Pancreatic cancer is one of the most challenging diseases to treat, and while survival rates have improved since the 1970s, they have plateaued in recent years. But studies show two promising drugs in the pipeline each seem to double survival, reports TIME Magazine.
Revolution Medicines reported last week that its cancer pill, daraxonrasib, helped patients survive an average of 13.2 months after starting treatment, compared with 6.7 months for those receiving standard chemotherapy. “These are dramatic results, with practice-changing outcomes,” said Dr Mark Goldsmith, CEO of Revolution Medicines.
The next day, research supported by another company, Actuate Therapeutics, was published in Nature Medicine showing that the company's pancreatic cancer drug, elraglusib, also doubled one-year survival for patients taking it compared with those getting standard chemotherapy. Elraglusib is given by IV.
Revolution Medicines’ results came from a phase 3 trial, and Goldsmith said the company plans to submit them to the US Food and Drug Administration (FDA) in a request to approve the drug. Revolution Medicines was also the first cancer company to receive a Commissioner’s National Priority Voucher for a cancer drug, which means the FDA will review the application and provide a decision on an expedited timeline.
Actuate’s study is an earlier stage phase 2 trial, and the company plans to continue studying and testing the drug in more patients.
Taken together, the results provide much-needed hope for the pancreatic cancer community, which hasn’t had as many options as patients with other types of cancer.
Immune-based therapies and personalised treatments based on genetic mutations found in a person’s tumour, for example, have not worked well against pancreatic cancer. Despite the seemingly small improvement in survival time, such advances are the first step toward more meaningful benefits for pancreatic cancer patients.
Dr Eileen O’Reilly, a gastrointestinal medical oncologist at Memorial Sloan Kettering Cancer Centre who was involved with the studies on daraxonrasib, said the encouraging findings about daraxonrasib “hopefully set the stage for building on targeted therapy as a major backbone for the treatment of pancreas cancer, and a key goal now is to build and extend these results in all stages”.
Revolution Medicine’s pill daraxonrasib targets mutations in a gene called KRAS, which was the first cancer-causing gene identified and has long been known to contribute to a variety of cancers. The gene controls cell growth, and mutations turn the gene permanently on, leading to abnormal growth.
Daraxonrasib inhibits KRAS activity using a novel way of blocking the KRAS protein, said Goldsmith. “The reason why it’s worth drugging, particularly in pancreatic cancer, is because more than 90% of pancreatic tumours carry a mutation in RAS, which is the larger family of this gene,” he says. “If you’re not trying to inhibit RAS, you’re really not treating the cause of the disease.”
The company’s study included patients with a range of KRAS mutations, all of whom had pancreatic cancer that had spread despite being treated with chemotherapy. The patients in the study took a daraxonrasib pill daily or received standard chemotherapy.
“I’ve already told my colleagues that from today is an inflection point – that if things stay positive, everything should change,” said Dr Wungki Park, a pancreatic cancer specialist at Memorial Sloan Kettering Cancer Centre, who was involved in the early human trials of daraxonrasib.
“There will be pre-daraxonrasib and post-daraxonrasib. This is a really, really good outcome.”
Elraglusib attacks pancreatic tumours a different way, triggering various changes such as slowing tumour growth and making the environment around the tumour more susceptible to treatments like chemotherapy and immunotherapy.
Pancreatic tumours have traditionally not responded well to immunotherapies because the tumours tend to be full of fibrotic tissues that make it difficult for immune cells to infiltrate.
“We started seeing immune-cell infiltration around the tumour when we treated with the drug,” said Dr Devalingam Mahalingam, associate director of clinical research at Northwestern University’s comprehensive cancer centre and lead author of the study.
In the study, those taking elraglusib by IV infusion once a week increased their survival by three months compared with people receiving chemotherapy, and reduced their risk of dying during the study period of about a year by 38%.
“Those results are rarely seen in pancreatic cancer,” said Mahalingam. The study involved people who were recently diagnosed with pancreatic cancer, and therefore probably had the greatest chance of responding to the drug.
But Mahalingam said previous studies of elraguslib in people who had been treated with chemotherapy and experienced recurrences also showed some improvement, although to a lesser degree.
“We are not curing patients, unfortunately, but patients are living longer,” he said. “The goal of this is to give us new targets for therapeutics that may reverse the kinetics or growth of pancreatic tumours.”
The company is currently studying a pill form of the drug, which patients would take once a day like daraxonrasib. The hope is that the daily dose would potentially keep the drug at higher levels in the body, said Mahalingam.
With more promising drug candidates like elraguslib and daraxonrasib, it might be possible to combine them for even greater benefit for patients, he added. Because daraxonrasib targets the genetic mutations driving pancreatic cancer, for example, combining it with elraguslib, which then interferes with the tumour cells’ ability to grow, could lead to enhance survival for patients beyond what’s possible today.
“We will hopefully get pancreatic cancer survival beyond a year on average for most patients,” he said.
Goldsmith said his company was already studying daraxonrasib in patients newly diagnosed with pancreatic cancer, and expects to provide results at the upcoming meeting of the American Association of Cancer Research.
His team is also studying the drug in combination with surgery. “We are investing heavily across all lines of treatment, with multiple compounds and multiple treatment strategies,” he said. “We want to address everybody with pancreatic cancer.”
TIME Magazine article – Two New Drugs Offer Hope for Pancreatic Cancer (Open access)
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