Pancreatic cancer remains one of the deadliest forms of cancer worldwide, with most patients diagnosed only after the disease has already spread. Survival rates have improved little over decades, making breakthroughs in treatment particularly significant. At the recent Annual Meeting of the American Society of Clinical Oncology (ASCO), researchers presented results of a landmark clinical trial of Daraxonrasib, a targeted therapy that has shown unprecedented benefits for patients with advanced pancreatic cancer.
In a chat with India Today, Dr Shubham Pant, a gastrointestinal oncologist at MD Anderson Cancer Center and a co-investigator on the trial, discusses why the findings are being hailed as a major advance, how the drug works, what it means for patients and families, and why this could mark the beginning of a new era in pancreatic cancer treatment. Edited excerpts:
Daraxonrasib has generated considerable excitement in the cancer research community. Why is it being described as a breakthrough for pancreatic cancer?
Dr Pant: Pancreatic cancer is one of the most challenging cancers to treat. Nearly 80 percent of patients are diagnosed at Stage IV, when the disease has already spread to organs such as the liver or lungs. While pancreatic cancer accounts for only about 1-2% of cancer incidence in India, it ranks among the leading causes of cancer-related deaths.
Unfortunately, despite decades of research, survival outcomes have improved very little. For newly diagnosed patients with metastatic pancreatic cancer, average survival is often around a year or less. That’s why the results presented at ASCO were so significant. We genuinely saw something that could change the trajectory of treatment for this disease.
Why is pancreatic cancer usually diagnosed so late?
Dr Pant: The pancreas is located deep inside the body, which makes early detection extremely difficult. Symptoms are often vague and non-specific – indigestion, mild abdominal discomfort, back pain, unexplained weight loss, or fatigue.
By the time more obvious symptoms such as jaundice appear, the disease has often already spread. Unlike breast cancer, where mammograms can help detect disease early, we currently don’t have an effective screening test for pancreatic cancer in the general population.
One of the headline findings is that the drug appears to double survival. How significant is that?
Dr Pant: It’s extremely significant. First, it’s important to understand what Daraxonrasib does. About 90% of pancreatic cancers are driven by a mutation called KRAS. Think of KRAS as a light switch that’s permanently stuck in the “on” position, continuously telling cancer cells to grow. For decades, scientists struggled to target this mutation because the KRAS protein was considered “undruggable.”
Daraxonrasib works by binding to the KRAS protein and effectively turning that switch off, leading to cancer cell death.
In the Phase III trial, called RASolute-302, we studied patients with metastatic pancreatic cancer who had already received one line of chemotherapy. Patients were randomly assigned to receive either standard chemotherapy or Daraxonrasib.
Historically, survival in this setting has been around six months or less. With Daraxonrasib, median survival increased to 13.2 months – more than double.
Beyond survival statistics, what does this mean for patients’ quality of life?
Dr Pant: That’s a crucial question. It’s not only about living longer; it’s about living better.
We assessed patient-reported outcomes during the trial. Patients experienced less pain, improved appetite, weight gain, and better overall functioning.
I remember one patient who loved playing golf but had become largely confined to bed because of pain. Within a month of starting treatment, he was back on the golf course, spending meaningful time with friends and family. Those moments matter enormously to patients.
KRAS mutations are also involved in other cancers. What makes this development important beyond pancreatic cancer?
Dr Pant: KRAS was identified almost 50 years ago, but it remains one of the toughest targets in cancer biology. The protein’s structure makes it very difficult for drugs to bind effectively.
While KRAS is the primary driver in about 90% of pancreatic cancers, it’s also commonly found in lung cancer and colorectal cancer. Daraxonrasib is therefore being studied in these cancers as well.
This breakthrough extends beyond a single disease. It validates KRAS as a target and opens the door to an entirely new generation of therapies.
Q: What are the next steps in the development of Daraxonrasib?
Dr Pant: The trial presented at ASCO focused on patients who had already received prior treatment. Our next goal is to move the drug into the first-line setting.
We’ve launched a global study called RASolute-303, which is evaluating Daraxonrasib alone or in combination with chemotherapy in newly diagnosed metastatic pancreatic cancer patients.
The hope is to bring the benefits of this therapy to patients much earlier in the course of their disease.
Could this drug also help patients diagnosed at earlier stages?
Dr Pant: Potentially, yes.
Patients with Stage I, II, or III disease can often undergo surgery to remove the tumour. After surgery, we typically give chemotherapy to eliminate microscopic cancer cells that may remain.
Even then, about half of patients experience recurrence within five years.
That’s why we’ve launched another study, RASolute-304, which is evaluating Daraxonrasib in earlier-stage disease after surgery. This is where we may have an opportunity not just to prolong survival, but potentially to increase cure rates.
For Stage IV disease, we are improving outcomes significantly, but we are not yet talking about a cure.
Tell us a little about your own journey and how you became involved in the development of this drug.
Dr Pant: My journey began in New Delhi. I grew up in Delhi Cantonment, and my father served in the Indian Army. I studied at Maulana Azad Medical College before moving to the United States for residency and fellowship training.
Today, I specialize in gastrointestinal cancers at MD Anderson Cancer Center. I became involved with Daraxonrasib about three to four years ago during its early clinical development. We treated some of the first patients in Phase I trials and helped evaluate the drug’s activity.
Because of my focus on pancreatic cancer, I became one of the co-investigators on the programme and was fortunate to be a co-author on both the New England Journal of Medicine publication and the ASCO presentation.
There is always a risk that breakthrough drugs get overhyped. How should patients interpret these results realistically?
Dr Pant: That’s an important point. Cancer is not a single disease; it’s more than 300 different diseases. Pancreatic cancer is very different from lung cancer, colon cancer, or breast cancer. Progress in one cancer does not automatically translate to all cancers.
The results with Daraxonrasib are genuinely significant, but it is not a cure for metastatic pancreatic cancer. What it offers is longer survival, better quality of life, and new hope for patients who previously had very limited options.
At the same time, we must continue focusing on earlier detection. If we can identify cancers sooner, before they spread, the chances of cure increase dramatically.
Many Indian patients worry about access to new therapies. What would you say to them?
Dr Pant: Access remains a challenge globally, not just in India. New therapies often take time to become widely available and affordable.
The medical community, industry, and policymakers all need to work together to ensure that promising treatments reach patients faster. For people facing advanced cancer, every month matters.
Looking back 10 years from now, do you think this could be remembered as the beginning of a new era in pancreatic cancer treatment?
Dr Pant: I believe it could be.
I remember when immune checkpoint inhibitors transformed melanoma. Before those therapies, outcomes were extremely poor. Then, almost suddenly, we saw dramatic improvements in survival.
Today, there are around 70 different KRAS-targeted drugs in development. Daraxonrasib is not the only one. What we’re witnessing is the beginning of a much larger wave of innovation.
I often compare it to cracking a dam. This drug may be one of the first major breakthroughs that opens the floodgates for many more effective therapies.
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