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
For international travellers, taking their PCR test swab is only the beginning of the Coronavirus PCR test journey.
In a meeting with Robert Courts MP, Minister for Aviation, Maritime & Security, Oncologica explained the genetic science and logistics applied daily to thousands of PCR test swabs to determine positive or negative results.
Furthermore, the genomic sequencing of travellers’ positive PCR test results is vital for identifying high-risk COVID-19 variants of concern, to alert NHS Test and Trace and help prevent high-risk virus variants from entering the UK population across our borders.
To help guide the Minister through the PCR swab test journey, Oncologica presented a video specially created to outline the keys stages of genomic testing and the impact this data driven approach is having on identifying and curbing high-risk variant transmission via incoming international travellers.
Step 1: The Coronafocus Covid-19 PCR Test Self-Swab Kit
A lot of work happens before PCR swab tests arrive for processing at Oncologica’s specialist genomic testing laboratory. Travellers across the world first order PCR test kits online at covid-19.oncologica.com. A useful FAQ guide helps link travellers to government travel testing rules and details when kits are dispatched to coincide with PCR test date requirements. Coronafocus self-swab PCR test kits can be used for Pretravel-Fit to Fly, Day 2 Green list country and Day 2 Day 8 Amber list country arrivals and for Day 5 Amber list Test to Release certificates.
The COVID19 PCR test kits are dispatched by courier to customers and each kit includes a packaged self-sample swab, liquid tube with a unique barcode, sealable bag, swab instructions and a prepaid Royal Mail tracked return envelope(s). Travellers receive instructions electronically when placing their orders, explaining how to register and activate their PCR travel test kit by inputting the date and the time the swab was taken into the online customer dashboard prior to return of their kits to the lab for analysis.
Step 2: Sample return
Travellers can drop the PCR tests in the tracked return envelopes into Royal Mail priority post boxes located in every town or village , return the PCR sample(s) by hand to the 24/7 Oncologica lab or contract their own private courier.
Step 3: The lab testing process
When a swab is returned to Oncologica, scientists prepare the samples for COVID-19 PCR testing. They log the swab into the system with the unique sample number which tracks the PCR swab sample through the process and ensures that names are not directly on display.
The scientists prepare the samples for the Polymerase Chain Reaction (PCR). This checks whether the virus’s genetic information is present in the sample. The swab gets placed in a chemical solution that breaks apart and releases nucleic acids — the RNA whose unique sequences help identify the presence of the virus in a sample.
Coronavirus is a single-stranded RNA virus and needs to be converted into DNA using specific enzymes to enable the PCR process.
The PCR testing technique copies the genetic information and flags any matches with viral sequences.
We are all familiar with the DNA double helix. Each strand is made up of building blocks called nucleotides. PCR breaks these apart, into single strands in the solution. Then, strands of DNA that are custom-built to match the virus’s unique genetic sequences are introduced. If there is viral DNA in the sample, these primer strands will naturally latch onto the complementary strands. In this way, each strand of matching viral DNA gets doubled. The series of events keeps repeating to increase the amount of viral DNA, so that even tiny amounts of virus in the swab sample create copies.
When DNA primers bind with viral strands in the sample, they activate fluorescent signals that help track these genetic matches. In duplicating the viral DNA, every new strand of DNA creates a little light. The PCR doubles the strands in every cycle for exponential growth and light creation. The light cannot be seen by the human eye and is read by the PCR instrument. If a sample includes the virus, then the DNA primer strands bind, and lights accumulate to a level that signifies a positive test.
Oncologica have capacity to process up-to 40,000 PCR test swabs daily. COVID-19 PCR swab test results are very specific and sensitive and are accessed via the online customer dashboard usually within 24 hours from booking the swab sample into the laboratory. This is to ensure individuals follow government guidelines to protect their health and prevent virus transmission to families and the wider public.
Step 5: Sequencing Positive Results
The UK’s Test and Sequence strategy requires any positive PCR test samples to be sequenced in government-accredited labs. Oncologica is a leader in COVID-19 PCR testing and sequencing.
