In June 2023, Irene Blair, a 59-year-old grandmother from Newark, Delaware, faced a grim prognosis as her pancreatic cancer advanced to stage 4. With a life expectancy of only six to eight months, she turned to a new drug, daraxonrasib, currently under investigation at Penn Medicine’s Abramson Cancer Center. As part of clinical trials, this drug offers a potential lifeline for patients confronting one of the deadliest forms of cancer.
Daraxonrasib belongs to a class of medications known as KRAS inhibitors, which target a critical protein linked to cancer proliferation. Pancreatic cancer presents the highest mortality rate of all cancers, with only 13% of patients alive five years post-diagnosis. Despite not being classified as a cure, the early results from clinical trials indicate a significant breakthrough in treatment options for a disease typically diagnosed at advanced stages.
The urgency surrounding the drug has intensified recently. Former Nebraska Senator Ben Sasse publicly disclosed his diagnosis of metastasized, stage-four pancreatic cancer, highlighting the need for more effective treatments. In light of promising early trial results, the U.S. federal government has expedited the review process for daraxonrasib, which is produced by Revolution Medicines, Inc..
In a phase 1 trial involving 38 patients, daraxonrasib reportedly doubled the survival time for half of the participants compared to standard chemotherapy, increasing it from about seven months to 15.6 months. Mark O’Hara, Blair’s oncologist and leader of multiple trials on KRAS inhibitors at Penn, emphasized the lack of effective therapies for pancreatic cancer beyond traditional chemotherapy.
Blair commenced her treatment in a phase 3 trial in July. Remarkably, within three weeks, her cancer-related pain subsided. Scans in October revealed that her tumors were stable or decreasing, and a December scan confirmed that her cancer had not progressed. Blair, who previously experienced significant weight loss and debilitating weakness due to chemotherapy, now feels much improved, aside from occasional facial rashes.
The ongoing development of KRAS inhibitors has been a long-standing goal in cancer research. Since the discovery of the KRAS protein in 1982, researchers have sought to create a drug capable of blocking its action. These efforts culminated in 2021 with the FDA’s approval of the first KRAS inhibitors for lung cancer. Currently, dozens of such inhibitors are under development, with daraxonrasib being among the first specifically tested for pancreatic cancer, where nearly 90% of cases involve KRAS mutations.
As a pan-RAS inhibitor, daraxonrasib not only targets KRAS but also two related proteins, HRAS and NRAS, that contribute to cancer growth. In another phase 1 trial, over 90% of the 83 participants experienced a halt in cancer progression during treatment, while approximately 30% saw tumor shrinkage. Patients administer the drug daily at home in the form of three pills.
The most common side effect reported is a rash, experienced by 91% of patients in the phase 1 trial, with 8% encountering severe cases. Other side effects include diarrhea, nausea, vomiting, and mouth sores. O’Hara noted that these symptoms are generally manageable with medication, allowing for a better quality of life compared to chemotherapy.
Blair envisions using her additional time to travel and reconnect with family, having retired from her real estate career in May. “You just wonder, ‘Will I be here next year?’” she reflected, highlighting the emotional toll that cancer takes, especially during the holiday season.
As research continues into KRAS inhibitors, the potential for new treatments offers hope not only to Blair but to many others facing similar battles against pancreatic cancer. The journey of daraxonrasib exemplifies the relentless pursuit of advancements in cancer therapy and the promise of improved outcomes for patients worldwide.
