A case of locally advanced gastric cancer treated with nivolumab, trastuzumab, plus chemotherapy in a neoadjuvant setting

Gastric cancer is one of the most common and deadly cancers globally, but combination therapies are opening doors for patients with locally advanced disease—tumors that have spread to nearby tissues or lymph nodes but not distant organs—once thought too advanced for surgery. A 2006 study in the New England Journal of Medicine first highlighted how peri-operative chemotherapy (given before and after surgery) can shrink tumors and boost survival in resectable gastroesophageal cancer. Now, researchers are testing if adding immunotherapy to this mix can help even more patients become eligible for life-saving surgery.

In 2017, a 70-year-old Chinese man arrived at the National Cancer Center/Cancer Hospital in Beijing with persistent abdominal distension and weakness. Blood tests revealed moderate anemia (hemoglobin level 61 g/L)—a red flag for underlying disease. A gastroscopy and biopsy confirmed moderately to poorly differentiated adenocarcinoma, and immunohistochemistry (IHC) showed his tumor overexpressed HER2—a protein that fuels cancer growth. HER2 gene amplification (a sign of aggressive growth) was confirmed with fluorescence in situ hybridization (FISH).

A CT scan painted a concerning picture: a 67mm × 53mm tumor on the stomach’s lesser curvature, fused with the pancreas, and a swollen 24mm para-aortic lymph node (near the aorta, a major blood vessel). His cancer was staged T4bN3bM0—meaning the tumor had grown into the pancreas, spread to multiple nearby lymph nodes, and had no distant metastases. Critically, the tumor was initially unresectable—too advanced to remove with surgery.

A Personalized Neoadjuvant Regimen

The medical team, led by Dr. Yuan-Kai Shi (Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs), designed a tailored neoadjuvant (pre-surgery) regimen. Given the patient’s anemia, physical status, and HER2-positive tumor, they chose:

Chemotherapy: Reduced-dose oxaliplatin (150 mg IV on day 1) + S-1 (60 mg twice daily orally for 14 days). This combination is a standard first-line treatment for HER2-positive advanced gastric cancer in China, supported by studies in Lancet Oncology and Annals of Oncology.
Targeted therapy: Trastuzumab (initial 8 mg/kg IV dose, then 6 mg/kg every 3 weeks)—a drug that blocks HER2 and slows cancer growth.
Immunotherapy: Nivolumab (200 mg IV on day 8 every 3 weeks)—an anti-PD-1 drug that helps the immune system attack cancer. This addition was inspired by the ATTRACTION-2 trial (published in The Lancet), which showed nivolumab’s promise in Asian patients with advanced gastric cancer.

From Unresectable to Operable

After 2 cycles of treatment, the tumor shrank significantly—a “partial remission” by standard criteria. But the patient developed grade 2 thrombocytopenia (low platelet count), so the team adjusted chemotherapy for cycles 3–4: oxaliplatin + S-1 every 2 weeks (with lower S-1 doses) while continuing nivolumab and trastuzumab.

By the end of 4 cycles, the tumor had shrunk enough for surgery. In October 2017, surgeons performed a total gastrectomy (removal of the entire stomach) with D2 lymph node dissection (rigorous removal of nearby lymph nodes) and resected the para-aortic lymph node—once thought impossible. Pathologists found no cancer cells in the lymph nodes, and the residual tumor was classified as moderately differentiated adenocarcinoma (pathological stage ypT3N0).

Long-Term Success and Biomarker Insights

After surgery, the patient completed 4 more cycles of the regimen. For 16 months of follow-up, he remained free of cancer—a life-changing outcome for someone once deemed inoperable.

Biomarker testing added context to his response:

Tumor mutational burden (TMB): 11.1 mutations/Mb (medium)—a measure of genetic changes in the tumor.
Microsatellite status: Stable (MSI-S)—meaning the tumor’s DNA repair system was working normally.
Mismatch repair (MMR): Proficient (pMMR)—no defects in DNA repair.
PD-L1: Negative—no protein helping the tumor evade the immune system.

These findings are notable because immunotherapy typically works best in tumors with high TMB, MSI-high, or dMMR status. But this patient’s response suggests combining nivolumab with chemotherapy and trastuzumab may overcome these biomarkers—expanding hope for more patients.

Why This Case Matters

This case, reported by Shi-Yu Jiang, Yan Qin, and Yuan-Kai Shi of the Chinese Academy of Medical Sciences & Peking Union Medical College, is a breakthrough for locally advanced gastric cancer. It shows that neoadjuvant combination therapy (chemotherapy + targeted therapy + immunotherapy) can turn unresectable tumors into operable ones—and lead to long-term disease control. While nivolumab’s role in peri-operative care is still unproven, this patient’s success highlights the need for larger trials to validate the approach.

The patient provided written consent for the publication of his clinical information and images. The authors report no conflicts of interest.

References:

Cunningham D, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 2006;355:11–20.
Boku N, et al. Fluorouracil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer: a randomised phase 3 study. Lancet Oncol 2009;10:1063–1069.
Yamada Y, et al. Phase III study comparing oxaliplatin plus S-1 with cisplatin plus S-1 in chemotherapy-naïve patients with advanced gastric cancer. Ann Oncol 2015;26:141–148.
Kang YK, et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2017;390:2461–2471.

doi.org/10.1097/CM9.0000000000000241

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