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.
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.