Patients Opting for Experimental Treatment Over Chemotherapy

Every patient with advanced pancreatic cancer who visited Dr. Zev Wainberg expressed a preference for an experimental treatment over enduring another round of chemotherapy.

Wainberg, co-director of UCLA Health’s GI Oncology Program, is overseeing a clinical trial for a new drug named daraxonrasib. Notably, all participants had undergone chemotherapy that was losing its effectiveness.

“Statistically, only half of them actually receive the pill, and we don’t get to choose,” Wainberg explained. “I assigned many patients to the chemotherapy group, and none of them survived.”

He described the experience as one of the most emotional studies he’s been involved in.

The excitement surrounding daraxonrasib is intensifying. In a phase 3 trial with 500 patients, this drug demonstrated the ability to double survival times in those with advanced pancreatic cancer—averaging 13.2 months compared to just 6.7 months for those receiving chemotherapy. Wainberg and his colleagues shared these findings at the annual meeting of the American Society of Clinical Oncology in Chicago, with the complete study published simultaneously in a respected journal.

When the drug’s preliminary results were announced in April by Revolution Medicines, Dr. Rachna Shroff from the University of Arizona Cancer Center expressed overwhelming joy, saying, “It feels transformative for those of us treating pancreatic cancer. It’s unprecedented.”

The enthusiasm is also expanding to other cancer types. Daraxonrasib is administered as three pills daily and targets a mutation in the KRAS gene, prevalent in various cancers, including lung and colorectal types.

Dr. Brian Wolpin, leading research on daraxonrasib and director of the Hale Family Center for Pancreatic Cancer Research at Dana-Farber Cancer Institute, noted, “While pancreatic cancer may be the first, there will undoubtedly be more.” He feels the gates are swinging wide open.

The FDA has already accelerated the approval process for this drug for pancreatic cancer and has allowed Revolution Medicines to provide it to patients outside clinical trials through an expanded access program.

Dr. Mark Goldsmith, the CEO of Revolution Medicines, couldn’t specify when they would seek FDA approval, stating that their team is working tirelessly to prepare the necessary materials.

Shrinking Tumors

Many pancreatic cancers are diagnosed at advanced stages where surgical options are no longer viable.

“The best chemotherapies we have offer only about six months of benefit, and sometimes just weeks,” remarked Dr. Sameek Roychowdhury from Ohio State University Comprehensive Cancer Center. “It’s hardly enough time for families to adjust.”

Statistically, only about 3% of patients diagnosed with metastatic pancreatic cancer will survive five years, according to the American Cancer Society.

Debby Orcutt, 71, was diagnosed with stage 4 pancreatic cancer in April 2024, with the disease already spreading to her liver. Before her diagnosis, she had only experienced worsening pain in her lower left abdomen.

Once chemotherapy began to fail, she joined the clinical trial for daraxonrasib, receiving the drug itself. After starting treatment in January 2025, the spot on her liver has disappeared, and her pancreatic tumor has shrunk by 80%, according to her oncologist.

“I feel great every single day,” Orcutt, from Spencer, Massachusetts, stated. “I don’t focus on my diagnosis.”

Although Roychowdhury and Shroff weren’t involved in daraxonrasib trials, they are actively preparing lists of patients for when the drug becomes publicly available.

Shroff expressed confidence in the drug’s future availability, stating, “Once it’s available, I will absolutely start using it.”

Understanding Daraxonrasib

Daraxonrasib is designed to target a mutation in the KRAS gene, which functions like a control switch for cellular growth. This mutation, found in over 90% of pancreatic cancers, locks the switch in the “on” position, leading to uncontrolled cell growth.

Scientists have been aware for years that targeting this mutation could help reset that switch. However, developing a drug for it has proved challenging. Wolpin described the KRAS protein as a difficult target, but noted recent advancements in chemistry have enabled this breakthrough.

Daraxonrasib is the first drug of its kind to act as a “molecular glue,” binding with a protein inside cells to target the mutated KRAS protein.

While not a definitive cure, daraxonrasib shows promise for extending life. As patients can develop resistance, oncologists aim to have a range of drugs like this available for treatment.

Revolution Medicines has three additional RAS inhibitors in clinical trials, with another due to enter trials soon.

Interestingly, the drug appears beneficial even for patients without the KRAS mutation. The average survival rate for patients receiving daraxonrasib is also around 13.2 months.

“Given what we know, I feel this drug is important for all advanced pancreatic cancer patients,” Wolpin noted. “This shows that we can start reducing our reliance on chemotherapy.”

Currently, chemotherapy remains the standard initial treatment for those with advanced pancreatic cancer, though ongoing research is investigating whether patients should receive daraxonrasib sooner.

In terms of toxicity, daraxonrasib is reportedly less harmful than traditional chemotherapy. Some patients reported mild side effects like upset stomach and rashes, while others experienced more significant reactions. Former senator Ben Sasse likened his rash from the trial to “nuclear,” as he shared in a podcast.

Debby Orcutt mentioned minimal side effects, noting only a small rash and a sore in her mouth, adding, “We’re talking about life or death here. How can I complain about a little rash?”

Orcutt and her husband Ron, who have been together for nearly 50 years, met as teenagers working part-time jobs. Their lighthearted interactions maintain a youthful spirit.

Ron tracks Debby’s daily dosage of daraxonrasib closely, making sure she takes it on an empty stomach at the right times, often setting alarms as reminders. Debby keeps busy, helping her grandchildren and working a part-time job at a local high school, despite not needing the income.

“You’ve just got to keep going and have faith,” she advised. “Everyone has to live each day as if it’s their last. I feel like I’ve been granted a second chance, and I want to make the most of it.”