ABSTRACT
Background: There currently are no internationally recognised treatment guidelines for patients with advanced gastric cancer/gastro-oesophageal junction cancer (GC/GEJC) in whom two prior lines of therapy have failed. The randomised, phase III JAVELIN Gastric 300 trial compared avelumab versus physician's choice of chemotherapy as third-line therapy in patients with advanced GC/GEJC. Patients and methods: Patients with unresectable, recurrent, locally advanced, or metastatic GC/GEJC were recruited at 147 sites globally. All patients were randomised to receive either avelumab 10 mg/kg by intravenous infusion every 2 weeks or physician's choice of chemotherapy (paclitaxel 80 mg/m2 on days 1, 8, and 15 or irinotecan 150 mg/m2 on days 1 and 15, each of a 4-week treatment cycle); patients ineligible for chemotherapy received best supportive care. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety. Results: A total of 371 patients were randomised. The trial did not meet its primary end point of improving OS {median, 4.6 versus 5.0 months; hazard ratio (HR)=1.1 [95% confidence interval (CI) 0.9-1.4]; P = 0.81} or the secondary end points of PFS [median, 1.4 versus 2.7 months; HR=1.73 (95% CI 1.4-2.2); P > 0.99] or ORR (2.2% versus 4.3%) in the avelumab versus chemotherapy arms, respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 90 patients (48.9%) and 131 patients (74.0%) in the avelumab and chemotherapy arms, respectively. Grade ≥3 TRAEs occurred in 17 patients (9.2%) in the avelumab arm and in 56 patients (31.6%) in the chemotherapy arm. Conclusions: Treatment of patients with GC/GEJC with single-agent avelumab in the third-line setting did not result in an improvement in OS or PFS compared with chemotherapy. Avelumab showed a more manageable safety profile than chemotherapy. Trial registration: ClinicalTrials.gov: NCT02625623.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Choice Behavior , Esophageal Neoplasms/drug therapy , Esophagogastric Junction/pathology , Neoplasm Recurrence, Local/drug therapy , Practice Patterns, Physicians'/statistics & numerical data , Stomach Neoplasms/drug therapy , Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Adenocarcinoma, Mucinous/drug therapy , Adenocarcinoma, Mucinous/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal, Humanized , Carcinoma, Papillary/drug therapy , Carcinoma, Papillary/pathology , Carcinoma, Signet Ring Cell/drug therapy , Carcinoma, Signet Ring Cell/pathology , Decision Support Techniques , Esophageal Neoplasms/pathology , Female , Follow-Up Studies , Humans , International Agencies , Irinotecan/administration & dosage , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Paclitaxel/administration & dosage , Prognosis , Stomach Neoplasms/pathology , Survival Rate , Young AdultABSTRACT
The genetic structure of the human population in a random sample of 238 unrelated individuals from Garfagnana (Tuscany, Italy) was studied for five highly polymorphic serum proteins (GC, TF, PI, AHSG, ORM1) and three red cell isozymes (ACP, PGM1, ESD) by isoelectric focusing. Comparison with the gene frequencies from other districts of Tuscany has shown no significant deviation in seven out of eight polymorphic protein systems. Subtype allele frequencies of orosomucoid 1 (ORM1), which were not yet determined in Italian populations, are as follow: ORM1*F1 = 0.586, ORM1*F2 = 0.021, and ORM1*S = 0.393. The most striking features of this unique sample were the relatively high frequencies of PGM1*2B (0.093) and PI*I (0.013) alleles.