Our highly trained scientific and medical team use state of the art high-volume PCR and sequencing instrumentation to support the demands of the international travel testing programme.
The Integrated PCR testing and genomic sequencing strategy is pivotal in identifying emerging high-risk variants on a global scale. These variants can cross our borders rapidly, so sequencing them effectively detects and alerts NHS Test and Trace to emerging strains to help prevent them becoming prevalent in the population. Sequencing is also important in monitoring vaccine efficacy, informing new vaccines designs and for protection from future escalating outbreaks.
Oncologica PCR test options are detailed here
Genomic sequencing is yielding critical insights into how the SARS-CoV-2 virus mutates, which variants are the most infectious and how it travels from place to place. Yet sequencing is still rare in most countries, and more than a year since the virus made its deadly debut much about it remains a mystery.
Great Britain has emerged as an international leader in deciphering the coronavirus’s genetic code: as of the end of December, British scientists had sequenced 7.4% of the country’s COVID-19 positive samples vs. the U.S.’s 0.3%.
A new government regulation is accelerating the pace of genomic research into the virus and cementing the U.K.’s leadership position in the field. As of February 15, all international travellers to Great Britain from “red list” countries are required to quarantine for 10 days and undergo a polymerase chain reaction (PCR) test, the gold standard for coronavirus detection, on days 2 and day 8. If the traveller tests positive, the sample must be sent to a government-approved lab for genomic sequencing. The rule was prompted by fears regarding coronavirus variants that might prove resistant to vaccines. The B.1.1.7 (Kent) variant, which was first identified in the U.K., does not appear to be vaccine resistant.
To find out more about the U.K.’s sequencing work, ThermoFisher spoke with Dr. Marco Loddo, PhD, and Prof. Gareth Williams, MBChB, PhD, co-founders of Oncologica, the first government-approved provider of COVID-19 PCR testing and genomic sequencing laboratory services.
The pair discussed the company’s COVID-19 testing and SARS-CoV-2 sequencing work to control the spread of the coronavirus.
Q: Oncologica, is a precision oncology services laboratory, focusing on molecular profiling of cancer patients to enable targeted therapies. How did you get into the COVID-19 testing space?
Dr. Loddo: It has been an interesting transition for us. We founded our company in 2014 with a focus on genomic sequencing to identify patients more likely to respond to certain targeted cancer therapies. When the pandemic began, our initial involvement with COVID testing was to offer it to vulnerable, immunocompromised cancer patients. Subsequently, we were invited by the British government to take part in its national testing program. Our testing has expanded over the past year, and now we’re testing for private companies, educational institutions and others. More recently, we’ve become one of the companies testing international travellers.
The government’s test-and-sequence program is probably the strongest strategy for protecting the borders from new variants of concern.
Q: Has the TaqPath test been your main tool for COVID testing?
Dr. Loddo: We have been using the TaqPath COVID-19 CE-IVD RT-PCR Kit exclusively. TaqPath’s huge advantage is that it’s a multiplex assay — which means that it targets multiple areas of the SARS-CoV-2 genome, enabling it to detect the presence of the virus even when it’s a mutated version. We’ve found that other company’s tests can struggle, particularly if they’re single- or double-target assays, to pick up some of the new variants. With the TaqPath kit, we’re able to identify all the variants. In fact, part of the new government regulations is that single target RT-PCR tests are no longer allowed for international arrivals; labs must now use a multiplex test that targets at least two genes.
Q: For sequencing under the new travel regulations,* you have been validating the Ion AmpliSeq SARS-CoV-2 Research Panel. Why did you choose it for this work?
Dr. Loddo: In genomic sequencing, there are two parameters, “coverage” and “depth,” which determine the accuracy of the sequencing. The coverage we can achieve with AmpliSeq, compared to other sequencing technologies, gives us more accurate data that we can use to more precisely identify new variants, which was very important to us. On a side note, the minimum coverage requirements set by the government are quite low—50%—while Ampliseq covers more than 99% of the SARS-CoV-2 genome, including all serotypes. It’s really important to quickly link information about new variants to the test and trace program.
