Innovations in Oncology - Q4 2022

Innovations in Oncology

“New research focuses on unlocking new combinations to outsmart cancer.”

Professor Udai Banerji, Deputy Director of Drug Development, The Institute of Cancer Research, London

“Workforce is a global issue, but it’s also something that can be addressed.”

Rachel Cooper, Medical Director Clinical Oncology, Education and Training, Royal College of Radiologists

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New and better treatment combinations to help defeat cancer

Scientists have made progress in discovering new targeted treatments for cancer, helping patients live longer and manage better. New research focuses on unlocking new combinations to outsmart cancer.

Thereis no ‘silver bullet’ to cure cancer. Most cancer patients are treated with combination therapies — treatments that combine two or more drugs or different types of therapy, such as surgery and chemotherapy.

We are entering a new era of combination therapies, using molecules targeting cancer tissue. Combining these targeted agents requires an understanding of the biology of cancer and can lead to more treatment options apart from chemotherapy.

Benefits of combination treatments

By combining treatments — either at the same time or in a certain sequence — researchers can target several different weaknesses within tumours, potentially making treatment more effective and tackling drug resistance.

This can involve treating patients with several drugs that work by different molecular mechanisms or re-sensitising a cancer type to an original treatment by giving the patient another therapy.

Identifying combinations likely to work

Scientists aim to find whether the effects of different combinations of drugs are ‘synergistic.’ This ‘synergy’ occurs when the drugs are working harmoniously to produce an enhanced effect when combined.

In the past, scientists developed new combination therapies by experimenting — relying on trial and error. If one drug worked well in a certain cancer type and another drug was also effective, then they might explore whether they could work better together.

Taking advantage of AI

Over the last decade, the rise of technologies such as artificial intelligence (AI) helped scientists develop smarter and more targeted combination therapies — leading to new

We are entering a new era of combination therapies, using molecules targeting cancer tissue.

potential combinations that humans may not be able to spot. AI tools could save years of development time. At the ICR, we are currently developing a test that uses AI to predict which combinations of drugs are likely to work for lung cancer patients in less than two days. The test analyses largescale protein data from tumour samples and may predict patients’ responses to drugs more accurately than currently possible.

The future of cancer treatment

The next generation of combination therapies is likely to combine new targeted drugs or new immunotherapies with themselves or other types of treatment to improve efficacy. For example, we already know that combining radiotherapy with immunotherapy could make it harder for cancer cells to remain resistant to radiotherapy.

By providing more personalised strategies, combination treatments will play an increasingly important role and could improve many patients’ quality of life in years to come.

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WRITTEN BY

Udai Banerji

Digital: Harvey O’Donnell Paid Media Strategist: Jonni Asfaha Social & Web

Henry Phillips Digital Assistant: Carolina Galbraith Duarte | All images supplied by Gettyimages, unless otherwise specified

“Collaborative and innovative thinking is now needed to expand access to quality cancer care.”

Ann-Lise Mikolajczak Manager, Global Health and Access, IFPMA

“Liquid biopsies that analyse circulating tumour DNA (ctDNA) can give more information on the spatial and temporal heterogeneity of a tumour than traditional tissue genotyping.”

Dr Javier Pascual Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria University Hospitals, IBIMA, Malaga, Spain on behalf of ESMO

Combinations are becoming a cornerstone of cancer treatment

Combination treatments are having an impact in the fight against cancer, but what are they, how do they work and what is to come?

Combination treatments combine two or more treatments for cancer.1 The concept was first introduced in 1965 when combination chemotherapy was used in paediatric patients with acute leukaemia. 2 Since then, we have seen a proliferation of different combinations to treat all forms of cancer.3

Why do we use combinations?

