Pancreatic cancer almost always comes back. Although the last few years have seen major advances in treatments for this highly fatal cancer, most patients will experience recurrence because today’s standard testing cannot detect lingering microscopic cancer cells.
If there was a way to reveal these cells before cancer took hold again, patients with pancreatic cancer could receive treatment earlier and enjoy a longer lifespan.
Akhil Chawla, a surgical oncologist and pancreatic cancer researcher at Northwestern University, and his team have been working on exactly that. “Our goal is not just to predict who will recur, but ultimately intervene with treatment before recurrence of cancer even shows up on an imaging study,” Chawla told DDN.
In a new paper published in Clinical Cancer Research, his team showed that a sensitive assay measuring circulating tumor DNA (ctDNA) in the blood was able to detect high levels of KRAS mutations — which are present in over 90 percent of pancreatic cancer patients — in very small amounts of ctDNA better than standard sequencing tests. Even when CT scans showed no evidence of cancer, their test found KRAS ctDNA in more than 55 percent of patients.
“These findings suggest that this assay to detect ctDNA could become an important tool for monitoring pancreatic cancer treatment response, identifying patients at high risk of recurrence, and eventually helping guide earlier intervention before recurrence becomes clinically apparent,” said Chawla.
A new blood test to match a new treatment
The new blood test is especially timely given the exciting recent results from Revolution Medicines’ pan-RAS inhibitor daraxonrasib to treat pancreatic cancer. In April, the company announced that their treatment doubled overall survival compared to chemotherapy.
“This blood test is testing for the exact same mutation that daraxonrasib is targeting: KRAS,” said Chawla. “This is where the power of this test could come in. This may offer an opportunity to evaluate if it makes sense to [give daroxonrasib] earlier in the disease course, particularly if patients are becoming resistant to their chemotherapy, potentially increasing the chance for cure.”
Chawla added that the most recent publication from Revolution Medicines’ RASolute 302 Trial showed that most patients still had disease progression while taking daraxonrasib, suggesting that their KRAS-based blood test could be used as a biomarker for response and resistance. “If patients are responding to this drug, this biomarker may be important to understand how long they need to stay on the drug, as daraxonrasib also has known toxicities,” said Chawla.
Since their blood test has greater sensitivity than the standard next generation sequencing, Chawla also said that “we have also been able to show that it’s not just the detection that matters, the burden or quantity of KRAS ctDNA in the blood matters, and we can follow this over treatment.” Patients who are able to clear the ctDNA out of their blood completely do better in terms of survival, he explained.
Blending the blood test with treatment
In the future, Chawla hopes that this new blood test could be used alongside routine imaging. “The ideal scenario is that we stop waiting for cancer to become visible before we act,” he said. Instead, frequent testing could track levels of ctDNA to see if they remain undetectable, which could suggest that the treatment is working, or if it becomes visible or continues to increase, then it could signal microscopic residual disease months before recurrence appears on a CT scan, Chawla noted.
The ideal scenario is that we stop waiting for cancer to become visible before we act.
—Akhil Chawla, Feinberg School of Medicine at Northwestern University
The research team also harbors hope that their blood test could one day be used to screen patients to detect early signs of pancreatic cancer rather than recurrence of disease. To accomplish this, Chawla’s team is actively working on seeing whether they can detect even smaller amounts of KRAS ctDNA in patients who may be at risk of pancreatic cancer but without any signs on imaging.“This is a challenging goal, since most patients with greater risk for pancreatic cancer development, thankfully, do not develop pancreatic cancer. Therefore, we will need to test many many patients to make sure that our false negative and false positive rates are acceptable. We are on the forefront of that research within our lab,” said Chawla.
Chawla’s team is also focused on validating their findings related to the blood test detecting recurrence in larger prospective clinical trials. They plan to study whether therapy can be adjusted based on the ctDNA results.
“Our aim is to individualize each patient’s treatment based on what we are seeing in the blood, rather than giving everyone the same or similar treatment,” said Chawla. “The ultimate goal is to individualize care to improve the outcomes and quality of life for patients with pancreatic cancer.”