Q: Do you anticipate you’ll be testing a lot of samples through the international arrivals program?
Dr. Loddo: Our capacity is 40,000 tests per day. We had consistent volume of between 15,000-17,000 tests per day until lockdown caused a drop in testing. With new requirements, we expect an extremely high volume of samples from international arrivals, so we are ready to fill up our capacity for this program. Scaling testing will involve infrastructure expansion and automation, which will enable us to process 40,000 tests per day.
Q: What is the current state of knowledge about the coronavirus variants in the U.K.?
Dr. Loddo: As you know, we had the emergence of the B.1.1.7 (Kent) variant which spread very rapidly. It’s now the most prevalent strain in our country. We even picked up the new B.1.1.7 (Kent) cluster with the E484K mutation, a mutation in the spike protein. This is a variant of concern because, particularly when coupled with the 501Y mutation, it is associated with antigenic change and vaccine bypass.
When the B.1.1.7 (Kent) variant was first characterized in 2020, it had around 26 mutations. Now we’re picking up between 31 and 36 mutations, so the virus is continually changing. It’s so important to pick up these small mutations, which can make a big difference in terms of antigenic change. These changes in the antigens, the virus’s surface proteins, are concerning because a vaccine may no longer recognize the antigens once they’ve changed, and it’s that recognition of the antigens that triggers the immune response to fight off the virus.
Testing and sequencing must be a global endeavour. That’s the only way we can protect our communities from variants traveling around the world.
Q: Once large numbers of people are vaccinated against the coronavirus, is there still a role for genomic sequencing?
Prof. Williams: As more people are immunized, the selective pressure driving these emerging variants will increase. Natural selection will determine which strains become prevalent in the population, as mutations that increase the virus’s transmissibility or ability to evade immune response are most likely to persist. That’s why sequencing is needed to track these strains as they emerge. And again, it’s really important to have full sequencing coverage because the mutational clusters are distributed along the whole of the coding sequence.
Q: What does the future hold for testing and genomic sequencing as a pandemic containment strategy?
Dr. Loddo: This pandemic has really put testing and sequencing on the map, highlighting the importance of both. We have learned how the variants can come across borders very rapidly, often undetected with asymptomatic individuals. I think testing and sequencing are definitely going to be a part of protecting ourselves from future pandemics— being able to identify not just the pathogen and its variants but also the individuals most at risk using immune analysis.
A Look Ahead
Over the coming year, NGS will play a critical role in enabling immune repertoire profiling to determine vaccine response, assess vaccine efficacy and guide the development of more effective, targeted vaccines. Already, clinical researchers are using NGS to better understand immune response to vaccines and efforts are underway to create a repository for COVID-19 patients’ immune repertoires to advance global research and vaccine discovery efforts.
The U.K.’s genomic sequencing requirement began March 1, see interview on ThermoFisher Behind the Bench
The TaqPath COVID-19 CE-IVD RT-PCR kit is labeled “For In vitro Diagnostic Use”.
The Ion AmpliSeq SARS-CoV-2 Research Panel is labeled “For Research Use Only. Not for use in diagnostic procedures.”
Oncologica, the world-leading cancer medicine and Covid-19 genomic sequencing laboratory was the first UK laboratory to receive approval by UKAS and the Department of Health and Social Care (DHSC) to perform Covid PCR testing requirements for the for day 2 and day 8 as part of the new requirements for Covid International travel certification.
Our high throughput laboratory can process up-to 40,000 Covid-19 tests per day, and underwent a rigorous audit by the DHSC and UKAS inspectors of our Oncology and Covid-19 PCR genomic testing processes for personalized cancer medicine and Covid-19 PCR testing /viral genomic sequencing.
These testing capabilities are expediting the UK’s return to work and mitigating the risk of superspreading Covid-19 variants in the population. Our state-of-the-art precision cancer medicine genomic profiling services provide cancer patients with new therapeutic opportunities should standard treatment protocols such as chemotherapy prove inadequate.