They offer value in:

• Fighting drug resistance – Combining treatments reduces the chances of cancer escaping the effects of treatment or building up its defences over time, therefore improving treatment effectiveness.2

• Improving responses at the first attempt – Everyone’s cancer is different and therefore reacts differently to a treatment. Combining multiple treatments increases their likelihood to respond to it from the get-go.4

• Increasing the magnitude of benefit – Certain medicines, when used together, have the potential to increase the overall treatment benefit (although toxicities sometimes also increase) with the action of one improving the effectiveness of the other and vice versa.1

At the forefront of cancer treatment

We’re only scratching the surface of what’s possible with combination treatments. As advances in research and technology are fuelling our understanding of cancer, we’re able to design new medicines which attack tumours in novel ways and then try them in different combinations to maximise their impact:

• Scientists at The Institute of Cancer Research, London, are researching an artificial intelligence test that can predict which drug combinations are likely to work for a patient in as little as 24 to 48 hours.5

• Immunotherapies recruit the body’s immune system to fight cancer. However, many cancers, termed ‘cold’ tumours, are immunosuppressive and don’t trigger an immune response. Researchers are investigating new combinations of immunotherapies with molecules that can turn them into ‘hot’ tumours to create long-lasting effects.6

Driving innovation to confront cancer

The UK Life Sciences Vision sets out the Government’s ambition for the UK to become the world leader in the discovery, development and launch of new treatments.

To make it a reality in cancer, we must continue to evolve our healthcare system, with combination treatments firmly at the heart of what’s to come.

References

1. Mokhtari, R., et al., 2017. Oncotarget, 8(23), pp.38022-38043.

2. Ayoub, N., 2021.Frontiers in Oncology, 11.

3. Tan, A., et al., 2021. Journal for ImmunoTherapy of Cancer, 9(7), p.e002459.

4. Palmer, A. and Sorger, P., 2017. Cell, 171(7), pp.1678-1691.e13.

5. Icr.ac.uk. 2022. https://bit.ly/3cwfiLX

6. Kokolus, K., 2022. Labroots. https://bit.ly/3PIUZJZ

Job code: MAT-XU-2202950

Date of prep: August 2022

For patients with advanced cancer, for example, validated and adequately sensitive ctDNA assays are useful in identifying actionable mutations to direct targeted therapy.

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Paid for by Sanofi

WRITTEN BY Anju Bhalla

Head of Oncology and Haematology, Sanofi

~Dr Javier Pascual, Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria University Hospitals, IBIMA, Malaga, Spain, on behalf of ESMO

Through public and private sector partnerships, a global initiative innovates for better access to cancer care worldwide.

The global prevalence of cancer is increasing rapidly, presenting an especially heavy burden for people in low and middle-income countries (LMICs). Collaborative and innovative thinking is now needed to expand access to quality cancer care.

In this spirit, the Access to Oncology Medicines (ATOM) Coalition, launched in May 2022 by the Union for International Cancer Control (UICC) and other partners, aims to bring together a wide range of actors around the common goal of improving access to cancer medicines, quality diagnostics and care for people in lower-resource settings.

Increasing availability and affordability

Comprised of approximately 20 global health-focused civil society organisations, medical societies, global oncology centres, as well as 10 biopharmaceutical and generic manufacturers and associations, the coalition can help countries deliver their national cancer control strategies by providing support on capacity building, training and increased availability of essential cancer medicines.

Access to medicine worldwide

The goal is to ultimately improve timely access to essential cancer medicines as well as increase countries’ capacities to provide quality cancer diagnosis, treatments and care. To this end, priority will be given to essential cancer medicines on the World Health Organization’s Model List of Essential Medicines, which outlines the minimum medicine needs for any health system.

The ATOM Coalition partners will work collectively to increase access to generic and patented cancer medicines in 46 LMICs, selected by the coalition based on a number of criteria, including existing health system readiness. In parallel, partners will work together to implement coordinated capacity building, starting with a handful of countries in the first phase of operations.

