Why these treatments for one of the deadliest cancers are stirring such hope
SAN DIEGO — Experimental treatments with radically different approaches are generating a wave of optimism that survival rates for pancreatic cancer, one of the disease’s most stubbornly deadly forms, could improve dramatically.
Giving doctors and patients more options over standard chemotherapy will “increase shots on target” and perhaps even make the dreaded diagnosis manageable within a few years, experts say.
What goes the furthest and is generating the most excitement is a pill developed by Revolution Medicines that blocks a protein that signals cancer cells to multiply and drives tumor formation and growth. Phase 3 clinical trial results announced this month showed that the average survival rate for patients treated with the new drug, called daraxonrasib, was 13.2 months, compared to 6.7 months for people receiving chemotherapy.
The Food and Drug Administration has put the drug on the fast track for approval, meaning it could be approved this year. Ben Sasse, a former U.S. senator from Nebraska, uses the drug to treat pancreatic cancer and sparked public interest by giving an interview to the New York Times about his experience.
“We’ve gone from famine to feast in this disease,” said Shubham Pant, an oncologist at the University of Texas MD Anderson Cancer Center who specializes in the treatment of gastrointestinal cancers. He spoke Tuesday in San Diego at the American Association for Cancer Research conference session titled “Turning the tide in the fight against pancreatic cancer.”
“To be honest, we’ve never seen these graphs before in pancreatic cancer,” Pant said, showing a slide showing patients’ responses to daraxonrasib in a trial.
A second notable early breakthrough is an mRNA vaccine administered after surgical removal of tumors that trains the immune system to fight persistent pancreatic cancer cells and prevent recurrence. The vaccine, sponsored by BioNTech and Genentech, was tested in just 16 people in an early-stage study, but the results were strong enough to launch a Phase 2 clinical trial with a goal of recruiting 260 people.
“It’s been gloom and doom for a really long time… We finally have some reason to be optimistic,” Anirban Maitra, a pancreatic cancer researcher at New York University, told the San Diego conference.
The need for effective pancreatic cancer treatment is acute as it is the deadliest type of cancer in terms of survival. It is the third leading cause of cancer deaths in the United States, with only 13 percent of patients having a five-year survival rate, according to the National Cancer Institute. Treatments have changed little in three decades.
“A very, very small number of pancreatic cancers have a tumor that is susceptible to currently available directed strategies,” said Anna Berkenblit, chief medical officer of the Pancreatic Cancer Action Network. He added that new developments increase the possibility that doctors will be able to administer different treatments in succession and significantly extend a patient’s life.
A big reason why progress hasn’t been made until recently is that the special protein that pancreatic cancer cells need to spread, called KRAS, has a smooth surface, making it difficult for drugs to bind to it and inhibit growth. Revolution Medicines has found a way to solve this problem by developing a compound that works like molecular glue and forms a complex that blocks KRAS growth signals.
“KRAS inhibitors are a game changer. … This is a new era. We’re really starting to see responses and we can build on that,” said Elizabeth Jaffee, associate director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, which is working on the development of immunotherapies for pancreatic cancer. “I’ve been doing this for over 30 years… As someone who cares for these patients and my colleagues, we’re extremely excited.”
Jaffee cautioned that the mRNA immunotherapy results from BioNTech, Genentech and Memorial Sloan Kettering Cancer Center 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 pancreatic cancer is one of the types being discussed as a possible target. His laboratory works on immunotherapy using long peptides.
“We need to develop these platforms so they can do a better job of stimulating the types of T cells that lead to long-term memory responses in the immune system,” Jaffee said.
Even though there was 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 making progress on multiple fronts with four drugs targeting RAS in clinical development. Researchers are trying to learn more about how patients develop resistance to treatment.
“We’re not looking at these as the end game. We’re at the beginning of a very difficult game,” Mark Goldsmith, chief executive of Revolution Medicines, said in an interview.
The most conclusive data so far comes from the large study in which people who tried daraksonrasib extended their lives after other treatments failed to help them. But many in the field are eagerly awaiting the results of a trial testing the drug as a first-line treatment option.
At the American Association for Cancer Research meeting, the company presented data Tuesday showing there is evidence of antitumor activity when combined with chemotherapy and alone as a first-line treatment for pancreatic cancer patients.
In terms of side effects, in a previous trial, 95 percent of patients reported an adverse reaction and 35 percent experienced a severe reaction, according to the company. The most common side effect is skin rash, which is usually not debilitating.
There are other approaches that are providing exciting early results in development. Jaffee said he is closely monitoring “disruptors,” or drugs that destroy the mutated RAS protein.
He said one of the main issues researchers are discussing is whether there is a way to get KRAS inhibitors to patients even faster.
“Do we really need to do a randomized Phase 3 when the drugs are so exceptional?” Jaffee said. “Many patients with pancreatic cancer died before they had access to this drug.”
This story has been updated to note the academic institution involved in the Phase 1 mRNA vaccine trial.
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