Assessments were made of our laboratory’s patient sample collection process, interpretation of results methodologies, turnaround times, as well as an inspection of how we educate and train medical laboratory scientists and clinicians, and how we communicates and consults with health care professionals.
From February 15th, 2021, all international travellers to the UK from “red list” countries have been required to quarantine for 10 days and undergo a polymerase chain reaction (PCR) Covid-19 test, this is the gold standard for coronavirus detection. On days 2 and 8, if the traveller tests positive, then the sample must be sent to a government-approved lab for genomic sequencing. This is to alert health professionals to potential superspreading coronavirus variants e.g., the UK Kent, Brazilian and South African variants
“It is an honour to be the first UK laboratory Covid PCR test and release provider to achieve accreditation for our Covid-19 International travel testing service. At Oncologica, we are committed to achieving and maintaining the highest standard of quality and service in all aspects of our laboratory testing,” said Dr Marco Loddo, Co-Founder and Scientific Director at Oncologica.
“This commitment is underpinned by the hard work of our entire quality, bioscience and administration teams which has resulted in our achieving this approval.”
“We are immensely proud of Oncologica achieving government approval as the first UK genomic testing laboratory in the UK placed on the Governments provider list to undertake day 2 and day 8 Covid-19 PCR testing for travel which is no mean feat.” said Professor Gareth Williams, Co-Founder and Medical Director at Oncologica.
“We are committed to providing a first-class genetic testing service to all our clinical partners, patients, business community and the general public, and we demonstrate the highest quality standards whether it is for improving cancer treatment opportunities for patients or for Covid-19 testing across the community. Covid-19 testing is being undertaken for businesses, offices, factories, educational institutions, and transport networks facilitating a safe return to work and enabling people to travel.
On receipt of our Coronofocus© self-sampling PCR kits, we extract the RNA genetic material and copy it into DNA. Now if the virus is there, it is in a DNA form. We put it into a PCR reaction (Polymerase Chain Reaction) and take short snippets of DNA and match these to the virus DNA.
If we find the virus DNA, we start a chemical reaction that copies the virus again and again. We then look at the sample copies. If there is no reaction, then no virus is detected. The Oncologica Covid-19 PCR test is very specific, and sensitive. If the Oncologica test finds it, you can believe it.
“We understand the importance of our medical genomic laboratory to patient care. Therefore, for those who use our Oncofocus© cancer and Coronofocus© Covid PCR tests, this accreditation gives added assurance that our testing is performed to the highest standards for rapid and accurate results,” added Dr Marco Loddo.
The emergence of Covid-19 variants are a potential threat to the successful global vaccination programmes. Like all viruses, SARS-CoV-2 evolves over time through the acquisition of random mutations in its genome which is an innate characteristic of viral replication. Mutations have the potential to increase the virulence of the virus by for example increasing the transmissibility and/or the severity of the disease.
Of more concern is for the variant to evade the protective immunity generated by previous infection or by vaccination. At least three designated “variants of concern” have been reported including B.1.1.7 (Kent) which was first identified in the UK and drove a surge in cases, B.1.351 (South Africa), which was first identified in South Africa, and P.1 (Brazil), which was first identified in travellers from Brazil who were tested at a Japanese airport.
This threat is being mitigated though Covid-19 sequencing for people who test Covid-19 positive following PCR/antigen swab testing.
Rapid sequencing of swab positive cases enables immediate mobilization of NHS Track and Trace services to prevent the spread of high risk variants in the community.
Test and sequence has been introduced for international travellers arriving in the UK. All international arrivals must undertake PCR Covid-19 testing and quarantine for 10 days. The PCR test is required on or before day 2 and on or after day 8 of their quarantine period. For variant surveillance Covid-19 sequencing is required for cases testing positive.
