Pancreatic cancer is a dreaded diagnosis - it is often detected late and then the chances of survival are poor. A new drug offers hope for people with the disease at an advanced stage. The drug daraxonrasib does not promise a cure, but is intended to prolong survival compared to chemotherapy. The European Medicines Agency (EMA) now recommends approval in the EU for adults with pancreatic cancer with metastases who have already had at least one previous treatment. The authority tested the active ingredient with the trade name “Rasonque” in an accelerated procedure.
What is the new drug about?
Daraxonrasib is an active ingredient against tumors in which a specific cell control protein is permanently active. In a phase III study with 500 patients with advanced pancreatic cancer, those affected who received the drug lived a median of 12.4 months, according to the EMA. In the comparison group with chemotherapy it was 6.7 months. All patients had already completed a first round of chemotherapy. With the new drug they lived for 7.2 months without deterioration, and with chemotherapy they lived for 3.6 months.
“The drug is a “game changer” in the fight against pancreatic cancer, not just for the now approved indication,” said the President of the German Cancer Society (DKG), Thomas Seufferlein, to the dpa.
How common is pancreatic cancer in Germany?
It is one of the most common cancers of the gastrointestinal tract. According to the Cancer Information Service and the Robert Koch Institute (RKI), around 20,000 people in Germany develop pancreatic cancer every year. This makes the number significantly smaller than for breast or prostate cancer, but the disease is particularly dangerous.
Why is the prognosis so unfavorable?
For a long time, pancreatic cancer causes no or only unspecific symptoms such as weight loss or pain in the upper abdomen or back. The tumor is therefore often discovered late, often only when it has already spread. This is why this type of cancer is fatal for most sufferers within a short period of time. Only about one in ten people are still alive five years after diagnosis, according to cancer registry data from the RKI. The disease usually occurs over the age of 70.
What chances of recovery are there?
A cure is currently only possible if the tumor is discovered early and can be completely removed surgically. This only affects a small proportion of those affected. For metastatic pancreatic cancer, treatment is palliative. The aim is to extend survival time and maintain quality of life. If the disease progresses after initial therapy, the options are currently limited. “Daraxonrasib opens a window for new therapeutic options in combination with the substance,” said Matthias Ebert from the German Society for Gastroenterology, Digestive and Metabolic Diseases of the dpa.
How does daraxonrasib work?
Daraxonrasib belongs to a new class of drugs called RAS(ON) inhibitors. RAS is a so-called proto-oncogene. It contains the building instructions for a protein that triggers growth and division processes in cells. Normally, this protein is only active temporarily and switches itself off again. Due to mutations, it remains permanently active and promotes tumor growth. "Then it's like stepping on the accelerator pedal. Then the signal path is active all the time," explains Ebert. Such mutations are present in around 90 percent of pancreatic cancer cases.
Daraxonrasib inhibits the interaction of the RAS protein with downstream signaling pathways. Ebert compares this to a ball that is placed behind the accelerator pedal so that it can no longer be depressed. Unlike previous inhibitors, the new drug works not only against a specific mutation, but also against different RAS variants.
What side effects occur?
Side effects occurred in all patients; skin rash, diarrhea and inflammation of the oral mucosa were common. Serious side effects occurred less frequently (61.8 percent) than with chemotherapy (69.6 percent). Treatment discontinuations were only 1.2 percent compared to 11.2 percent. There were no life-threatening side effects.
When will the drug be available?
The drug has been approved in the USA since the end of August for adults with metastatic pancreatic adenocarcinoma who have already had their first chemotherapy treatment. It is still unclear when it will be available in Germany. Many patients have already asked about it, says Ebert, who researches tumor diseases of the digestive tract at the Mannheim Medical Faculty at Heidelberg University.
How quickly the drug can actually be used in Germany now depends on the EU. Following the recommendation of the EMA, the European Commission must grant official market approval.
Could the drug also help with other diagnoses?
According to Ebert, some lung cancers and about half of all colon cancers also have the same mutation. Studies are underway on the active ingredient in other types of cancer, but no results are available yet.
Daraxonrasib is not the first targeted cancer drug to attack so-called growth driver genes. According to Ebert, similar medications already work on certain lung tumors.
