A “game-changing” daily pill helped almost double survival time for patients with the most deadly major cancer.
Pancreatic cancer patients on the drug lived for twice as long as those on chemotherapy. The pill’s success is thought to be the biggest leap forward in the fight against this lethal form of the disease for decades.
And experts at the world ’s largest cancer conference said the drug could extend the life expectancy of millions more patients with other types in the future. Speaking at the American Society of Clinical Oncology’s (ASCO) annual meeting in Chicago, one leading medic said the results left her in tears.
Dr Rachna Shroff, ASCO expert in gastrointestinal cancer, described the pill as a “game-changer”. She added: “I don’t know that we use that word very commonly in the world of pancreatic cancer.
“When the press release came out for this data, I was in clinic and, having treated pancreatic cancer for 16 years, I actually started crying. This is such an incredibly impactful study for our patients.”
Dr Julie Gralow, ASCO’s chief medical officer, delivered her verdict with a sports metaphor. She said: “I’ve heard this study described as a home run. I would actually say it’s a grand slam (the maximum-scoring hit in baseball).”
View 2 ImagesPancreatic cancers are generally diagnosed late(Image: Getty Images)
Pancreatic is one of the most feared cancers of all. Three quarters of all adults diagnosed in the UK die within one year. Half die within three months. It is often caught at a late stage, when it has already spread and then has a five-year survival rate of just 3%.
Harry Potter actor Alan Rickman died of the disease aged 69 in January 2016, just five months after being diagnosed. It also claimed the life of Dirty Dancing star Patrick Swayze in September 2009, aged 57.
The drug, daraxonrasib, targets the mutated KRAS gene, which is found in more than nine in 10 pancreatic tumours and causes cells to grow uncontrollably.
Dr Shroff said: “The idea of targeting KRAS has always been the Holy Grail in most malignancies, but specifically in pancreatic cancer because it is nearly ubiquitous and it is an early driver of pancreatic cancer growth.”
Anna Jewell, director of services, research and innovation at Pancreatic Cancer UK, said treatments counteracting these mutations were “some of the most exciting developments we have seen in pancreatic cancer for a very long time”.
She added: “Patients were given months more precious time with their loved ones. Crucially, these results suggest that daraxonrasib is able to keep the cancer under control for longer.”
Ms Jewell called for action to ensure patients can join drug trials in the UK, and for new treatments to be fast-tracked for approval. She added: “Tragically, half of all people with pancreatic cancer die within just three months of their diagnosis.
“More time with those we love most is truly priceless. We must do everything possible to ensure the most promising new treatments are available here in the UK.”
The study involved 500 patients with advanced pancreatic cancer that had spread to other organs. All had previously been treated with chemotherapy. At this stage, the disease is usually terminal.
The trial’s chief investigator Dr Brian Wolpin, from the Dana-Farber Cancer Institute in Boston, said: “Standard chemotherapy in patients who have already received one prior line [of treatment] really does not work as well as we would like.”
The participants were randomly assigned to receive either daraxonrasib or chemotherapy. Those on the new drug survived for an average of 13.2 months after their diagnosis, compared with just 6.7 months among those who had chemotherapy. Patients taking the pill also suffered fewer serious side effects.
Dr Shroff, who leads the division of oncology at the University of Arizona Cancer Center, said the doubling of survival times and a 60% lower risk of death during the trial for patients taking the pill were “not numbers that we typically see. These results are landscape-changing…The RAS revolution is here.”
Daraxonracib targets a family of genes known as RAS, which includes KRAS. Mutations in RAS genes have been linked to one in five of all cancers. Experts hope daraxonrasib could therefore also dramatically boost survival times for other common cancers. It is already in clinical trials for non-small cell lung cancer and colorectal cancer.
Dr Gralow said: “It’s a game-changer. RAS is a very common mutation in cancer so it’s clear it’s going to have a role in lung, colon and pancreatic for sure and then probably beyond.”
Paula Hanford, chief executive of Pancreatic Cancer Action, said: “This is one of the most significant developments we have seen in pancreatic cancer treatment for many years. For far too long, people diagnosed with pancreatic cancer have had incredibly limited treatment options and survival rates that have remained devastatingly low.
“To see a trial showing the potential to nearly double survival time in advanced pancreatic cancer is hugely encouraging and gives real hope to patients and families facing this disease.”
Mr Hanford said more work was needed before the treatment could become available in the UK, but added: “This marks a potentially transformative moment in the future of pancreatic cancer care and underlines why continued investment in research is so critical.”
Dr Samuel Godfrey, Cancer Research UK’s research information lead, said: “Although survival has improved for many cancers over the past few decades, pancreatic cancer has not seen the same gains, in part because it is often diagnosed at a late stage. A treatment that could double survival in this disease would be unprecedented.
“As well as causing fewer side effects than standard chemotherapy, daraxonrasib has the potential to give people with this type of pancreatic cancer more precious time with their loved ones. However, more trials will be needed before we know whether it should be approved for routine use.”
Neville Menezes, consultant pancreatic surgeon at Ashford and St Peters Hospital NHS Foundation Trust, said targeted gene therapies were “the future way forward for treatment of most cancers”.
He added: “Pancreatic cancer patients would benefit significantly because most therapies until today have achieved very little success in pancreatic cancer. There are multiple facets available to use this approach and every single day something new is coming up.
“We have to all hope that we will not have to wait for too long to implement this gene targeted approach to treat our patients. It is already being implemented in some centres over the world under the umbrella of a trial.”
The human body contains a family of genes called RAS — including its most notorious member, KRAS.
These genes code for proteins that act like a light switch, flipping on when the body needs to grow or repair tissue and turning off when the job is done. When a RAS gene mutates, the switch becomes stuck in the “on” position, causing cells to grow uncontrollably.
The mutated KRAS protein is smooth and seemingly impenetrable, so scientists nicknamed it the “Death Star” after the Star Wars superweapon.
KRAS mutations are implicated in 90% of pancreatic cancer cases. It was considered “undruggable” for decades, but daraxonrasib is able to latch onto RAS proteins and turn the metaphorical switches back off.
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The trial found the drug worked just as well in patients who did not have a mutation because daraxonrasib acts on both mutant and normal forms of RAS. Shutting down normal RAS proteins can still help to stop a patient’s cancer from growing.