Testing and sequencing needs to be completed in a short time window (72hours) so that the information can be effectively actioned, namely identifying and isolating individuals carrying high risk Covid-19 variants. To achieve this rapid reporting time Oncologica has established Coronofocus (https://covid19.oncologica.com ), an integrated Test and Sequence platform to combine high capacity PCR testing with SARS-CoV-2 variant identification. Notably Oncologica utilises semiconductor sequencing technology that enables >99% coverage of the viral coding sequence enabling the precise identification of Covid-19 variants.
Coronafocus provides an effective solution to rapid test and sequence demands and is helping contribute to the UK surveillance programme which is preventing the spread of variants that can potentially circumvent vaccine immunity.
Glioblastoma is the most aggressive form of brain cancer, with debilitating symptoms including seizures, memory loss, difficulties in language processing, muscle weakness and visual changes. The standard treatment for glioblastoma involves a combination of surgery, radiation and chemotherapy but have limited impact on survival with the five year survival rate being around 7%.
The exponential increase in modern anti-cancer agents called targeted therapies and immunotherapies are directed at the genetic DNA mutations that underlie the development and progression of cancer. Targeted agents therefore offer the great advantage that they directly attack the cancer cells but leave normal cell relatively undisturbed. Targeted agents therefore show increased specificity and reduced toxicity when compared with conventional chemotherapy.
One of the hurdles to the implementation of targeted therapies into routine clinical practice has been lack of comprehensive genetic screening for these therapy linked DNA mutations at diagnosis. The processing of the tissue biopsies using formaldehyde and wax embedding for diagnosis results in fragmentation of the DNA which makes analysis for mutations a challenge.
In our recent study we show that semiconductor sequencing can be used to robustly screen the fragmented DNA and RNA from routine glioblastoma biopsy/resection samples. This enables comprehensive DNA profiling to be undertaken as part of the routine diagnostic workflow allowing linkage of detected mutations to a broad range of potential targeted therapies and immunotherapies that can be considered should standard treatment protocols fail to control the disease.
The Covid-19 pandemic has had major impact on the social and economic activities of the United Kingdom and has resulted in many deaths. The two major initiatives to address the pandemic has been the establishment of high capacity Covid-19 testing coupled to track and trace and the development of vaccines. Oncologica has contributed to the pandemic by establishing an integrated Covid-19 test and sequencing platform that is being used to control the spread of the disease across the community and also assess the impact of the vaccines in relation to the different Covid-19 variants.
During the early stage of the pandemic Oncologica initiated Covid-19 PCR/antigen testing for the protection of vulnerable immunocompromised cancer patients. Since May 2020 Oncologica has contributed to the national testing efforts as part of the volunteer Covid-19 Testing Network to support the DHSC Covid-19 National Testing Programme covering care homes, local authorities, schools and symptomatic testing across test sites.
Oncologica has now extended its testing more broadly to support businesses, offices, factories, educational institutions, healthcare and transport (aviation, shipping and railway networks).
To date we have undertaken over 600,000 Covid-19 tests. Our contribution to the UK national efforts to address the Covid-19 pandemic was recently recognised by our shortlisting, as part of the Covid-19 Testing Network [CTN], for the Special Covid-19 UK Response Project Award https://www.pmi.org.uk/awards2020-special-COVID-19-award
Oncologica has been listed as an approved government provider for general testing and for the test to release scheme https://covid19.oncologica.com/. Following the latest Government requirements for international arrivals Oncologica now provides genomic sequencing of positive cases in compliance with the new guidelines.
To facilitate the release of lockdown, to aid economic recovery and to enable people to travel we have now increased Covid-19 testing capacity to 40,000 tests/day and optimised our testing workflow to provide the rapid reporting of results with a 12 hour turnaround time.
Oncologica presents data relating to the performance of the Oncofocus test and the identification of new treatment options for patients with advanced cancers “The actionable genomic mutational landscape in solid tumours”.
