Phase III randomized, double-blind study of paclitaxel with and without Everolimus in patients with advanced gastric or esophagogastric junction carcinoma who have progressed after therapy with a fluoropyrimidine/platinum-containing regimen (RADPAC)
Mené sur 300 patients atteints d’un cancer de l’estomac ou d’un carcinome de la jonction œsogastrique de stade avancé (âge médian : 62 ans), cet essai de phase III évalue l’efficacité, du point de vue de la survie globale, et la toxicité de l’ajout de l’évérolimus au paclitaxel, après l’échec d’une thérapie à base de fluoropyrimidine ou de sels de platine
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 (10mg 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=0.3) or OS (everolimus, 6.1 vs. placebo, 5.0 months, HR 0.93, p=0.54). For patients with prior taxane use, everolimus improved PFS (everolimus, 2.7 vs. placebo 1.8 months, HR 0.69, p=0.03) and OS ( everolimus, 5.8 vs. placebo 3.9 months, HR 0.73, p=0.07). Combination of paclitaxel and everolimus was associated with significantly more grade 3?5 mucositis (13.3% vs. 0.7%; p<0.001). 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.