Confirmed complete response to nivolumab for advanced gastric cancer with peritoneal dissemination: a case report

Background Recent advances in cancer immunotherapy have been remarkable, with many reports on the clinical effects of immune checkpoint inhibitors. Nivolumab has been covered by the national health insurance in Japan as a third-line agent for advanced and recurrent gastric cancer since September 2017. The objective response rate for nivolumab for gastric cancer is 11.2%. However, patients’ quality of life during this treatment has not been examined. Here, we report a case in which multidisciplinary treatment, including with nivolumab, resulted in long-term survival and improved quality of life. Case presentation A 70-year-old Asian woman was referred for surgery for gastric cancer. Postoperative pathological examination revealed peritoneal dissemination, and the patient was diagnosed with stage IV gastric cancer. Therefore, she was treated with S-1 and cisplatin based on negative immunohistochemical staining of resected specimens for human epidermal growth factor receptor 2. However, owing to instability and adverse events, treatment was subsequently changed to S-1 monotherapy. Two years after changing to S-1 monotherapy, she developed recurrence of peritoneal dissemination and was treated with docetaxel. Radiation therapy was also used because the recurrent lesions were local. However, 6 months later, new peritoneal dissemination and lymph node metastasis were observed and nivolumab was started. Subsequent abdominal computed tomography revealed a marked reduction in the disseminated nodules and lymphadenopathy. After 54 cycles of nivolumab, the lesions had disappeared completely. The patient has not developed side effects, including immune-responsive adverse events, has improved quality of life, and is returning to work. She is currently taking nivolumab, and there is no evidence of recurrence approximately 3 years after starting nivolumab. Conclusions Nivolumab may have beneficial effects in some patients with advanced or recurrent gastric cancer. Although the prognosis for gastric cancer and peritoneal dissemination is poor, multidisciplinary treatment that includes nivolumab may lead to long-term survival.

Drug-induced thrombocytopenia associated with trastuzumab in a patient with HER2-positive recurrent gastric cancer

Here, we report a 57-year-old female patient with HER2-positive recurrent gastric cancer who experienced drug-induced thrombocytopenia associated with trastuzumab, a humanized anti-HER2 monoclonal antibody. Shortly after the initiation of S-1, oxaliplatin, and trastuzumab chemotherapy, the patient experienced severe thrombocytopenia and did not respond to platelet transfusions. Based on the findings of increased numbers of polynuclear megakaryocytes in the bone marrow and an elevated level of platelet-associated IgG (PA-IgG), the patient was diagnosed with drug-induced thrombocytopenia (DITP). The platelet count recovered rapidly with oral prednisolone (1 mg/kg). Since we initially suspected oxaliplatin as the causal agent, S-1 was restarted as a monotherapy, followed by trastuzumab after a 3-week interval, without oxaliplatin. On the second day after the addition of trastuzumab, severe thrombocytopenia occurred again, which suggests that trastuzumab was responsible for the DITP. The patient no longer experienced severe thrombocytopenia during the subsequent S-1 and oxaliplatin chemotherapy, which supports this hypothesis.

Lymphocyte-to-Monocyte Ratio Is a Predictive Biomarker of Response to Treatment with Nivolumab for Gastric Cancer

<b><i>Introduction:</i></b> Patients with unresectable or recurrent gastric cancer who have an objective response (OR) to nivolumab monotherapy are expected to have a good long-term prognosis. However, the OR rate for nivolumab treatment is low at 11%, and there is a need for biomarkers to predict the treatment response. This study aimed to analyze the significance of systemic inflammation-related variables and clinicopathologic characteristics as predictive markers of response to nivolumab monotherapy in patients with advanced gastric cancer. <b><i>Methods:</i></b> In this retrospective cohort study, we enrolled 71 consecutive patients who received nivolumab monotherapy for unresectable or recurrent gastric cancer. Receiver operating characteristic curve analysis was performed to determine the cutoff values of systemic inflammation-related variables, predictors of treatment response, and other prognostic factors related to nivolumab therapy. We focused on systemic inflammation-related variables measured before nivolumab induction and 2 weeks after its first administration and performed multivariate analysis to assess whether they could be used as prognostic factors. <b><i>Results:</i></b> Multivariate analysis revealed that a lymphocyte-to-monocyte ratio (LMR) of ≤3.28 after 2 weeks of initial nivolumab treatment (2wLMR) is a statistically significant predictor of treatment response (<i>p</i> = 0.012). The progression-free survival (PFS) rate of patients with liver metastasis was significantly worse than that of the other patients (1-year PFS: 0.0 vs. 24.4%, respectively; <i>p</i> = 0.005). The overall survival (OS) of patients with a low 2wLMR was significantly longer than that in patients with a high 2wLMR (1-year OS: 37.4 vs. 18.9%, respectively; <i>p</i> = 0.022). <b><i>Conclusions:</i></b> Thus, the 2wLMR could be a useful biomarker to predict response to nivolumab treatment and the prognosis of unresectable and recurrent gastric cancer.