Advances in somatic cancer genetics and genomic profiling has led to the development of targeted drugs and immunotherapies that are directed against the cancer genes that cause malignancy. These new anti-cancer agents, which specifically target cancer cells, are associated with much higher response rates when compared with conventional chemotherapy. Moreover targeted agents and immunotherapies specifically directed at cancer cells leave normal cells undisturbed and therefore have much fewer side effects. In contrast chemotherapy stops normal cell dividing leading to serious side effects such as hair loss, nausea, anaemia and infections.
In routine clinical practice cancer gene testing for targeted treatments is restricted to a small number genes applied to only a few cancer types e.g. EGFR, ALK, ROS, PD-L1 and TRK in lung cancer, HER2 in breast cancer, BRAF in melanoma and RAS and RAF in bowel cancer. However these mutations are linked to only a handful of targeted agents and immunotherapies. Importantly over 750 targeted agents and immunotherapies have now been developed against hundreds of cancer genes and these mutated genes are found across all tumour types such as glioblastoma, pancreatic, prostate, kidney, ovarian, lung and lymphoma. However these treatment options remain undiscovered for many cancer patients because tumours are not routinely tested for these cancer genes.
To address this unmet clinical need Oncologica has developed the Oncofocus test which can be applied to all tumour types enabling all modern targeted anti-cancer agents and immunotherapies specific to a patient’s individual tumour to be identified. Here we present exciting data at the ASCO conference showing that Oncofocus precision oncology testing is able to identify personalised treatment options in >90% of patients with advanced cancer providing potential linkage with over 750 modern anti-cancer agents.
Immunotherapy, in which the body’s own immune system is harnessed to kill cancer cells in patients with advanced disease, is proving a powerful treatment in around 15% of cancer patients. Importantly this type of treatment can be used to treat a broad range of different tumour types including lung, breast and bladder cancers and melanoma.
The patients who are likely to respond to such treatment can be identified by analyzing the tumour biopsy with a special stain called the PD-L1 test. Tests which are able to identify a patient likely to respond to a particular treatment are called companion diagnostic CDx assays. Oncologica, in collaboration with AstraZeneca, has recently completed a study involving the participation of internationally recognised pathologists to assess the performance of one of these tests, called the VENTANA PD-L1 (SP263) Assay in lung cancer.
Preliminary findings were presented at the ESMO 2018 congress in Munich, Germany. The study has now been completed and the findings recently published in the Journal of Thoracic Oncology, a leading journal in the field of lung cancer. We have shown that assessment of tumour cell (TC) scores by expert pathologists is highly reproducible in lung tumour samples using the VENTANA PD-L1 (SP263) Assay, thus building confidence in the performance of this test as a companion diagnostic for anti-PD-L1 immunotherapy.
This will help ensure that patients who may benefit from immunotherapy are correctly identified.
A major trial of an immunotherapy drug has shown it can be effective in some men with advanced prostate cancer.
The men had stopped responding to the main treatment options.
Researchers found that a small proportion of men, described as “super responders”, remained well even after the trial ended, despite a very poor prognosis before treatment.
Last week it was reported the same drug had proved effective in treating advanced head and neck cancers.
What is immunotherapy?
Immunotherapy uses our own immune systems to recognise and attack cancer cells.
It’s already being used as a standard treatment for some cancers such as melanomas – and being tested on many others too.
- Cancer immunotherapy drug ‘prolongs life’
- Prostate cancer drug hailed as ‘big deal’
- Half of people surviving ‘untreatable cancer’
What did the study find?
It found that one in 20 men with advanced prostate cancer responded to the drug pembrolizumab – and saw their tumours actually shrink or disappear altogether.
Although a relatively small number, some of them gained years of extra life, the study in the Journal of Clinical Oncology found.
A further 19% saw some evidence of improvement.
But most patients in the study lived for an average of eight months on the drug.
The phase II clinical trial, led by the Institute of Cancer Research and the Royal Marsden, involved 258 men with advanced prostate cancer who had run out of all other options on treatment.
What happens next?
The most dramatic responses were seen in patients whose tumours had mutations in genes involved in repairing DNA.
Researchers are now investigating whether this group might benefit the most from immunotherapy in a larger trial.
