Different Cycles of Neoadjuvant PD-1 Blockades + Chemotherapy for Advanced Gastric Cancer

Official title

The Comparison of Different Cycles of PD-1 Blockades Combined with Chemotherapy As Neoadjuvant Therapy for Patients with Advanced Gastric Cancer

Overview

The goal of this observational study is to analyze the impact of different durations of neoadjuvant PD-1 inhibitor combined with chemotherapy on tumor regression and safety in patients with advanced gastric cancer. The main questions it aims to answer are: * Does the duration of neoadjuvant treatment influence tumor regression grading (TRG)? * How does treatment duration affect perioperative safety and clinical outcomes? Participants who have previously undergone neoadjuvant PD-1 inhibitor combined with chemotherapy followed by surgery as part of their routine medical care will have their clinical data retrospectively reviewed and analyzed.

Interventions

• Drug ≤4 cycles of neoadjuvant PD-1 Inhibitors combined with chemotherapy
  Any PD-1 inhibitors combined with any chemotherapy regimen given before surgery for no more than 4 cycles
• Drug ≥5 cycles of neoadjuvant PD-1 Inhibitors combined with chemotherapy
  Any PD-1 inhibitors combined with any chemotherapy regimen given before surgery for no less than 5 cycles
• Procedure Gastrectomy
  Any type of surgical procedure for gastric adenocarcinoma patients in which part or all of the stomach is removed

Primary outcome measures

• Tumor Regression Grading (TRG) [Time frame: Approximately 1 week after surgery (when the pathology examination report available)]

Secondary outcome measures (8)

• Safety [Time frame: From the start of neoadjuvant chemotherapy to 7 days after surgery]
• R0 resection [Time frame: Approximately 1 week after surgery (when the pathology examination report available)]
• Operative time [Time frame: On the day of the surgery (can be obtained immediately after the completion of the surgery)]
• Time to first flatus [Time frame: From date of surgery until the date of first flatus, assessed up to 10 days post-surgery]
• Nutritional Risk Screening 2002 (NRS 2002) [Time frame: Approximately 1 week after completing all neoadjuvant therapy]
• YpTNM staging [Time frame: Approximately 1 week after surgery (when the pathology examination report available)]
• Dissected lymph node number [Time frame: Approximately 1 week after surgery (when the pathology examination report available)]
• Positive lymph node number [Time frame: Approximately 1 week after surgery (when the pathology examination report available)]

Eligibility criteria

Inclusion criteria

• Non-bedridden patients aged 18-90 years;
• Histologically confirmed gastric or gastroesophageal junction adenocarcinoma by biopsy;
• Evaluated as resectable advanced gastric cancer via CT, MRI, or laparoscopic exploration;
• No prior anti-tumor treatments such as chemotherapy, radiotherapy, or immunotherapy;
• No history of other malignancies within the past 5 years;
• Received at least one cycle of PD-1 inhibitor combined with chemotherapy preoperatively, with no restrictions on the specific PD-1 inhibitor or chemotherapeutic agents;
• Underwent radical gastrectomy after neoadjuvant therapy;
• No severe underlying diseases.

Exclusion criteria

• Incomplete or inaccessible clinical and pathological data;
• Postoperative pathology confirming non-gastric or non-gastroesophageal junction adenocarcinoma;
• Distant metastases present prior to treatment;
• Concurrent diagnosis of other malignancies.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

