SAN DIEGO — Experimental therapies with radically different approaches are stirring a wave of optimism that survival rates could substantially improve for pancreatic cancer, one of the most stubbornly lethal forms of the disease.
Giving doctors and patients more options to standard chemotherapy would “increase shots on goal” and perhaps even make the dreaded diagnosis manageable over a number of years, according to experts.
The furthest along and generating the most excitement is a pill developed by Revolution Medicines, which inhibits a protein that signals cancer cells to multiply and drives tumor formation and growth. Phase 3 clinical trial results announced this month showed patients treated with the new drug, called daraxonrasib, had median survival of 13.2 months compared to 6.7 months for people receiving chemotherapy.
The Food and Drug Administration has put the drugon it’s speediest track for approval, meaning it could be approved this year. Ben Sasse, the former U.S. senator from Nebraska, is taking the drug to treat his pancreatic cancer and gave an interview to the New York Times about his experience, elevating public interest.
“We have moved from famine to feast in this disease,” said Shubham Pant, an oncologist who specializes in treating gastrointestinal cancers at the University of Texas MD Anderson Cancer Center. He spoke in San Diego on Tuesday at an American Association for Cancer Research conference session entitled, “Turning the tide in the fight against pancreatic cancer.”
“Honestly in pancreatic cancer, we have never seen these graphs before,” Pant said, showing a slide that charted patient responses to daraxonrasib in a trial.
A second early breakthrough capturing attention is an mRNA vaccine, given after surgical removal of tumors, which trains the immune system to fight lingering pancreatic cancer cells and stave off recurrence. The vaccine, sponsored by BioNTech and Genentech, has only been tested in 16 people in an early-phase study, but results were strong enough to launch a Phase 2 clinical trial with a recruitment goal of 260 people.
“It’s been gloom and doom for a really long time. … We have some cause for optimism, finally,” Anirban Maitra, a pancreatic cancer researcher at New York University, said at the San Diego conference.
The need for effective pancreatic cancer treatment is acute as it is the deadliest in terms of survivability. It’s the third-leading cause of U.S. cancer deaths, according to the National Cancer Institute, with five-year survival of just 13 percent of patients. Treatments have changed little for three decades.
“Very, very few pancreatic cancers have a tumor that is susceptible to the currently available directed strategies,” said Anna Berkenblit, chief medical officer of the Pancreatic Cancer Action Network. New developments raise the prospect that doctors could deploy different treatments consecutively and substantially prolong a patient’s life, she added.
A big reason for the lack of progress until recently is that the particular protein that pancreatic cancer cells need to spread, called KRAS, has a smooth surface, making it difficult for drugs to bind to it and disrupt growth. Revolution Medicines devised a way around the problem by developing a compound that works like molecular glue, forming a complex that blocks KRAS growth signals.
“KRAS inhibitors are the game changers. … It’s a new era. We’re beginning to really see responses, and we can build on this,” said Elizabeth Jaffee, deputy director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, who works on developing immunotherapies for pancreatic cancer. “I’ve been doing this for over 30 years. … To me, as someone who takes care of these patients and my colleagues, we’re just extremely excited.”
Jaffee cautioned that the mRNA immunotherapy results from BioNTech and Genentech were from a very small trial. The National Cancer Institute is planning a major initiative focused on overcoming hurdles in cancer vaccines, and Jaffee said that pancreatic cancer is one of the types that have been discussed as a possible target. Her own lab is working on immunotherapy using long peptides.
“We need to improve on these platforms, so that they do a better job of inducing the types of T cells that lead to long-term memory responses” in the immune system, Jaffee said.
Even with no drug on the market, Revolution Medicines’ stock price rose more than 50 percent in the days after it announced Phase 3 trial results on April 13. The company is moving forward on multiple fronts, with four drugs targeting RAS in clinical development. Its researchers are trying to learn more about how patients develop resistance to the treatment.
“We don’t look at these as the end of the game. We are moving through an inning of a very difficult game,” Mark Goldsmith, Revolution Medicines’ chief executive, said in an interview.
The most conclusive data so far comes from the large trial that extended the lifespans of people who tried daraxonrasib after other treatments failed to help them. But many in the field are eagerly awaiting the results from a trial that tests the drug as the first line of therapy.
At the American Association for Cancer Research meeting, the company presented data Tuesday showing that as a first-line therapy for pancreatic cancer patients, there was evidence of antitumor activity when combined with chemotherapy and by itself.
In terms of side effects, in a previous trial, 95 percent of patients reported an undesirable reaction and 35 percent suffered a severe one, according to the company. The most common side effect is a skin rash, which generally wasn’t debilitating.
There are other approaches in development that are also providing exciting early results. Jaffee said she is closely watching “the degraders,” drugs that destroy the mutated RAS protein.
She said that one of the main issues researchers are debating is whether there is a way to get KRAS inhibitors to patients even faster.
“With drugs this exceptional, do we really need to do a randomized, Phase 3?” Jaffee said. “Many patients with pancreatic cancer died before they got access to this drug.”
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