But first, a test to pick out who will respond best is needed, so that doctors know which patients to give it to.
What is prostate cancer?
It’s the most common cancer in men in the UK, with around 47,700 diagnosed in the UK each year.
The number of people diagnosed has been rising over the last 10 years.
This is probably because the population is getting older and more people are having PSA tests.
Around 30% of men with advanced or stage 4 prostate cancer survive their cancer for five years or more after diagnosis.
What do experts say?
“Immunotherapy has had tremendous benefits for some cancer patients, and it’s fantastic news that even in prostate cancer, where we don’t see much immune activity, a proportion of men are responding well to treatment,” says Professor Paul Workman, chief executive of The Institute of Cancer Research.
“A limitation with immunotherapy is that there’s no good test to pick out those who are most likely to respond.
“It’s encouraging to see testing for DNA repair mutations may identify some patients who are more likely to respond, and I’m keen to see how the new, larger trial in this group of patients plays out.”
Professor Johann de Bono, a consultant medical oncologist at The Royal Marsden NHS Foundation Trust, was one of those who led the study.
He said: “We don’t see much activity from the immune system in prostate tumours, so many oncologists thought immunotherapy wouldn’t work for this cancer type.
“But our study shows that a small proportion of men with end-stage cancer do respond, and crucially that some of these men do very well indeed.
“We found that men with mutations in DNA repair genes respond especially well to immunotherapy, including two of my own patients who have now been on the drug for more than two years.”
Last week, a separate trial found the same drug kept some people’s advanced head and neck cancers at bay for an average of two years – five times longer than under chemotherapy.
Both studies are part of a growing body of research suggesting immunotherapy could offer hope to an increasing number of cancer patients.
An immunotherapy drug that could save some cancer patients from the ordeal of extreme chemotherapy may also help them live longer, researchers say.
In a trial, pembrolizumab kept head and neck cancers at bay for an average of two years – five times longer than under chemotherapy.
The patients also suffered far fewer side-effects.
Cases of head and neck cancers are rising in the UK and most are diagnosed late, when they are harder to treat.
‘I can get on with my life’
Derek Kitcherside, 70, from Leicestershire, believes he wouldn’t be here without pembrolizumab.
He was diagnosed with cancer of the voicebox in 2011. When he started coughing up blood three years later, after receiving standard treatment, he was told the cancer had spread to his lungs and was probably incurable.
Derek asked to go on a drug trial and travelled to London every three weeks for two years for treatment with pembrolizumab.
“My tumour was shrinking all the time and I felt a bit better every time I went,” he said. “It made a huge difference to my life.”
Regular scans show the disease is now stable and the tumour is still getting smaller.
“I’m very pleased I can get on with my life,” Derek said.
“I don’t think I’d be here without it.”
What is immunotherapy?
It is a treatment that does not kill cancer cells itself but instead stimulates the body’s immune system to attack them.
Pembrolizumab is already being used to treat a wide range of advanced cancers, including melanoma – a type of skin cancer that spreads easily.
Experts believe the drug has the potential to treat many more.
When is it used?
Normally, immunotherapy is used after standard treatments like chemotherapy have failed but this trial, in 882 patients from 37 countries, suggests it should be used earlier – and for some people it should be the go-to option.
The drug is given to patients regularly through a drip when their cancer has returned or spread, and is considered incurable.
Why is it better than current treatment?
It is kinder, safer and can keep patients alive for longer, the study in The Lancet found.
But it may not work for everyone.
In people with advanced head and neck cancer who responded to the drug – one in four – their cancer shrank or stabilised for an average of 23 months.
By comparison, although more patients (36%) responded positively to standard chemotherapy treatment, the improvements lasted on average for only four and a half months.
Those with larger, more aggressive tumours were given the drug in combination with chemotherapy to help slow progress of the disease – which was kept in check for an average of seven months.
So who could benefit?