China · 1 center

• Chinese PLA General Hospital — Beijing

Publications

• Hayashi T, Yoshikawa T, Sakamaki K, Nishikawa K, Fujitani K, Tanabe K, Misawa K, Matsui T, Miki A, Nemoto H, Fukunaga T, Kimura Y, Hihara J. Primary results of a randomized two-by-two factorial phase II trial comparing neoadjuvant chemotherapy with two and four courses of cisplatin/S-1 and docetaxel/cisplatin/S-1 as neoadjuvant chemotherapy for advanced gastric cancer. Ann Gastroenterol Surg. 2020 PMID 33005849
• Yoshikawa T, Tanabe K, Nishikawa K, Ito Y, Matsui T, Kimura Y, Hirabayashi N, Mikata S, Iwahashi M, Fukushima R, Takiguchi N, Miyashiro I, Morita S, Miyashita Y, Tsuburaya A, Sakamoto J. Induction of a pathological complete response by four courses of neoadjuvant chemotherapy for gastric cancer: early results of the randomized phase II COMPASS trial. Ann Surg Oncol. 2014 Jan;21(1):213-9. doi: 10.1 PMID 23838904
• Lorenzen S, Gotze TO, Thuss-Patience P, Biebl M, Homann N, Schenk M, Lindig U, Heuer V, Kretzschmar A, Goekkurt E, Haag GM, Riera-Knorrenschild J, Bolling C, Hofheinz RD, Zhan T, Angermeier S, Ettrich TJ, Siebenhuener AR, Elshafei M, Bechstein WO, Gaiser T, Loose M, Sookthai D, Kopp C, Pauligk C, Al-Batran SE; AIO and SAKK Study Working Groups. Perioperative Atezolizumab Plus Fluorouracil, Leucovo PMID 37963317
• Sun W, Veeramachaneni N, Al-Rajabi R, Madan R, Kasi A, Al-Kasspooles M, Baranda J, Saeed A, Phadnis MA, Godwin AK, Olyaee M, Streeter N, Nagji A, Dai J, Williamson S. A phase II study of perioperative pembrolizumab plus mFOLFOX in patients with potentially resectable esophagus, gastroesophageal junction (GEJ), and stomach adenocarcinoma. Cancer Med. 2023 Aug;12(15):16098-16107. doi: 10.1002/cam4.6 PMID 37326317
• Yuan SQ, Nie RC, Jin Y, Liang CC, Li YF, Jian R, Sun XW, Chen YB, Guan WL, Wang ZX, Qiu HB, Wang W, Chen S, Zhang DS, Ling YH, Xi SY, Cai MY, Huang CY, Yang QX, Liu ZM, Guan YX, Chen YM, Li JB, Tang XW, Peng JS, Zhou ZW, Xu RH, Wang F. Perioperative toripalimab and chemotherapy in locally advanced gastric or gastro-esophageal junction cancer: a randomized phase 2 trial. Nat Med. 2024 Feb;30(2):552 PMID 38167937
• Raimondi A, Lonardi S, Murgioni S, Cardellino GG, Tamberi S, Strippoli A, Palermo F, De Manzoni G, Bencivenga M, Bittoni A, Chiodoni C, Lorenzini D, Todoerti K, Manca P, Sangaletti S, Prisciandaro M, Randon G, Nichetti F, Bergamo F, Brich S, Belfiore A, Bertolotti A, Stetco D, Guidi A, Torelli T, Vingiani A, Joshi RP, Khoshdeli M, Beaubier N, Stumpe MC, Nappo F, Leone AG, Pircher CC, Leoncini G, S PMID 39637944
• Andre T, Tougeron D, Piessen G, de la Fouchardiere C, Louvet C, Adenis A, Jary M, Tournigand C, Aparicio T, Desrame J, Lievre A, Garcia-Larnicol ML, Pudlarz T, Cohen R, Memmi S, Vernerey D, Henriques J, Lefevre JH, Svrcek M. Neoadjuvant Nivolumab Plus Ipilimumab and Adjuvant Nivolumab in Localized Deficient Mismatch Repair/Microsatellite Instability-High Gastric or Esophagogastric Junction Adenoca PMID 35969830
• Rha SY, Oh DY, Yanez P, Bai Y, Ryu MH, Lee J, Rivera F, Alves GV, Garrido M, Shiu KK, Fernandez MG, Li J, Lowery MA, Cil T, Cruz FM, Qin S, Luo S, Pan H, Wainberg ZA, Yin L, Bordia S, Bhagia P, Wyrwicz LS; KEYNOTE-859 investigators. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phas PMID 37875143

Identifiers

NCT: NCT06798376 · S2024-823

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