Solutions-based model

Innovation in oncology should include leading-edge research and development for the next line of treatments that will continue to improve outcomes for patients. Innovation also means developing new access solutions to ensure greater availability of quality cancer diagnostics and care. We are confident that the unique model will spur new types of collaborations, provide tangible solutions to people living with cancer in LMICs and help address the pressing global cancer burden.

How the workforce can unlock government aspirations in cancer treatment

Can the Government produce a 10-Year Cancer Plan with an effective, realistic and properly funded blueprint for the decade ahead?

Government vision

In his foreword to the call for evidence for the 10-Year Cancer Plan, the then-Secretary of State mentions, inter alia, five areas of focus:

• Improvement in early-stage diagnosis

• Boosting the cancer workforce

• Intensifying research

• Better personalised care

• Tackling health inequalities

Current reality

The Royal College of Radiologists’ 2021 Workforce Censuses for clinical radiology and clinical oncology were based on a 100% response rate throughout the UK, and they make sobering reading:

• 17% current workforce shortfall, set to rise to 26% in five years, without significant changes

• Negative effects on waiting lists, patient safety, staff wellbeing and morale

WRITTEN BY Ann-Lise Mikolajczak Manager, Global Health and Access, IFPMA

simply aren’t enough cancer doctors. As our outgoing President Dr Jeanette Dickson put it recently: “Whenever I speak to consultant radiologists and consultant oncologists, the number one issue is workforce.”

The Government understands the importance of good cancer treatment, but too often strategies are created that miss the fundamental problem – there simply aren’t enough cancer doctors.

The RCR has been banging the workforce drum for several years now and we’re beginning to be heard. More training places were granted last year, and we’ve been invited to Select Committees and APPGs to give evidence. But our latest census shows just how much work there is still to do. We need a long-term, fully funded and sustained investment that builds in a permanent increase in training numbers; we need trust funding to employ these trainees; and we need significant investment in IT and equipment – AI and machines, but also an integrated IT system that doesn’t frustrate doctors trying to share vital data. Doctors are, quite simply, burnt out and if we don’t solve these problems, we’re going to see even more cancer specialists leaving the NHS.

• Problem exacerbated by post-Covid backlog

• Increasing cancer prevalence

• Increasing complexity of treatment

• Marked geographical disparity in workforce distribution

It is now estimated that one in two people in the UK will be diagnosed with cancer in their lifetime. The Government quite rightly aspires to earlier cancer diagnosis, but this will exacerbate demand and increase waiting time pressures. Meanwhile, we are seeing more and more patients presenting later, which requires more complex treatment, putting even more pressure on workforce.

The Government understands the importance of good cancer treatment, but too often, strategies are created that miss the fundamental problem – there

Workforce is a global issue, but it’s also something that can be addressed. Any long-term strategy needs to build in a sustained increase in trainee numbers; a clear strategy for global recruitment and a focus on doctor retention.

Solve workforce; then (and only then) can we realistically begin to plan for the future.

Innovative partnership model to improve access to cancer care in LMICs

WRITTEN BY Rachel Cooper Medical Director Clinical Oncology, Education and Training, Royal College of Radiologists (RCR)

The pharmaceutical industry has a pivotal role in cancer care

New approaches could help patients on their cancer journey. These range from adapting therapies for patients’ convenience, changing delivery methods, designing longer-lasting treatments and offering remote support via digital apps to reduce hospital visits.

Senior figure Paul Tredwell believes the pharmaceutical industry has a critical role to play in offering broader support to patients as they live with cancer.

Patient challenges

INTERVIEW WITH Paul Tredwell

Executive Vice President,

WRITTEN BY Mark Nicholls

A key element of that process is gaining a better understanding of the challenges patients face. He points to the example of people unable to get to the hospital during the Covid-19 pandemic and how changes to treatment pathways and drug delivery could help isolated patients going forward.

“That may be a formulation change or making something that was intravenous or injected into a tablet to make it more convenient for the patient to take,” says Tredwell.

