Case Report: Complete Remission of a Patient With Metastatic Gastric Cancer Treated With Nivolumab Combined With Chemotherapy After Palliative Surgery

Abstract

Metastatic advanced gastric cancer, for which treatment strategies are extremely limited, has a poor prognosis. Complete remission is rare. Patients usually lose the opportunity of therapeutic surgery because the lesions cannot be completely removed, although it can greatly prolong their survival time. Palliative surgery usually suggests bad outcomes. In recent years, the immune checkpoint inhibitor (ICI) nivolumab has shown significant efficacy in the treatment of advanced gastric cancer. However, its applicable conditions and optimal withdrawal time remain controversial owing to its low response rate and high incidence of immune-related adverse events. Herein, we introduce a 66-year-old male patient with advanced gastric cancer with multiple liver metastases who underwent laparoscopic total gastrectomy for acute gastric bleeding. The patient received eight cycles of S-1 plus oxaliplatin (SOX) and switched to eight cycles of SOX plus nivolumab combined regimen in a stable state, later achieving complete remission. There was no recurrence for 32 months after the surgery. This is the first reported case of gastric cancer with multiple liver metastases with long-term complete remission with nivolumab treatment after palliative surgery. The potential mechanism of complete remission was discussed through clinical, genomic, and immune characteristics. The patient had a history of psoriasis and was positive for programmed death ligand 1 (PD-L1), and the interaction of TP53 mutation and HER-2 (-) gene may be associated with complete remission.

Pathological complete response with nivolumab for recurrence of liver metastasis after gastrectomy of gastric cancer

“…With the new clinical development of immune checkpoint inhibitors, there have been some reports of nivolumab being used successfully in the perioperative period. We used PubMed to search for case reports in English with the key terms “Gastric Cancer”, “Stage IV”, “Nivolumab”, and “CR”, and summarized them in Table 1 [ 9 , 13 – 24 ]. The definition of CR in this search also included clinical and pathological CR.…”

A Case of Pathologically Complete Response After Nivolumab Combined with Chemotherapy in a Gastric Cancer Patient with Virchow’s Lymph Node Metastasis

“…13 However, with the progression of anticancer drug therapy, some case reports state that curative surgery for stage IV gastric cancer becomes possible after pre-operative treatment. [7][8][9][14][15][16] An international multicenter retrospective study verified the significance of conversion surgery and found that the median survival time of all resected patients who received pre-operative treatment for stage IV gastric cancer was 36.7 months. Those of R0, R1, and R2 resection were 56.6, 25.8, and 21.7 months, respectively.…”

“…31 Some case reports of conversion surgery use these agents. [7][8][9] However, the prognostic effect of pre-operative treatment using chemotherapy plus ICI for stage IV gastric cancer is still unclear, as with chemotherapy alone.…”

“…In previous reports, conversion surgery was performed based on the improvement in distant metastases on imaging studies. [7][8][9][14][15][16] Curative gastrectomy and adjuvant chemotherapy prolong the prognosis of patients with resected stage II and III gastric cancer compared to curative surgery alone [37][38][39][40] and have become standard treatments. In addition, in stage IV gastric cancer patients, adjuvant chemotherapy is weakly recommended in the Japanese gastric cancer treatment guidelines.…”

“…2,3 Recently, the efficacy in prolonging the prognosis for unresectable gastric cancer patients by immune checkpoint inhibitors (ICIs) have been demonstrated. [4][5][6] Although there have been some case reports of conversion surgery after pre-operative treatment, including ICIs, for stage IV gastric cancer, [7][8][9] there is no consensus regarding the optimal timing of curative gastrectomy. In this case, the indication for conversion surgery in a patient with stage IV gastric cancer was determined based on prior pathological diagnosis of unresectable factors.…”