Every once in a while, an advance in treating cancer is so stunning that doctors get chills. Such is the case for Revolution Medicines' pancreatic cancer therapy daraxonrasib, which in a late-stage study allowed patients with advanced disease to live twice as long as those who only received chemotherapy.
That's an astounding advance for a cancer where experimental treatments have tended to offer progress measured in days or weeks, if at all. Giving patients and their families more months of time together -- another birthday, another Christmas, a family reunion -- would be truly meaningful.
It also lays a foundation for the entire field of researchers and drug developers to build from: What if instead of adding months to someone's life, future progress allows doctors to realistically talk about years?
Pancreatic cancer, which is among the deadliest common cancers, has been infuriatingly difficult to crack. Novel treatments that looked promising in early studies have failed when tested in larger ones.
The challenge comes from how late the disease is discovered -- some 80% of pancreatic cancer patients' tumors have already spread by the time of diagnosis. That makes their cancer inoperable. Previous experimental treatments have tended to briefly shrink tumors at best.
Daraxonrasib is different, experts tell me. The glimmer of hope it generated in smaller trials has grown into a beacon for the field. In a large, carefully designed trial that enrolled people whose disease had progressed despite chemotherapy treatment, patients who received the drug lived 13.2 months, compared to just 6.7 months for those on chemo alone.
That result has stunned pancreatic cancer specialists. Manuel Hidalgo, the director of NYU Grossman School of Medicine's Gastrointestinal Cancer Center, put it bluntly: "This is the most important clinical trial data in pancreatic cancer, ever."
The drug's effect was so unexpected that Wungki Park, a Memorial Sloan Kettering Cancer Center oncologist who was involved in the clinical trial, told me that he's gotten goosebumps while reviewing his patients' responses to the drug.
Park sees this drug as the start of a new chapter in pancreatic cancer treatment: one where doctors have more to offer their patients than just chemo, and researchers get better and better at designing treatments that can shut down these tumors.
That starts with digging into the nitty-gritty details of the data on daraxonrasib. So far, everything the public knows about the study comes from a company-provided press release, but oncologists will get much more information when more comprehensive results are presented at an upcoming cancer conference.
They hope to learn whether certain patients benefited most from the drug -- in particular, if people whose cancer harbors specific mutations improved more; if its efficacy differs depending on where someone's cancer has spread or the kind of chemo they had before receiving it; and if some patients are more prone to its more challenging side effects.
But the work extends far beyond those data. There should be an enormous push to improve upon these results -- not only for this drug, but whatever comes after it. "There are thousands of questions," Hidalgo says. "There are many years of work ahead of us."
Among the most pressing: Could this drug offer even more promise if used in people who are newly diagnosed with pancreatic cancer? The current results are from a study that tested daraxonrasib in people whose disease had progressed after chemotherapy. But using an effective treatment earlier typically leads to better outcomes.
Revolution has run small trials testing the drug alone and in combination with chemotherapy in newly diagnosed patients, and is already conducting a larger trial to provide an answer. Yet given the strength of the current data and the dearth of options for pancreatic cancer, doctors are expected to try it out in newly diagnosed patients once the drug is on the market. (That approval could come soon: Revolution's CEO Mark Goldsmith told me the company is moving as quickly as possible to get daraxonrasib through the regulatory process, which should be hastened by a new Food and Drug Administration voucher program that promises reviews in as little as one to two months.)
Another important question is how to mitigate the drug's side effects. Daraxonrasib works by shutting down a family of notorious cancer-causing proteins, yet it affects healthy forms of those proteins, too. As a result, patients can experience things like rashes and gastrointestinal issues.
For some, those side effects can be intense. Last week, the New York Times talked to former Nebraska Senator Ben Sasse, who last fall was diagnosed with pancreatic cancer that, by the time it was detected, had already morphed into five different forms of cancer. Sasse enrolled in a clinical trial of daraxonrasib, which he has said seems to be working to shrink his tumors.
Yet he's also experienced visible facial bleeding. It’s a side effect Sasse seems to be taking in stride, but when the drug becomes widely available, oncologists will want to learn who is most at risk and figure out the best ways to manage it.
The bigger hope is that daraxonrasib is just the start. The drug has already taught the field that powerfully suppressing this key cancer driver actually works. Now, researchers and oncologists need to throw their brainpower into understanding how to do that even better, whether with this drug paired with others or with the next wave of treatments.