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. 2025 Aug 4;30(8):oyaf157.
doi: 10.1093/oncolo/oyaf157.

Efficacy of perioperative and neoadjuvant therapies in gastric and gastroesophageal junction adenocarcinoma: a network meta-analysis

Muhammad Umair Anjum  1 , Syed Arsalan Ahmed Naqvi  1 , Salman Ayub Jajja  1 , Ammad Raina  2 , Muhammad Umar Afzal  1 , Kunwer Sufyan Faisal  3 , Diana Segovia  1 , Zhaohui Jin  4 , Harry H Yoon  4 , Pedro Luiz Serrano Uson Junior  5 , Jason Starr  6 , Daniel H Ahn  1 , Tanios S Bekaii-Saab  1 , Irbaz Bin Riaz  1 , Mohamad Bassam Sonbol  1
Affiliations

Efficacy of perioperative and neoadjuvant therapies in gastric and gastroesophageal junction adenocarcinoma: a network meta-analysis

Muhammad Umair Anjum et al. Oncologist. .

Abstract

Background: Optimal treatment for resectable gastric and gastroesophageal junction (GEJ) adenocarcinoma remains unclear due to limited head-to-head comparisons among chemotherapy and chemoradiation regimens. This network meta-analysis aimed to determine the relative efficacy of available multimodality treatment regimens in these patients.

Methods: MEDLINE, EMBASE, Scopus, Web of Science, and CENTRAL were searched till September 20, 2024. Phase 3 randomized trials evaluating perioperative/neoadjuvant systemic therapy ± radiation in resectable gastric/GEJ adenocarcinoma were included. Primary outcomes were disease-free survival (DFS) and overall survival (OS). Frequentist network meta-analysis was conducted to compare hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: Fifteen trials (8072 patients) were analyzed. pFLOT (perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel) ranked highest for DFS in the overall population (P-score 91%), achieving significant improvements compared to surgery alone (HR 0.48, 95% CI, 0.38-0.60) and nCROSS (neoadjuvant paclitaxel, carboplatin, and radiotherapy) (0.67, 0.56-0.81). For OS, nPLF + nCRT(EP) (neoadjuvant cisplatin, leucovorin, and fluorouracil for induction, followed by etoposide, cisplatin, and radiotherapy) (P-score 90%) and pFLOT (P-score 87%) were the top regimens. pFLOT significantly outperformed surgery alone (0.57, 0.45-0.72) and nCROSS (0.73, 0.60-0.89). Based on the limited data available, adding neoadjuvant chemoradiation to pFLOT provided no additional OS (1.14, 0.76-1.72) or DFS (1.22, 0.83-1.82) benefit. Similarly, adding pembrolizumab to perioperative chemotherapy (cisplatin and fluorouracil/capecitabine) was not superior to pFLOT (DFS: 1.10, 0.71-1.69; OS: 1.09, 0.69-1.72).

Conclusions: pFLOT demonstrated superior efficacy in resectable gastric/GEJ adenocarcinoma, outperforming surgery alone, nCROSS, and alternative perioperative regimens. The additive role of immunotherapy requires further investigation to optimize patient selection and outcomes.

Keywords: disease-free survival; gastric cancer; gastroesophageal junction cancer; neoadjuvant; overall survival; perioperative.

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Conflict of interest statement

M.U.A., S.A.A.N., S.A.J., A.R., M.U.A., K.S.F., D.S., P.L.S.U.J., and I.B.R. do not have any relevant competing interests to disclose. Z.J. has served on the advisory board for Lilly, GlaxoSmithKline, Daiichi Sankyo/Astra Zeneca, Exelixis, and Elevar therapeutics (institution). H.Y. has received honoraria from Astellas, Elevation Oncology, MJH Life Sciences, and PRIME. He has also served in a consulting or advisory role for ALX Oncology, Amgen, AstraZeneca, BeiGene, Bristol Myer Squibb, Macrogenics, Merck, Novartis, OncXerna, and Zymeworks. Additionally, he has declared expert testimony for MJH Life Sciences and travel/accommodations/expenses from Astellas, BeiGene, Elevation Oncology, and PRIME. J.S. has served on the advisory board for Exelixis. He has also received research funding to his institution from Amgen, Camurus AB, Aminex Therapeutics, Cardiff, RayzeBio, Arcus Biosciences, and Perspective Therapeutics. D.H.A. has served as a consultant for Bayer, Exelixis, and Incyte. He also has stocks in Eli Lilly and Natera. T.S.B.-S. has received research funding to his institution from Agios, Arys, Arcus, Atreca, Boston Biomedical, Bayer, Eisai, Celgene, Lilly, Ipsen, Clovis, Seattle Genetics, Genentech, Novartis, Mirati, Merus, Abgenomics, Incyte, Pfizer, and BMS. He has also received consulting fees to his institution from Servier, Ipsen, Arcus, Pfizer, Seattle Genetics, Bayer, Genentech, Incyte, Eisai, Merus, Merck KGaA and Merck, and consulting fees to self from Stemline, AbbVie, Blueprint Medicines, Boehringer Ingelheim, Janssen, Daiichi Sankyo, Natera, TreosBio, Celularity, Caladrius Biosciences, Exact Science, Sobi, Beigene, Kanaph, Astra Zeneca, Deciphera, Zai Labs, Exelixis, Elevar, Illumina, Foundation Medicine and Sanofi, Glaxo SmithKline, and Xilio. Additionally, he has served on the independent data monitoring committee/data safety monitoring board for The Valley Hospital, Fibrogen, Suzhou Kintor, Astra Zeneca, Exelixis, Merck/Eisai, PanCan and 1Globe. He has also served on the scientific advisory board for Imugene, Immuneering, Xilis, Replimune, Artiva and Sun Biopharma, and received royalties from Uptodate. He has contributed to the following inventions/patents: (1) WO/2018/183488: HUMAN PD1 PEPTIDE VACCINES AND USES THEREOF – Licensed to Imugene; (2) WO/2019/055687: METHODS AND COMPOSITIONS FOR THE TREATMENT OF CANCER CACHEXIA – Licensed to Recursion. M.B.S. has received research funding to his institution from Taiho and Eli Lilly. He has also received consulting fees from Novartis (to self) and Boehringer Ingelheim Pharmaceuticals (to institution).

Figures

Figure 1.
Figure 1.
League table showing mixed treatment comparisons in the overall population for disease-free survival. The values in each cell represent the relative treatment effect (and 95% CI) of the treatment on the top, compared to the treatment on the left. Green color suggests relative treatment benefit. Light green suggests nonsignificant benefit and dark green suggests significant benefit. Red color suggests relative treatment harm. Light red suggests nonsignificant harm, and dark red suggests significant harm.
Figure 2.
Figure 2.
League table showing mixed treatment comparisons in the overall population for overall survival. The values in each cell represent the relative treatment effect (and 95% CI) of the treatment on the top, compared to the treatment on the left. Green color suggests relative treatment benefit. Light green suggests nonsignificant benefit and dark green suggests significant benefit. Red color suggests relative treatment harm. Light red suggests nonsignificant harm, and dark red suggests significant harm.
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