Neoadjuvant Chemotherapy Strategies in Gastric Cancer Treatment

Neoadjuvant chemotherapy has become an integral component in the management of locally advanced gastric cancer, with the primary aims of tumour downstaging, improving R0 resection rates and eradicating micrometastatic disease prior to surgery. Traditional cytotoxic regimens—often combinations of fluoropyrimidines, platinum agents and taxanes—have demonstrated improvements in pathological response and survival compared with surgery alone. More recently, integration of targeted therapies and immunomodulatory agents into the neoadjuvant setting has opened new avenues for personalising treatment based on molecular biomarkers such as HER2 status, PD-L1 expression and microsatellite instability. Concurrent use of antiangiogenic drugs and immune checkpoint inhibitors alongside chemotherapy has shown promise in enhancing antitumour immunity and facilitating deeper pathological responses. Multimodal approaches including concurrent chemoradiotherapy are under investigation to further optimise local control. Across diverse geographic regions, strategies range from perioperative doublets or triplets to adaptive protocols guided by early biomarker response, reflecting a shift towards precision neoadjuvant therapy and multidisciplinary care.

Research from Nature Portfolio

Recent studies have explored the synergy between immune checkpoint blockade and cytotoxic chemotherapy in the neoadjuvant setting. In a phase 2 trial of atezolizumab followed by combination chemotherapy in resectable gastric and gastroesophageal junction cancers, sequential PD-L1 inhibition achieved major pathological response rates exceeding 70% and high rates of pathologic complete response, with translational analyses revealing early immune activation in responders. Another exploratory trial combined anti-PD-1 therapy, a VEGFR-2 inhibitor and standard fluoropyrimidine-based chemotherapy for cT4a/bN+ gastric cancer, reporting complete or major pathological responses in over 40% of patients and identifying potential biomarkers including microsatellite instability and tumour mutational burden. A further single-arm study assessed neoadjuvant camrelizumab with concurrent chemoradiotherapy, demonstrating a pathological complete response in one-third of participants and acceptable safety, thereby supporting further evaluation of immunoradiotherapy integrations.

Neoadjuvant Chemotherapy Strategies in Gastric Cancer Treatment publication trend

The graph below shows the total number of articles in neoadjuvant chemotherapy strategies in gastric cancer treatment across all publications each year (not limited to Nature Index journals).

Technical terms

Neoadjuvant chemotherapy: Systemic drug treatment administered before surgical resection to reduce tumour burden and eradicate micrometastases.

Pathological complete response (pCR): Absence of viable cancer cells in the surgical specimen following neoadjuvant therapy.

Major pathological response (MPR): Residual viable tumour cells ≤10% in the resected specimen after neoadjuvant treatment.

Immune checkpoint inhibitor (ICI): A drug that blocks inhibitory pathways in T cells, such as PD-1 or PD-L1, to enhance antitumour immunity.

Tumour microenvironment (TME): The complex milieu of immune cells, blood vessels, signalling molecules and extracellular matrix within and surrounding a tumour.

References

1. Effect of neoadjuvant chemotherapy in patients with gastric cancer: a PRISMA-compliant systematic review and meta-analysis. BMC Cancer (2018).
2. Neoadjuvant atezolizumab plus chemotherapy in gastric and gastroesophageal junction adenocarcinoma: the phase 2 PANDA trial. Nature Medicine (2024).
3. Neoadjuvant therapy with immune checkpoint blockade, antiangiogenesis, and chemotherapy for locally advanced gastric cancer. Nature Communications (2023).
4. The Neo-PLANET phase II trial of neoadjuvant camrelizumab plus concurrent chemoradiotherapy in locally advanced adenocarcinoma of stomach or gastroesophageal junction. Nature Communications (2022).
5. Neoadjuvant tislelizumab and tegafur/gimeracil/octeracil (S-1) plus oxaliplatin in patients with locally advanced gastric or gastroesophageal junction cancer: Early results of a phase 2, single-arm trial. Frontiers in Oncology (2022).
6. EORTC-1203-GITCG - the “INNOVATION”-trial: Effect of chemotherapy alone versus chemotherapy plus trastuzumab, versus chemotherapy plus trastuzumab plus pertuzumab, in the perioperative treatment of HER2 positive, gastric and gastroesophageal junction adenocarcinoma on pathologic response rate: a randomized phase II-intergroup trial of the EORTC-Gastrointestinal Tract Cancer Group, Korean Cancer Study Group and Dutch Upper GI-Cancer group. BMC Cancer (2019).