The RADPAC trial evaluated paclitaxel with everolimus in patients with advanced gastroesophageal cancer (GEC) who have progressed after therapy with a fluoropyrimidine/platinum-containing regimen. Patients were randomly assigned to receive paclitaxel (80 mg/m2) on day 1, 8 and 15 plus everolimus (10 mg daily, arm B) d1-d28 or placebo (arm A), repeated every 28 days. Primary end point was overall survival (OS). Efficacy was assessed in the intention-to-treat population and safety in all patients who received at least one dose of treatment. This trial is registered with ClinicalTrials.gov, number NCT01248403. Between October 2011 and September 2015, 300 patients (median age: 62 years; median lines prior therapy: 2; 47.7% of patients had prior taxane therapy) were randomly assigned (arm A, 150, arm B, 150). In the intention to treat population, there was no significant difference in progression-free survival (PFS; everolimus, 2.2 vs placebo, 2.07 months, HR 0.88, P =.3) or OS (everolimus, 6.1 vs placebo, 5.0 months, HR 0.93, P =.54). For patients with prior taxane use, everolimus improved PFS (everolimus, 2.7 vs placebo 1.8 months, HR 0.69, P =.03) and OS (everolimus, 5.8 vs placebo 3.9 months, HR 0.73, P =.07). Combination of paclitaxel and everolimus was associated with significantly more grade 3-5 mucositis (13.3% vs 0.7%; P '.001). The addition of everolimus to paclitaxel did not improve outcomes in pretreated metastatic gastric/gastroesophageal junction (GEJ) cancer. Activity was seen in the taxane pretreated group. Additional biomarker studies are planned to look for subgroups that may have a benefit.