Better industry understanding, he continues, is gained from speaking to healthcare professionals (HCPs) and patient groups who can feed back on what is important to them in the treatment journey and where challenges exist with current options.

Chemotherapy delivery

Tredwell is Executive Vice President (EMENA) for Accord Healthcare, which is one of the fastest growing pharmaceutical companies in Europe and one of the largest suppliers of pharmaceuticals to the NHS. They have over 40 oncology-related treatments and are also one of the biggest suppliers of chemotherapy in Europe.

“We supply a third of all the injectable oncology treatments in Europe, so that is a responsibility we take incredibly seriously,” he says. An ongoing challenge in chemotherapy lies in ensuring patients get the right dose and complete their treatment to ensure the best outcome.

“It is about tailoring treatment around a patient’s needs,” he says.

NHS Foundation Trust, a digital health startup focusing on cancer, Care Across, and trusted and reputable cancer charity, Macmillan Cancer Support. It offers support and advice to people to aid their physical and mental wellbeing while undergoing cancer treatment.

The Unify Health app, which is available to patients in the UK, provides accurate and easily accessible information to people on their phones or tablets, in a format they can use. It also links them with local pharmacies if they have specific questions or concerns.

“As such an established provider in oncology, we endeavour to support patients through their journey and we feel that digital is increasingly an important medium to give patients that information,” says Tredwell.

Oncology focus

In the last five years, Accord has increasingly shifted its emphasis toward speciality medicines, including a strong focus on oncology.

Besides its 40 plus oncology-related treatments, it has a further 15 molecules in near-term development, several of which it hopes will become available within the next three to five years.

A new research and development laboratory under construction in London will focus on the “more complex end of the pharmaceutical sector” of biologics and vaccines.

Digital app for patients

Empowering a patient with knowledge and understanding of their condition is important and may improve treatment adherence and outcomes. This can increasingly be delivered with digital tools.

Accord contributed to this with the launch of an oncology patient support app — Unify Health — in July 2021. The app contains specialised content from a world-leading cancer centre, the Royal Marsden

Accord will invest £100 million in the UK over the next two years and is underlining a commitment to UK manufacturing with its sites in Fawdon, Newcastle and Barnstaple, Devon, supplying around 11% of UK drugs. They are also developing several new paediatric oncology products and investing in the manufacturing of plasma-derived products, which can currently be difficult to access globally.

Tredwell says, “We will keep innovating and bringing forward new developments that may help patients at their point of need to support them across their cancer journey. Our ambition at Accord is to ‘make it better.’”

It is about tailoring treatment around a patient’s needs.

Novel insights on clinical applications of circulating tumour DNA for cancer

Liquid biopsies that analyse circulating tumour DNA (ctDNA) can give more information on the spatial and temporal heterogeneity of a tumour than traditional tissue genotyping.

The use of liquid biopsy ctDNA assays in routine clinical practice requires careful attention to pre-analytical processing and the selection of the appropriate technology which may influence the results obtained.

ctDNA use for patients with cancer

The European Society for Medical Oncology (ESMO) Precision Medicine Working Group recently published new recommendations to guide medical oncologists on the clinical applications of this tool at all stages of the cancer care course. It aims to address the main technical aspects of testing and provide some quality standards required for assay reporting.

Liquid biopsies, and ctDNA detected in plasma, are rapidly developing a strong evidence base for use in patients with cancer, as their minimally invasive nature holds the potential of repeated sampling over time.

For patients with advanced cancer, for example, validated and adequately sensitive ctDNA assays are useful in identifying actionable mutations to direct targeted therapy. It may be used in routine clinical practice, especially in situations where tissue biopsies are suboptimal or time is crucial.