The trick is identifying people with tumours that will respond, says Prof Kevin Harrington, oncologist at The Royal Marsden NHS Founation Trust and professor of biological cancer therapies at the Institute of Cancer Research, who led the study,
A test for the presence of immune marker PD-L1 in the tumour means doctors can work this out.
Prof Harrington says approximately 85% of people with advanced or relapsed head and neck cancer would be eligible for pembrolizumab – around 1,300 patients a year.
Why is it kinder?
At the moment, the recommended treatment is a toxic combination of chemotherapy and antibody therapy, which often makes people feel very sick.
The extreme treatment can also cause damage to the kidneys, hands and feet.
Patients given the immunotherapy drug experienced far fewer side-effects.
“It’s more sensible and less toxic – patients live longer and feel better,” says Prof Harrington.
What does this mean for patients?
“This study is very exciting”, says Prof Paul Workman, from the Institute of Cancer Research.
“Firstly because it shows that immunotherapy can have dramatic benefits for some patients with head and neck cancer when used as a first-line treatment, and secondly because the researchers have devised a test for picking out who is most likely to benefit.”
He said all new drugs coming on to the market should be accompanied by a test to target their uses as precisely as possible.
In the US and the EU, pembrolizumab has been approved for use on its own and with chemotherapy for advanced head and neck cancer, but not yet in the UK.
The National Institute for Heath Care and Excellence is currently appraising pembrolizumab and it could be approved for use on the NHS by next summer.
Facts on head and neck cancer
- Around 12,000 people in the UK are diagnosed with head and neck cancer each year
- Half are diagnosed at stage III or IV when it is hard to treat
- Most cases are linked to smoking and alcohol but the recent rise in cases seems to be linked to HPV (human papillomavirus)
- This virus infects the skin and cells lining the inside of the body and can be spread through close skin-to-skin contact
- Boys and girls are now being vaccinated against HPV at school, but it will be several decades before HPV stops being a risk factor
Mapping the binding sites of antibodies utilized in programmed cell death ligand-1 predictive immunohistochemical assays for use with immuno-oncology therapies
Oncologica has participated in a study, led by AstraZeneca, to further improve the tests that are used to pin point the patients most likely to respond to a new type of anti-cancer treatment called “immune-therapy”. These tests are known as Companion Diagnostic (CDx) tests.
Immune-therapy is now becoming a front-line treatment for many tumour types. Immune Checkpoint Therapy, is an immune-therapy which targets a protein called PD-L1, expressed on the surface of tumour cells, which exploits the bodies’ immune system to attack cancer cells. The NHS use Immune Checkpoint Therapy to treat patients with the most serious form of skin cancer (melanoma) and aggressive tumour types such as lung cancer. The impact of this revolutionary new treatment was recently recognized by the award of the Nobel Prize for Medicine to Prof A Prof Allison (University of Texas) and Prof Honjo (Kyoto University) who discovered this new approach to cancer therapy.
Immune-therapy doesn’t work for everyone, in some patients it appears to work incredibility well, completely destroying tumours even after they have begun to spread around the body, but for other patients the response can be less dramatic.
Several PD-L1 CDx tests have been approved for use, including the VENTANA PD-L1 (SP263) Assay, VENTANA PD-L1 (SP142) Assay, Dako PD-L1 IHC 22C3 pharmDx assay and the Dako PD-L1 IHC 28-8 pharmDx assay. PD-L1 CDx tests are used to pin-point which patients are most likely to respond to anti-PD-L1/PD-1 directed immune-therapies. During the clinical use of these CDx tests a degree of variance between their performances has been observed and it has been hypothesized that such variances may be caused by the different PD-L1 antibodies, used in these tests, recognizing different parts (epitopes) of the PD-L1 protein.
The AstraZeneca/Oncologica study, identified that any variances in performance between CDx tests (inter-assay variability) are more likely attributable to tumour heterogeneity or test/instrument variables than they are to the antibody epitope. This information will help to further the understanding of CDx testing in PD-L1 immune-therapy in the clinical testing community, maximize the benefits of this type of treatment for cancer patients and drive the adoption of CDx testing.
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.