There is a need for effective treatments in the second- or further line setting in advanced gastric cancer, especially for new agents. In the current trial we evaluated paclitaxel with RAD001 (everolimus) in patients with gastric carcinoma who have progressed after therapy with a fluoropyrimidine/platinum-containing regimen.
This is a randomized, double-blind, multi-center phase III study. Patients with gastric carcinoma or adenocarcinoma of the esophagogastric junction (EGJ) who have progressed after treatment with a fluoropyrimidine/platinum-containing regimen were randomly assigned to receive Paclitaxel (80 mg/m2) on day 1, 8 and 15 plus placebo (arm A) or RAD001 (10mg daily, arm B) d1-d28, repeated every 28 days as 2nd, 3rd or 4th line therapy. Primary end point was overall survival (OS), secondary endpoints were best overall response, disease control rate, progression free survival (PFS) and toxicity.
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 median PFS (placebo, 2.07 vs. RAD001, 2.2 months, HR 0.88, p = 0.3) or median OS (placebo, 5.0 vs. RAD001, 6.1 months, HR 0.93, p = 0.54). For patients with prior taxane use, RAD001 improved PFS (placebo 1.8 vs. RAD001, 2.7 months, HR 0.69, p = 0.03) and OS (placebo 3.9 vs. RAD001, 5.8 months, HR 0.73, p = 0.07). Combination of paclitaxel and RAD001 was tolerable, but the RAD001 arm was associated with significantly more grade 3-5 mucositis (13.3% vs. 0.7%; p
The addition of RAD001 to paclitaxel/RAD001 did not improve outcomes in pretreated metastatic gastric/EGJ cancer. Of note, activity was seen in the taxane pretreated group. Additional biomarker studies are planned to look for subgroups that may have a benefit.
Clinical trial identification
Protocol Code: CRAD001RDE35T clinicaltrials.gov NCT01248403
Legal entity responsible for the study
Krankenhaus Nordwest GmbH
S. Lorenzen: Advisory: Roche, BMS, Sanofi, Lilly. Honoraria: Merck, Lilly, Roche, Sanofi, BMS, Celgene; Research fund: Lilly. T. Goetze: Honoraria: MSD, Celgene. Consulting or advisory role: BMS, Baxalta-Shire. J. Riera Knorrenschild: Consulting/Advisory: Roche, Pierre Fabre Pharma. Travel: Mologen Berlin. P. Thuss-Patience: Consulting/Advisory Role: Roche, Lilly, BMS, MSD, Nordic, Pfizer. Research funding: Novartis. Travel, accomodations, expenses: Roche, Merck, Teva. A. Vogel: Honoraria: Novartis. K. Luley: Travel, accomodations, expenses: Ipsen, Novartis, Sanofi. D. Pink: Consulting or advisory role: Lilly, Clinigen. Research funding: PharmaMar. F. Kullmann: Honoraria: Roche. Consulting or advisory role: Celgene, Baxter, Lilly, Sanofi. Research Funding: Sanofi, Celgene. Travel, Accomodations, expenses: Celgene. H. Hebart: Stock or other ownership: Astellas, Gilead, Roche. Consulting or Advisory: Gilead, Roche. Travel: Roche, Celgene, BMS. J.T. Siveke: Consulting or Advisory Role: Merrimack, Baxalter, Celgene, Lilly. Research Funding: Celgene, BMS, 4SC, Novartis. Travel, accomodations, expenses: Roche, Celgene. N. Homann: Consulting or Advisory role: Sanofi, Roche, Amgen, Cellgene, Lilly. S-E. Al-Batran: Honoraria: Roche, Celgene, Lilly, Nordic Pharma. Consulting or advisory role: Merck, Roche, Celgene, Lilly, Nordic Pharma. Research funding: Merck, Roche, Celgene, Vifor, Medac, Hospira, Lilly. All other authors have declared no conflicts of interest.