Editor's note: With the continuous advancement of medical technology, the field of gastric cancer treatment has ushered in new breakthroughs. On June 11, 2024, the 14th CGOG Congress was successfully opened, and many gastrointestinal oncology experts and scholars gathered through an online platform to discuss the latest progress in gastric cancer treatment. In the first session of the conference, ASCO Express for Gastric Cancer, Professor Deng Ting from Tianjin Medical University Cancer Hospital gave us a wonderful speech on the progress of the perioperative treatment of gastric cancer in ASCO in 2024. Professor Deng systematically elaborated on the immunology, chemotherapy and multi-dimensional research of perioperative treatment of gastric cancer, especially the application and progress of immunotherapy in this field, providing new academic perspectives and clinical guidance for the participants.
Expert presentation
Deng Ting
Director of the Department of Digestive Oncology, Tianjin Medical University Cancer Hospital, Deputy Chief Physician, Master Supervisor
Member of the Standing Committee of the Tumor Supportive Care Committee of the Chinese Anti-Cancer Association
Member of the Standing Committee of the CMUP Special Committee of the Chinese Anti-Cancer Association
Member of the Chemotherapy Committee/Gastric Cancer Committee of the Chinese Anti-Cancer Association
Member of the Clinical Research Committee of Oncology Drugs of the Chinese Anti-Cancer Association
Member of the Standing Committee of the Gastrointestinal Oncology Committee of the Chinese Geriatric Health Care Association
Member of the Standing Committee of the Oncology Committee of the Chinese Association of Research Hospitals
Vice Chairman of the Colorectal Cancer Committee of the Beijing Cancer Prevention and Control Society
Member of the Standing Committee of the CSCO Youth Expert Committee
Chairman of the Tumor Nutrition and Supportive Treatment Committee of Tianjin Anti-Cancer Association
He is the chairman-elect of the Tumor Drug Clinical Research Committee of Tianjin Anti-Cancer Association
Abstract No. 4000 EA2174 Research
The study focused on patients with locoregional E/GEJ adenocarcinoma to explore the effect of neoadjuvant therapy on pathologic complete response rate (pCR). The study is mainly divided into two phases, the first phase explores the preoperative neoadjuvant treatment mode, and the patients will be divided into two groups: group A concurrent chemoradiotherapy (paclitaxel + carboplatin + radiotherapy), and group B concurrent chemoradiotherapy combined with nivolumab. The second phase is to explore the postoperative adjuvant treatment modality, nivolumab alone or in combination with ipilimumab.
The data presented this time is the first phase of the study, and the trial included a total of 275 patients, of which 89.5% were male, more than 90% were white patients, and 60% were patients with esophageal adenocarcinoma, so the results of the study may be more applicable to the European and American population. By the end of the first phase, the discharge rate was 42.5% in the chemoradiotherapy group and 50.7% in the experimental group, and the reasons for dropout included disease progression or recurrence (about 20%) and patient rejection (20-30%).
From the perspective of the primary endpoint of the first stage, the pCR rate of chemoradiotherapy combined with nivolumab did not significantly improve the pCR rate, which was 21% and 24.8% in the two groups, respectively, which is inconsistent with the results of previous small sample size studies, and the optimal timing and combination strategy of immunotherapy combined with chemoradiotherapy need to be further explored. Future studies will explore the sequence of immunotherapy before and after chemoradiotherapy, and how to screen dominant populations to improve treatment efficacy.
摘要号4073 KEYOTE-585研究
The KEYOTE-585 Phase III study investigated the efficacy of pembrolizumab (pembro) or placebo (pbo) in combination with chemotherapy (chemo) as a perioperative treatment for locally advanced, resectable gastric cancer or gastroesophageal junction cancer (G/GEJ). Its EFS (event-free survival) results were reported at the ESMO meeting last year, and although statistical differences were not reached, the results of the study were not clinically negative.
Previous data were used for post-hoc analyses of pCR (pathologic complete response) and MPR (major pathologic response). The results of the study showed that the pembrolizumab + chemotherapy group increased the pCR rate by about 11%, the MPR rate increased by less than 10%, and the tumor downstage and lymph node downstage were both about 11%, indicating that the patient group that may benefit is about 10%.
Further analysis showed that the proportion of lymph node downstage and T stage downstage in patients receiving combination chemotherapy appeared to remain around 10% to some extent. This suggests that patients who achieve pCR or MPR are more effective than patients who do not meet these criteria for response, both in terms of EFS (event-free survival) and OS (overall survival). In particular, patients who achieved MPR were treated with pembrolizumab and had an improvement in efficacy of about 10%. However, among patients who did not achieve MPR, there was no statistically significant difference between the two groups, and survival curves were generally the same. In terms of OS, immunotherapy does not appear to provide the expected additional benefits to the 10% of beneficiaries even when pcR or MPR status is achieved.
Finally, from the perspective of N0 (no lymph node metastasis) and downstaging, there was no significant difference between chemotherapy plus pembrolizumab in patients who reached N0 and downstaged. Conversely, in the patient population that did not achieve de-prostaging, chemotherapy plus pembrolizumab did improve efficacy, with an approximately 10% increase. We look forward to further interpretation and analysis of these results in future studies.
A phase II clinical study of toripalimab in combination with neoadjuvant chemotherapy without cycle interval chemotherapy in locally advanced G/GEJ cancer
The study conducted a clinical study for Henan Provincial Cancer Hospital to evaluate the effect of extending the interval between chemotherapy cycles and thereby reducing the dose intensity of chemotherapy drugs on clinical efficacy. The study compared two different interval FLOT regimens in combination with toripalimab: a two-week regimen (Q2W×4 cycles) and a three-week regimen (Q3W×3 cycles). The study included 69 patients with an overall PCR rate of 26.1% and an MPR rate of 55.1%. There was no statistically significant difference in pCR rate and MPR rate between the two- and three-week treatment groups. In the three-week treatment group, patients with PD-L1 CPS≥1 had a higher pCR rate of 42.1%. Analysis of peripheral blood lymphocyte subsets showed that the proportion of T lymphocytes increased significantly before and after treatment in the three-week treatment group. In the two-week treatment group, the proportion of T lymphocytes decreased. Prolonged treatment cycles may reduce the impact of chemotherapy on lymphocytes and may improve the efficacy of immunotherapy. Due to the small sample size, these preliminary results require further large-scale studies to validate.
Other small sample studies
summary
EA2174 study: CCRT+Nivo did not improve the PCR rate, and how to arrange the combined immunization model needs to be reconsidered.
KEYOTE-585 study: Longer survival benefit above MRP, immunotherapy improved EFS in this subset of patients, but the proportion of patients was lower (about 10%), and subsequent complications led to little benefit in OS.
Other small studies, including tislelizumab plus chemotherapy and nivolimum plus SOX, have limited sample sizes but provide preliminary evidence that the combination of perioperative chemotherapy and immunotherapy may lead to longer survival.
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