New drug combos make previously inoperable stomach cancer treatable

The recent application of targeted and immuno-oncology drugs to treat gastric cancer has significantly changed the outcome of inoperable gastric cancer.

In the past, conventional chemotherapy for gastric cancer consisted of only cytotoxic antitumor drugs. Recently, however, it has become possible to add targeted or immuno-oncology drugs to cytotoxic antitumor drugs, depending on the “biomarkers” of gastric cancer tissue.

“Recently, treatment for gastric cancer has improved. In the past, when there were no weapons, such as targeted and immuno-oncology drugs, the average life expectancy of conventional chemotherapy was about one year. However, it can be more than two to three years,” said Professor Kim Hyung-don of the Department of Oncology at Asan Medical Center on “KSMO TV.”

“Conventional chemotherapy” refers to chemotherapy based on the premise that a cure is difficult to achieve and is used for metastatic gastric cancer with distant metastases, gastric cancer that has recurred after surgery, and gastric cancer that has invaded organs such as the pancreas and peritoneum and cannot be surgically resected.

In all of these cases, chemotherapy is used to shrink the extent of the cancer to slow the progression of the tumor and increase survival.

“All gastric cancers are not the same one, and it will be important to apply the various weapons well,” Professor Kim said. “There are standard treatments that can be prescribed, but there are also many good treatments under clinical research. They are very promising. They're going to get better and better,” he said, predicting a shift in outcomes for inoperable gastric cancer.

Targeted or immuno-oncology drugs are applied by immunostaining a patient's gastric cancer tissue to identify biomarkers (biomarkers that can identify changes in the body using proteins, DNA, RNA, and metabolites). A representative biomarker of targeted antitumor drugs is HER2 (Human Epidermal Growth Factor 2), and immune antitumor drugs include PD-L1 (Programmed cell Death-Ligand 1) and MSI (Microsatellite Instability and Immunotherapy). The presence of these biomarkers in gastric cancer tissue can significantly change treatment outcomes by applying additional targeted or immuno-oncology drugs accordingly.

“The target is overexpressed in cancer cells but not in normal cells, so when targeting the target expressed in cancer, the anticancer effect can be increased while minimizing side effects,” Kim said, explaining the principle of targeted and immuno-oncology treatment.

The professor cited as an example a 67-year-old stomach cancer patient who had an extensive range of stomach cancer metastases, including lung metastases, lymph node metastases, and peritoneal metastases and was in such a bad condition that her stomach was full of water. However, her PD-L1 level was as high as 5 in biomarkers. She tested positive for MSI, so she was treated with immuno-oncology drugs in addition to cytotoxic antitumor drugs. She has been surviving for more than two years.

Professor Kim In-ho of the Department of Oncology at the Catholic University of Korea Seoul St. Mary's Hospital, who treated the patient, said, “The patient was very unwell and initially wanted to avoid chemotherapy. We took out ascites and did all the biomarker tests, and MSI-HIGH was positive. In this case, the patient may respond very well to immuno-oncology. I told her to be confident and not give up because she would improve with immuno-oncology. She started chemotherapy, and after one treatment, her ascites were almost gone.”

Patients who respond well to this type of chemotherapy can quickly improve their physical condition. People usually think that chemotherapy will make them feel worse, but the opposite is true.

“She couldn't eat well because she had ascites, but when the ascites were gone, she overate, and her condition improved too much,” Professor Kim said. “People think that chemotherapy will make them feel bad, but if they respond well, they feel very well. This patient has been on immuno-oncology for over two years and is doing well.”

When cytotoxic anticancer drugs are added to targeted or immuno-anti-cancer drugs to treat stomach cancer, some patients improve to the point where no cancer cells are left in the stomach.

“I had an inoperable patient with peritoneal metastases, and her biomarker HER2 was positive. After six to seven months of targeted anticancer therapy, the various lesions visible on CT, the stomach, and the peritoneum were not visible,” Professor Kim Hyung-don said. “I thought about surgery, but after the surgery, I checked the results with a pathology specimen, and there were no cancer cells left. The cancer cells were completely gone due to chemotherapy.”

He continued, “In the case of MSI-HIGH, we tried to operate at first, but it was locally advanced so that we couldn't resect it. We started treatment with a combination of immuno-oncology and cytotoxic anticancer drugs. The progress improved, so we tried to operate again. It was completely resected, and when we checked the pathology results, there were no cancer cells left.”

In recent years, inoperable gastric cancer has been increasingly moving into the realm of operable gastric cancer due to the therapeutic effectiveness of targeted and immuno-oncology drugs.

Professor Kim In-ho said, “We call it conversion surgery, but there are many cases where the anticancer drugs are much better than before, so even if there are metastases, they eventually undergo an operation.”