WRITTEN BY Dr Javier Pascual Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria University Hospitals, IBIMA, Malaga, Spain, on behalf of ESMO

Answers to scientific questions

ctDNA release is believed to be proportional to tumour growth, with the fastest-growing tumour clones shedding the largest amount of DNA in plasma. Multiple technologies and modalities to detect, extract and quantify it are currently available, making a deep understanding of the analytical and clinical validity and utility of lab-developed or commercial ctDNA assays essential to address scientific and clinical questions.

The ESMO recommendations highlight the main aspects to consider before testing, when reading a report and then translating the findings into action in clinics, including some considerations on potential false negative or non-informative results, limitations for the detection of specific aberrations such as fusion and copy number events and tumour-specific recommendations.

Potential future applications

The new ESMO recommendations also provide insights on other possible applications of ctDNA in the future like identifying early-stage cancers and precancerous conditions in asymptomatic individuals to act in increasing cure rates. The recommendations also review its use for molecular residual disease assessment, molecular relapse monitoring and early assessment of treatment response in which evidence of utility is still lacking.

It may be used in routine clinical practice, especially in situations where tissue biopsies are suboptimal or time is crucial.

Using artificial intelligence to push boundaries for colorectal cancer patients

Surgeons and clinicians are essential in leading advancements in artificial intelligence (AI) for patient benefit. However, more research into the applicability of AI and its safe use is required.

Inrecent years, AI and machine learning (ML) techniques have shown great promise in predicting the diagnosis and prognosis of various diseases and health conditions.

Increase in colorectal cancer

Colorectal cancer is the third most common cancer, with over 1.8 million new cases in 2018; and estimations indicate there will be around 2.4 million cases worldwide in 2035. We owe it to our patients to look at new technologies and how these can provide better knowledge for predicting outcomes and making informed decisions in their cancer care.

AI application in risk assessment

AI has been used in predicting length of stay, readmission and mortality in colorectal cancer patients during research models. In a recent study, data analytics and AI were used to predict patient outcomes after colorectal cancer surgery.

A prospectively maintained colorectal cancer database was used, looking at patients who underwent colorectal cancer surgery between 2003 and 2019. There were 47 patient parameters (demographics, peri/post-operative outcomes, surgical approaches, complications and mortality) reviewed.

Data analytics compared the importance of each variable, and AI prediction models were built for length of stay (LOS), readmission and mortality. Using the system, accuracies of at least 80% have been achieved. The significant predictors of LOS were age, operative time, presence or absence of a stoma, robotic or laparoscopic approach to surgery and complications.

The significant predictors of readmission were age, laparoscopic procedure, stoma performed, preoperative nodal (N) stage, operation time, operation mode, previous surgery type, LOS and the specific procedure. The significant predictors of mortality were age, ASA grade, BMI, the formation of a stoma, preoperative TNM staging, neoadjuvant chemotherapy, curative resection and LOS. The patient’s quality of life during cancer care is paramount, and with AI models, it may be possible to make more informed decisions.

In a recent study, data analytics and AI were used to predict patient outcomes after colorectal cancer surgery.

Potential of AI

AI has the potential to automate detection (eg. image recognition software for pattern recognition using artificial neural networks), improve efficiency (eg. act as a second reader of scans in radiology) and reduce costs. However, models need to have good data with patient safety mechanisms in place and regular quality assurance systems.

All advances must be done ethically, and responsibility for any harm due to ‘technology failure’ or privacy compromise needs to be built with the systems.

WRITTEN BY

Dr Afsana Elanko

Senior Educationalist and Healthcare Leader

WRITTEN BY Professor Jim Khan Consultant Colorectal Surgeon, Clinical Director, Portsmouth Hospitals NHS Trust, Program Chair, Head of Colorectal & Robotic Program, QAH, Portsmouth, Director of Research ASLGBI (Association of Laparoscopic Surgeons of Great Britain and Ireland)

Innovation in oncology should include leading-edge research and development for the next line of treatments that will continue to improve outcomes for patients.

~Ann-Lise Mikolajczak, Manager, Global Health and Access, IFPMA