While healthcare systems are being pushed to capacity, staff and resources are redirected to COVID-19 efforts, and operating theatres are being converted into intensive care units, many people living with cancer may face delays in receiving non-urgent treatment (Gardner, 2020). Those living with cancer also have lowered immunity and will need to take extra precautions during the ongoing pandemic (Cancer Research UK, 2020).
However, there have also been some relatively recent encouraging developments in cancer therapy, which may help to reframe the way cancer treatment is considered and approached. Immunotherapies are attracting increasing interest, making use of the patient's immune system to fight the cancer cells. Some of these therapies, including more novel agents, will be explored here.
CAR-T therapy
First offered to patients in the UK in early 2019, chimeric antigen receptor T-cell (CAR-T) therapy forms part of a newer class of medicines designated advanced therapy medicinal products (ATMPs). During CAR-T therapy, T-cells are removed from the patient's blood and genetically modified before being reinfused back into the patient once the new CAR-T cells have the ability to seek out and destroy the patient's exact type of cancer cells (Chappell, 2020; NHS, 2020).
Chimeric antigen receptor T-cell acting against a cancer cell
Despite it being in its early days, one of the most encouraging aspects of CAR-T therapy is that it is resulting in encouraging disease responses in patients who previously had no treatment options (Chappell, 2020). It is developed for each individual patient, reprogramming their immune cells to target their cancer (NHS, 2020). The NHS (2020) noted that it is potentially risky but has been shown in trials to ‘cure’ some patients, even some with advanced cancers where other treatments have failed. CAR-T therapy can, however, cause severe side effects in some patients, such as high fever, severe low blood pressure, confusion, headaches, seizures, weakened immunity, low blood cell counts and severe infections (Martin, 2020).
At present, the NHS is providing CAR-T therapy for the following patient groups (NHS, 2020):
- Children and young people (up to age 25 years) with B-cell acute lymphoblastic leukaemia
- Adults in England with relapsed or refractory diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma after two or more systemic therapies.
Tumour-agnostic drugs
One of the ways in which cancer takes advantage of a person's immune system is by turning on and off its molecular brakes or ‘checkpoints’ that distinguish between the body's own cells and foreign cells (Martin, 2020). Drugs known as immune checkpoint inhibitors release the brakes, so that the immune system can continue to effectively do its job and attack the cancer cells (Martin, 2020).
An immune checkpoint inhibitor called pembrolizumab targets and blocks the PD-1 protein on the surface of T-cells, again triggering the T-cells to locate and destroy cancer cells (Cancer Research UK, 2019a). Nivolumab blocks a protein that stops the immune system from functioning effectively (Cancer Research UK, 2019b). Both these drugs were approved for specific cancer types, but it has since become clear that patients with a higher number of mutations, regardless of cancer type, benefit the most from these drugs (Gray, 2020).
These drugs are novel in that they are ‘agnostic’ to the type of disease, rather being based on a molecular finding (Gray, 2020). This has paved the way for the possibility of targeted drugs for all cancers with a particular biomarker, regardless of where in the body the tissue originates (Gray, 2020).
In late 2019, larotrectinib became the first medicine developed specifically to target a mutation rather than a tumour type to be licensed for use in Europe, and it is being assessed in the UK by the National Institute for Health and Care Excellence (NICE). This drug, together with entrectinib (also being assessed by NICE), are the newest examples of tumour-agnostic therapies for cancer, and both specifically target the neurotrophic tyrosine receptor kinase (NTRK) fusion mutation, which can lead to abnormal proteins that may cause the growth of cancer cells, regardless of tumour type (Gray, 2020). Both of these drugs received accelerated approval by the US Food and Drug Administration for use in patients with solid tumours that harbour this mutation, but early draft guidance suggests that NICE has found them too expensive to approve on the NHS (Gray, 2020).
There are several theories, beyond cost alone, for why this might be. NICE uses clinical trials to assess drugs; because larotrectinib is a novel option that cannot be organised by tumour type, it makes it difficult to assess by traditional means, and it will probably be more reliant on genetic testing and genomic technologies, which will allow for these and other forms of more personalised treatments and interventions in the long term (Mendes, 2019; Gray, 2020).