Economic Observer reporter Zhang Ying

Pancreatic cancer is known as the "king of cancer". This is a highly difficult cancer to treat, with a 5-year survival rate of less than 10%, ranking last among all cancers in the long term.

April 15-21 is National Cancer Prevention and Treatment Week, and this year's theme is early screening, early diagnosis, and early treatment. Early screening, early diagnosis and early treatment are particularly important for the prevention and control of pancreatic cancer. Li Zhao, Director of Hepatobiliary Surgery Department of Peking University People's Hospital, receives newly diagnosed patients with pancreatic cancer almost every month, most of whom come to see a doctor at an advanced stage.

"It is difficult to cure any cancer if it is discovered late, and pancreatic cancer is the most difficult type of cancer to be discovered." Li Zhao suggested that patients with recurrent chronic pancreatitis, people with a family history of pancreatic cancer, diabetes patients who suddenly have unexplained blood glucose abnormalities, etc., should regularly take the initiative to do enhanced CT or magnetic resonance imaging of the pancreas.

According to the national cancer report released by the National Cancer Center in 2024, there will be about 119000 new cases and 106000 deaths of pancreatic cancer in China in 2022.

For a long time, the treatment of pancreatic cancer has been very limited. On the eve of Cancer Prevention Week, a new drug for pancreatic cancer developed by Revolution Medicine, an American pharmaceutical company, released phase III clinical data: for patients with metastatic pancreatic cancer who had previously received treatment, the median total survival time of patients using the new drug reached 13.2 months, while that of patients in the chemotherapy group was only 6.7 months.

Although the drug has not been clinically tested in China, many Chinese doctors are excited by this data, and the drug may rewrite the treatment pattern of pancreatic cancer in the future. In an interview on April 15th, Li Zhao also interpreted this new drug.

|Dialogue|

Patients are often in the late stage when they seek medical attention

Economic Observer: Why is pancreatic cancer called the "king of cancer"?

Li ZhaoThe overall incidence rate of pancreatic cancer is not high, but the mortality rate is the highest. The high mortality rate is not due to its high malignancy - one of the main reasons for the high mortality rate after discovery is that it is discovered too late, and any cancer discovered too late is difficult to treat.

The pancreas is located in the retroperitoneal position, with the stomach blocking it in front, making it difficult to see clearly during routine physical examinations (such as ultrasound); The symptoms of early and middle stage pancreatic cancer are also atypical, that is, ordinary weight loss, etc., which is often metastasized when found. In addition, pancreatic cancer is insensitive to many treatment schemes, and even if it is removed surgically, it may also metastasize quickly.

At present, the research on the biological mechanism of pancreatic cancer is not as deep as that of other tumors. Why do some early patients in clinical practice have multiple liver metastases after one or two months of clean surgical resection? Perhaps tumor cells have been lurking in other places through lymphatic fluid or blood for a long time, but they cannot be detected clinically.

For our hepatobiliary and pancreatic surgeons, pancreatic cancer surgery is the most difficult. The surgery for the pancreatic head involves the removal and reconstruction of five organs. Even with the use of robots for surgery, mature surgeons require four to five hours, and complex cases can even take seven to eight hours.

Economic Observer?Are most of the patients you usually encounter with pancreatic cancer in advanced stage?

Li ZhaoYes, most visits are already unresectable with lymph node or distant metastasis.

Economic Observer: Is chemotherapy the main treatment plan given to them?

Li ZhaoMainly chemotherapy. Chemotherapy has also made progress in recent years, and through active chemotherapy, some patients can undergo surgical resection after their tumors shrink.

Economic Observer: How long can patients who can undergo surgery generally survive after surgery?

Li ZhaoThere are also 5 or 10 year survivors of early pancreatic cancer after surgery. Late stage unresectable cases can only be treated with chemotherapy, with a median survival of about 1 year.

Economic Observer?In the clinical trial of Revolution, the median survival time of the chemotherapy group was 6.7 months. Why is there such a big difference?

Li Zhao: The poor effect of the chemotherapy group may be related to the enrolled population, perhaps the patients with advanced pancreatic cancer. The strategy of this trial may be to select the most advanced patients to verify the efficacy.

Economic Observer?What is the biggest unsatisfied demand in the treatment of pancreatic cancer at present?

Li ZhaoFirstly, early screening, diagnosis, and treatment are very important. Many patients are diagnosed with pancreatic tumors that are already close to blood vessels and have lymphatic metastasis, which can result in poor treatment outcomes and may quickly recur after treatment.

Second, the biological mechanism of pancreatic cancer is not well understood at present. Pancreatic tumors have high interstitial hardness, similar to intrahepatic cholangiocarcinoma, making it difficult for drugs to enter the tumor, resulting in poor therapeutic effects. There have been previous studies using cell therapy combined with chemotherapy to attempt to break the interstitial barrier, but the effect has been limited. Now that targeted drugs have emerged, they may be able to overcome some of the barriers to drug delivery.

Economic Observer?There is no clear conclusion on the pathogenesis of pancreatic cancer.

Li ZhaoYes, no tumor has been completely conquered. The tumor is heterogeneous, also called pancreatic cancer, and the driving genes may be different.

