Phase III Trial of Avelumab Maintenance After First-Line Induction Chemotherapy Versus Continuation of Chemotherapy in Patients With Gastric Cancers: Results From JAVELIN Gastric 100.

PURPOSE: The role of maintenance therapy for gastric (GC) or gastroesophageal junction cancer (GEJC) is unclear. We investigated avelumab (anti-programmed death ligand-1 [PD-L1]) maintenance after first-line induction chemotherapy for GC/GEJC. PATIENTS AND METHODS: JAVELIN Gastric 100 was a global, open-label, phase III trial. Eligible patients had untreated, unresectable, human epidermal growth factor receptor 2-negative, locally advanced or metastatic GC or GEJC. Patients without progressive disease after 12 weeks of first-line chemotherapy with oxaliplatin plus a fluoropyrimidine were randomly assigned 1:1 to avelumab 10 mg/kg every 2 weeks or continued chemotherapy, stratified by region (Asia v non-Asia). The primary end point was overall survival (OS) after induction chemotherapy in all randomly assigned patients or the PD-L1-positive randomly assigned population (≥ 1% of tumor cells; 73-10 assay). RESULTS: A total of 805 patients received induction; 499 were randomly assigned to avelumab (n = 249) or continued chemotherapy (n = 250). Median OS was 10.4 months (95% CI, 9.1 to 12.0 months) versus 10.9 months (95% CI, 9.6 to 12.4 months) and 24-month OS rate was 22.1% versus 15.5% with avelumab versus chemotherapy, respectively (hazard ratio [HR], 0.91; 95% CI, 0.74 to 1.11; P = .1779). In the PD-L1-positive population (n = 54), the HR for OS was 1.13 (95% CI, 0.57 to 2.23; P = .6352). In an exploratory analysis of the PD-L1-positive population, defined as combined positive score ≥ 1 (22C3 assay; n = 137), median OS was 14.9 months (95% CI, 8.7 to 17.3 months) with avelumab versus 11.6 months (95% CI, 8.4 to 12.6 months) with chemotherapy (unstratified HR, 0.72; 95% CI, 0.49 to 1.05). With avelumab and chemotherapy, treatment-related adverse events (TRAEs) occurred in 149 (61.3%) and 184 (77.3%) patients, including grade ≥ 3 TRAEs in 31 (12.8%) and 78 (32.8%) patients, respectively. CONCLUSION: JAVELIN Gastric 100 did not demonstrate superior OS with avelumab maintenance versus continued chemotherapy in patients with advanced GC or GEJC overall or in a prespecified PD-L1-positive population.

Maintenance avelumab versus continuation of first-line chemotherapy in gastric cancer: JAVELIN Gastric 100 study design.

Avelumab is a human anti-PD-L1 IgG1 monoclonal antibody that has shown antitumor activity in early phase studies in advanced/metastatic gastric/gastroesophageal junction cancer, including as first-line maintenance therapy. Here, we describe the design of JAVELIN Gastric 100 (NCT02625610), an open-label, Phase III trial. A total of 499 patients with locally advanced/metastatic HER2- gastric/gastroesophageal junction cancer adenocarcinoma, who had achieved at least stable disease following 12 weeks of first-line oxaliplatin/fluoropyrimidine chemotherapy, have been randomized 1:1 to receive avelumab maintenance therapy or continue chemotherapy. The primary objective is to demonstrate superior overall survival in all randomized patients or in the PD-L1+ population. Secondary objectives are to demonstrate superiority for progression-free survival and objective response rate, compare quality of life measures, and determine safety.

Severe periocular bleeding induced by bevacizumab in a patient with recurrent glioblastoma multiforme.

Bevacizumab is a humanized monoclonal antibody targeting vascular endothelial growth factor, and it has been shown to improve progression-free survival in patients with recurrent glioblastome multiforme when administered as second-line therapy. However, it has been associated with serious and fatal hemorrhagic events. Here, we present a 68-year-old male who developed severe periocular bleeding while on bevacizumab for recurrent temozolamide-resistant glioblastome multiforme.

Use of chemotherapy at the end of life in Turkey.

BACKGROUND: An increasing number of patients receive palliative chemotherapy near the end of life. The aim of this study is to evaluate the aggressiveness of chemotherapy in Turkish individuals near the end of life. METHODS: Patients diagnosed with solid tumors and died from 2010 to 2011 in the medical oncology department of Akdeniz University were included in the study. Data about the diagnosis, treatment details and imaging procedures were collected. RESULTS: Three hundred and seventy-three people with stage IV solid tumors died from 2010 to 2011 in our clinic. Eighty-nine patients (23.9%) patients underwent chemotherapy in the last month of life while 39 patients (10.5%) received chemotherapy in the last 14 days. The probability of undergoing chemotherapy in the last month of life was influenced by: age, 'newly diagnosed' patients, and performance status. There was no significant association of chemotherapy in the last month of life with gender and tumor type. Having a PET-CT scan did not alter the chemotherapy decision. CONCLUSION: In conclusion, chemotherapy used in the last month of life in a tertiary care center of Turkey is high. Increasing quality of life should be a priority near the end of life and physicians should consider ceasing chemotherapy and direct the patient to early palliative care.

Rising CEA levels in a patient with colon carcinoma: metachronous medullary thyroid cancer.

INTRODUCTION: Carcinoembryonic antigen (CEA) is a commonly used tumor marker, and its value in colon cancer is well established. However it is overexpressed in many different tumors. Here we report a case of colorectal cancer with high postoperative CEA levels that were associated with medullary thyroid carcinoma. CASE: A 60-year old man was operated for colon cancer. Postoperative CEA level was 107.6 ng/mL, while preoperative CEA level was unknown. For the detection of distant metastasis or local recurrence, we performed 18-flouro deoxyglycose (FDG) positron emission tomography (PET) and computed tomography (CT). We observed an increased FDG accumulation in the right lobe of the thyroid. The patient had cystic and non-metabolic lesions in the liver, and started a treatment with FOLFOX regimen. After 3 months of chemotherapy CEA was still as high as 146 ng/mL. There was no pathologic FDG uptake other than the thyroid nodule in PET-CT. Fine needle aspiration of the thyroid nodule revealed a follicular neoplasia. The patient underwent total thyroidectomy and histopathology revealed a medullary thyroid carcinoma. Postoperative CEA levels then lowered to normal ranges. CONCLUSION: The case we here report was a stage III colorectal cancer with high CEA levels. Our focus on searching a residual/metastatic disease made us blind to other possible explanations; in fact, none of us noticed the thyroid nodule. This case reminds us not to forget that high CEA levels can be associated with conditions other than colon cancer, such as thyroid medullary carcinoma.