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SAN DIEGO – Experimental treatments with fundamentally different approaches are fueling a wave of optimism that survival rates could improve substantially for pancreatic cancer, one of the most stubbornly malignant forms of the disease.
Giving doctors and patients more options for standard chemotherapy will “increase the number of shots on target” and perhaps make the dreaded diagnosis manageable over many years, according to experts.
Farther along and generating the most excitement is a pill developed by Revolution Medicine, which blocks a protein that drives cancer cells to multiply and form and grow tumors. Phase 3 clinical trial results announced this month showed that patients treated with a new drug called daraxonrasib lived an average of 13.2 months compared to 6.7 months for people who received chemotherapy.
The Food and Drug Administration has put the drug on its fast track for approval, meaning it could be approved this year. Ben Sasse, a former US senator from Nebraska, is taking medication to treat his pancreatic cancer and gave an interview to the New York Times about his experience, sparking public interest.
“We’ve gone from starvation to feasting on this disease,” said Shubham Pant, an oncologist specializing in the treatment of gastrointestinal cancers at the University of Texas MD Anderson Cancer Center. He spoke Tuesday at the American Association for Cancer Research conference session in San Diego, “Turning the Tide in the Fight Against Pancreatic Cancer.”
“Honestly in pancreatic cancer, we’ve never seen these graphs before,” Pant said, showing a slide that charts patient responses to daraxonrasib in the trial.
A second early success gaining attention is an mRNA vaccine, given after surgical removal of a tumor, that trains the immune system to fight pancreatic cancer cells and prevent recurrence. The vaccine, sponsored by BioNTech and Genentech, has been tested in only 16 people in an early-stage study, but the results were strong enough to start a Phase 2 clinical trial with a recruitment goal of 260 people.
“It’s been gloom and doom for a really long time. … Finally we have some reason to be hopeful,” New York University pancreatic cancer researcher Anirban Maitra said at the San Diego conference.
The need for effective pancreatic cancer treatment is urgent as it is the deadliest for survival. It is the third leading cause of cancer death in the United States, with only 13 percent of patients surviving five years, according to the National Cancer Institute. Treatment has changed little over three decades.
“Very, very few pancreatic cancers have tumors that are sensitive to currently available targeted strategies,” said Anna Birkenblit, chief medical officer of the Pancreatic Cancer Action Network. The new development will allow doctors to consistently use different treatments and increase the chances of prolonging patients’ lives, she added.
A big reason for the lack of progress so far is that a special protein called KRAS, which pancreatic cancer cells need to proliferate, has a smooth surface, making it difficult for drugs to bind to it and disrupt growth. Revolution Medicines found a way around the problem by developing a compound that acts like molecular glue, blocking KRAS growth signals.
“KRAS inhibitors are game changers. … This is a new era. We’re really starting to see responses, and we can build on it,” said Elizabeth Jaffee, deputy director of Johns Hopkins’ Sidney Kimmel Comprehensive Cancer Center, which works to develop immunotherapies for pancreatic cancer. “I’ve been doing this for over 30 years. … For me, as someone who cares for these patients and my colleagues, we’re extremely excited.”
Jaffee cautioned that the results of mRNA immunotherapy from BioNTech and Genentech come from very small trials. The National Cancer Institute is planning a major initiative focused on overcoming obstacles to cancer vaccines, and Jaffee said pancreatic cancer is one of the types being discussed as a potential target. His own lab is working on immunotherapy using long peptides.
“We need to improve 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”, said Jaffee.
Despite no drug on the market, Revolution Medicines’ stock price rose more than 50 percent on April 13, the day the Phase 3 trial results were announced. The company is making progress on several fronts with four drugs targeting the RAS in clinical development. Its researchers are trying to learn more about how patients develop resistance to treatment.
“We don’t see this as the end of the game. We’re moving through one inning of a very difficult game,” Mark Goldsmith, chief executive of Revolution Medicines, said in an interview.
The most conclusive data so far comes from a large trial that extended life in people who tried daraxonarasib after other treatments failed to help. But many in the field are eagerly awaiting the results of 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 that showed evidence of antitumor activity in combination with chemotherapy and by itself, as a first-line therapy for pancreatic cancer patients.
Regarding side effects, in previous trials, 95 percent of patients reported an undesirable reaction and 35 percent suffered severely, according to the company. The most common side effect is skin rash, which is usually mild.
There are other approaches in development that are also providing exciting early results. Jaffee said she is looking closely at “degraders,” drugs that destroy the mutated RAS protein.
She said one of the main issues researchers are debating is how to get KRAS inhibitors to patients more quickly.
“With drugs this extraordinary, do we really need to do a randomized, phase 3?” Jaffee said. “Many patients with pancreatic cancer died without access to this drug.”
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