Economic Observer??RAS mutation "is a word often heard by many pancreatic cancer patients and their families. Can you explain the role of RAS gene in normal cells and how to drive tumor after mutation?

Li ZhaoThe RAS gene is an important signaling molecule in cells, which opens and closes like a valve to control cell growth. After the mutation, the valve remains open and downstream signals continue to activate, leading to uncontrolled cell proliferation and the formation of tumors. Just like a traffic signal that remains green and vehicles continue to pass in all directions, it is easy to cause traffic congestion.

Economic Observer?Many families of patients on the Internet asked about the relationship between pancreatic cancer and pancreatitis, diabetes, and how to prevent high-risk groups.

Li ZhaoEarly screening, diagnosis, and treatment are key. Especially for patients with recurrent chronic pancreatitis, the transition from inflammation to cancer is a common feature of many tumors, such as hepatitis to liver cancer, gastritis to stomach cancer, and so on.

Other high-risk groups include those with a family history of pancreatic cancer, inherited pancreatic cancer susceptibility genes, obesity, and metabolic abnormalities. Long term high-fat diet and smoking are also closely related to pancreatic cancer.

In addition, diabetes is related to pancreatic cancer. pancreatic cancer may also lead to new diabetes if it destroys islet cells. I have encountered many patients in clinical practice who cannot understand why their blood sugar suddenly rises and need to check their blood sugar. I suggest also checking their pancreas, but I found that there is a tumor growing in the pancreas.

New drugs or changes in treatment patterns

Economic Observer: Compared with ten years ago, what changes have taken place in clinical attention and treatment plans for pancreatic cancer?

Li ZhaoFrom a surgical perspective, there have been improvements in surgical techniques (such as minimally invasive surgery and robotics), but the concept has not changed much, and radical resection is still the main approach. The real change lies in drugs, which did not actually undergo significant changes five years ago. The main changes have been the emergence of targeted drugs (such as RAS inhibitors) and immune drugs in the past two to three years. Overall, there haven't been many revolutionary changes.

Economic Observer?After RevoLution released phase III data on RAS pan inhibitors, many doctors were excited. Please evaluate the clinical significance of this drug in the history of pancreatic cancer treatment in the future. Does this result exceed your expectations?

Li ZhaoThe significance of this data is indeed quite significant. There have been many clinical studies in this area before, but few have significantly improved survival like this, which is a good result. At present, this company has disclosed approximate data and is expected to release detailed data at the American Society of Clinical Oncology (ASCO) annual meeting in May. If the detailed data is indeed good, it will be very heavyweight news.

Due to the improvement of previous chemotherapy regimens, it is difficult to achieve such significant benefits even if it is only extended by one or two months. It should be able to change the treatment pattern. Previously, when there were no drugs available, attempts could only be made within the scope of chemotherapy, immunization, etc. Now, with the addition of a drug targeting RAS targets, the treatment plan will change, such as combination therapy.

In addition, the current population targeted by Revolution is patients with unresectable pancreatic cancer. Can this medication be used for conversion therapy or neoadjuvant therapy for patients who are resectable or have resectable borders? There will be relevant studies in different clinical scenarios. After the release of new drugs, there are usually clinical studies targeting different populations and combination regimens. But it still depends on detailed data, such as subgroup analysis. It's a bit early to draw conclusions now.

Economic Observer?Many people may think that a drug can extend the overall survival period from 6 months to 13 months, which is only half a year. Why is the industry so excited?

Li Zhao: Many companies have worked hard in the field of pancreatic cancer for many years, and can make the survival period of patients with advanced pancreatic cancer exceed one year through medication (without surgery), which is a great progress from a scientific perspective. At present, clinically, the overall median survival period of all (early, middle and advanced) patients with pancreatic cancer is more than one year.

For patients, after an extension of six months, new drugs or therapies may emerge that can continue to benefit.

Economic Observer?When RAS universal inhibitor comes out, people will compare it with PD-1 (a revolutionary immunotherapy) and think that RAS inhibitor may become a pillar drug for the treatment of pancreatic cancer. What do you think?

Li ZhaoWe still need to look at clinical evidence. If the Phase III clinical study of Revolution is confirmed in a large sample (such as 1000 people), it will be high-level evidence-based medicine and will rewrite the guidelines. If it is only a small sample, it is necessary to accurately interpret the characteristics of the population in order to promote. Moreover, tumors have heterogeneity and may develop resistance or escape after medication, which should not be exaggerated.

Economic Observer?You mentioned combination therapy, and I saw that there are RAS inhibitors used in combination with immunotherapy, as well as those used in combination with chemotherapy. Which strategy do you think has the most promising prospects?

Li ZhaoFrom the overall treatment of pancreatic cancer, chemotherapy is still the cornerstone. It is too early to directly immunize or target pancreatic cancer, and chemotherapy is still the basis. So the first thing that may be tried is chemotherapy combined with RAS inhibitors. Because immunotherapy is not the gold standard in pancreatic cancer, only specific populations such as microsatellite instability can benefit, and most pancreatic cancer patients do not benefit from immunotherapy.