findings included MDM2/CDK4 amplification in dedifferentiated liposarcoma or NF1 in malignant peripheral nerve sheath tumor.
NGS findings guided treatment management in 15 cases (13.2%). This includes patients for whom a standard treatment was preferred over an alternative treatment and patients for whom chosen therapies changed due to a change in diagnosis based on NGS findings. Boddu et al reported that 4 of 15 (26.7%) NGS-influenced treatment plans resulted in clinical benefit such as partial response or stable disease > 6 months.
Boddu et al concluded that clinical genomic profiling altered the disease course of “a sizeable minority” of sarcoma patients at Moffitt. “Looking forward, we expect the number of patients who have actionable NGS findings to steadily increase as more molecularly targeted therapies become available and as genomics becomes increasingly used as a biomarker for immunotherapy response,” they wrote. “At present, our experience is that patients with sarcoma who are most likely to benefit or at least have their clinical course altered by NGS are those with an unclear diagnosis or rarer sarcoma subtypes in which potential genomic targets are not well known, and patients in whom early-phase trials are being considered.”
At least half of patients with cholangiocarcinoma have mutations in their tumors that may be treatable with targeted drugs or immunotherapies that are either experimental or approved for other cancer types. These are available through clinical trials.
Yet when surveyed, half of patients with this diagnosis said their tumor tissue hadn’t undergone molecular profiling to determine if those mutations were present. Why not? Most said they hadn’t known about this kind of testing.
The Cholangiocarcinoma Foundation (cholangiocarcinoma.org) — which supports and advocates for those with this rare cancer that affects the bile ducts — is determined to make sure everyone with the disease learns about and has access to genetic profiling and clinical trial participation. The foundation is working toward that goal through its new program called Mutations Matter, funded with a $125,000 grant from Bayer Pharmaceuticals.
Through a new website (mutationsmatter.org), educational videos and targeted email campaigns, the foundation plans to tell both patients and doctors why this testing should be done as soon as possible after a cholangiocarcinoma diagnosis.
“Profiling needs to be done immediately, so you can plan what you want to do next if it progresses,” Stacie Lindsey, president of the foundation, said in a presentation at the organization’s annual conference, held Jan. 30 in Salt Lake City, Utah. “Cholangiocarcinoma is the most highly targetable among gastrointestinal cancers,” she added — it expresses the most mutations that are potentially treatable with drugs already approved to treat other types of cancer.
The gap in knowledge on this topic lies mainly in the fact that 85 percent of patients with cholangiocarcinoma are treated outside major academic cancer centers, where both tumor profiling and access to clinical trials are standard, Lindsey said. In community treatment settings, she said, oncologists who treat cholangiocarcinoma tend to be generalists rather than gastrointestinal specialists, tumor profiling may be limited or discouraged, and access to clinical trials may be restricted or not offered.
When it comes to a rare cancer like cholangiocarcinoma, the fact that just 5 percent of adults with cancer participate in clinical trials is “tricky,” she said, because insufficient enrollment can lead to studies being canceled or pharmaceutical companies and academia failing to invest in them.
The foundation conducted its survey of 132 patients and their profiling histories a year and a half ago, when the immunotherapy Keytruda (pembrolizumab) was approved for all solid tumors that are considered microsatellite instability-high, meaning that they have trouble repairing their own DNA when it’s damaged. About 3 percent of patients with cholangiocarcinoma have that status and are eligible for the treatment, but they can’t know that unless their tumor tissue is profiled, Lindsey said.
Of the half of respondents who said that their tumors had been profiled, 62 percent noted that the test results had influenced their treatment decisions.
Lindsey cited 51-year-old survivor Matt Reidy as an example. He had his tumor profiled, and when Keytruda was approved two years later, it turned out he was eligible to take the drug.
“I started Keytruda, and within four months I had a complete response,” Reidy is quoted as saying on the Mutations Matter website. “I continued the therapy for 18 months total, and three years after starting, I remain cancer-free and consider myself cured.”
Lindsey said the foundation is running Mutations Matter with help from a variety of partners.
Komodo Health gathers data on where patients are being treated and how, to pinpoint where education is most needed. If hot spots are found at sites within the country, the foundation can wage email campaigns targeted to community oncologists there. Digital communications company DMD is in charge of those targeted email efforts, and public relations experts at EIN Communications created a communications plan and are reaching out to media.
It was D2 Creative that made the simple, digestible videos — called “illuminations” — that are available in six languages and aimed at patients and doctors. The Cholangiocarcinoma Foundation has established a blueprint for outreach to other nonprofit organizations that might benefit from sharing the videos with their members, Lindsey said.
Finally, Perthera Inc., a health care artificial intelligence company, is acting as a concierge for patients, facilitating genetic profiling for each and then generating a free report, including a list of potentially relevant clinical trials and how to contact them. Perthera is offering its services at no cost during the program’s first year, which began in June 2018.