A research team at Severance Hospital found that exposure to antibiotics in patients with advanced gastric cancer diminishes the effectiveness of immunotherapy treatments.
The incidence of gastric cancer is particularly high in Asia. In Korea, it was the fourth most common cancer in 2020, according to the National Cancer Registry statistics, with a 10.8 percent incidence rate, making it one of the cancers with a high mortality rate, alongside lung, liver, and colorectal cancer.
Especially the prognosis of advanced gastric cancer that is not detected early or recurrent gastric cancer is very poor, with a five-year survival rate of around 10 percent.
Recently, with the development of immunotherapies such as Opdivo and Keytruda, the options for treating gastric cancer and the overall survival rates for patients have increased.
However, the lack of research on indicators that can predict the response to immunotherapy limits the provision of appropriate treatment based on patient characteristics.
The study was conducted by a team, led by comprising Professors Jung Min-kyu and Kim Chang-gon from Yonsei Cancer Center, Jeong Hee-cheol from Gangnam Severance Hospital, Shin Su-jin from Yonsei University College of Medicine, Lee Jeong-seok and Koh June-young from KAIST, and Nam Young-do and Shin Ji-hee from the Korea Food Research Institute.
The team revealed that exposure to antibiotics before immunotherapy in advanced gastric cancer patients leads to a decrease in progression-free survival rate and overall survival rate.
The team concluded so after analyzing treatment outcomes for 253 patients with advanced gastric cancer who received immunotherapy at Yonsei Cancer Center and Gangnam Severance Hospital from Jan. 2014 to July 2021, to identify factors that could predict treatment response.
The analysis showed that patients exposed to antibiotics within 28 days before receiving immunotherapy experienced a 65 percent and 55 percent decrease in progression-free and overall survival rates, respectively, compared to those who were not exposed to antibiotics.
In contrast, in patients treated with cytotoxic chemotherapy, exposure to antibiotics within 28 days before treatment did not show a significant correlation with treatment outcomes.
The research team also analyzed blood and fecal samples from the patients.
The results indicated that patients exposed to antibiotics before immunotherapy showed a decrease in gut microbiota diversity and a decline in the function of T cells fighting against cancer cells.
The team stressed that this confirmed that the diversity of the gut microbiota and the level of decline in circulating T cell function could be indicators for predicting the effectiveness and survival of immunotherapy treatment.
"This study confirmed that pre-treatment exposure to antibiotics in gastric cancer patients negatively impacts the outcomes of immunotherapy treatment,” Professor Jung said. “We expect that this will enable us to provide more advanced treatment methods tailored to individual patient characteristics in the future."
The results of the research were published in Cell Reports Medicine.