The Medicines and Healthcare products Regulatory Agency (MHRA) has approved a first-of-its-kind cancer drug – capable of targeting a gene mutation that causes some of the most aggressive cancers – to treat a certain form of lung cancer.
The ground-breaking decision follows a 40-year hunt for a drug that can tackle a mutation long considered to be ‘undruggable’.
Sotorasib is one of the most exciting breakthroughs in lung cancer in 20 years.
– Professor Charles Swanton, Cancer Research UK’s chief clinician
The NHS in England will begin to offer the drug within weeks to eligible lung cancer patients, following a national access agreement reached with the manufacturer.
A ‘major breakthrough’ lung cancer drug
Sotorasib (Lumykras) has been licenced to treat adults with non small cell lung cancer that carries a specific genetic fault (known as the KRAS G12C mutation). It will be an option for patients whose tumours have begun to spread and who have already been treated with platinum-based chemotherapy and/or immunotherapy.
Around 600 NHS patients a year in England are expected to benefit from the tablet.
Professor Charles Swanton, Cancer Research UK’s chief clinician, said: “Sotorasib is one of the most exciting breakthroughs in lung cancer in 20 years, targeting a cancer gene that was previously untargetable and built on decades of laboratory research that’s unravelled cancer’s inner workings.”
Around 1 in 4 cancers are driven by faulty RAS proteins. These faults are commonly found in several hard-to-treat cancers, including pancreatic, lung and bowel tumours.
Scientists have spent decades unravelling how KRAS drives cancer growth. This included Cancer Research UK-funded researchers who showed that signals from outside the cell activated KRAS, triggering a cascade of signals inside cells and changing their behaviour.
Despite this knowledge, scientists have struggled to find ways to disrupt KRAS, leading to the long-standing notion that the protein was ‘undruggable’.
But scientists persisted, finding a way to target a specific fault in KRAS (G12C) and paving the way for drugs like sotorasib. In a phase 2 clinical trial – published in The New England Journal of Medicine – 46 of 124 patients had some response to sotorasib.
People taking the drug lived without their tumour growing for 7 months on average. The trial didn’t compare the drug with any currently available treatments, but the researchers noted that those taking standard treatments (chemotherapy) in other trials have lived without their tumour growing for less than 4 months on average.
Treatment-related adverse events occurred in 88 patients, with the most common being diarrhoea, nausea and fatigue.
Swanton said: “This medicine expands our list of effective precision therapies in lung cancer that are helping to improve survival for patients with limited options. It’s great news that patients in England will now benefit from this novel treatment.”
Interim NHS Chief Commercial Officer, Blake Dark, said that after 40 years of scientific research, this drug marks “a major breakthrough in cancer treatment, which is why the NHS has worked to secure rapid access to treatment for hundreds of eligible lung cancer patients”.
Sotorasib was approved through project Orbis – a programme coordinated by the US Food and Drug Administration (FDA) to review and approve promising cancer treatments. It’s the second drug to be approved through project Orbis, which includes the regulatory authorities of Canada, Australia, Switzerland, Singapore, Brazil and, as of January 2021, the UK.
The drug will be available for NHS use within weeks after NHS England, the National Institute for Health and Care Excellence (NICE) and manufacturer Amgen reached an agreement to enable early access to eligible lung cancer patients in England on a budget-neutral basis to the NHS, as NICE completes its ongoing assessment.
Final NICE guidance is expected in March 2022. NICE decisions are usually adopted in Wales and Northern Ireland, while Scotland has a separate process for reviewing drugs.
A late-stage clinical trial comparing sotorasib with docetaxel for adults with non small cell lung cancer that carries the G12C KRAS mutation is set to open soon. Researchers are also investigating if sotorasib could be combined with other treatments for people with advanced tumours that contain the specific KRAS mutation.
Scientists are also looking at alternative ways to target the KRAS mutation. In 2019, the Cancer Research UK Beatson Institute formed a multi-year partnership with Novartis develop new KRAS inhibitors, building on existing work led by the Glasgow institute.
And earlier this year, Cancer Research UK-funded scientists revealed their drug – CCT3833 – could restrict growth of pancreatic, bowel and lung cancer cells carrying KRAS mutations in the lab.
3 March 2022 update: Sotorasib is being recommended by the National Institute for Health and Care Excellence (NICE) for use on the NHS in England within the Cancer Drugs Fund, which helps provide interim access to promising medicines while more data is collected on their clinical benefit.
However, there is some uncertainty in the clinical evidence. Sotorasib has the potential to be cost effective, but further evidence is required to address any uncertainties before it can be recommended for routine use.
So, while sotorasib hasn’t been recommended for routine use in the NHS right now, it is being recommended for use in the Cancer Drugs Fund so that further direct comparative data, long-term evidence and information around cost effectiveness can be collected and reassessed by NICE in the future. Once enough evidence is available, the process for exiting the Cancer Drugs Fund will begin at this point and the review of the NICE guidance will start, expected March 2024.
Over 500 people in England are eligible to receive this treatment in 2022. Drugs approved by NICE for use through the Cancer Drug Fund in England are normally considered in Northern Ireland in line with existing arrangements for endorsement of NICE recommendations. If approved by NICE for routing use on the NHS in England, following further analysis, this decision will likely then be adopted in Wales and Northern Ireland. Scotland has a separate process for reviewing drugs.