P Schöffski1, P Reichardt2, J-Y Blay3, H Dumez4, J A Morgan5, I Ray-Coquard3, N Hollaender6, A Jappe6, G D Demetri5. 1. Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium. Electronic address: patrick.schoffski@uzleuven.be. 2. Department of Hematology and Oncology, HELIOS Klinikum Berlin-Buch, Berlin, Germany. 3. Department of Oncology, Centre Leon Berard, Lyon, France. 4. Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium. 5. Department of General Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. 6. Department of Oncology, Novartis Pharma AG, Basel, Switzerland.
Abstract
BACKGROUND: Imatinib is standard therapy for advanced gastrointestinal stromal tumors (GIST), but most patients develop resistance. This phase I-II study assessed the safety and efficacy of co-administering everolimus with imatinib in imatinib-resistant GIST. PATIENTS AND METHODS: In phase I, patients received imatinib (600/800 mg/day) combined with weekly (20 mg) or daily (2.5/5.0 mg) everolimus to determine the optimal dose. In phase II, patients were divided into two strata (progression on imatinib only; progression after imatinib and sunitinib/other tyrosine kinase inhibitor) and received everolimus 2.5 mg plus imatinib 600 mg/day. Primary end point was 4-month progression-free survival (PFS). RESULTS: Combination treatment was well tolerated. Common adverse events were diarrhea, nausea, fatigue, and anemia. In phase II strata 1 and 2, 4 of 23 (17%) and 13 of 35 (37%) assessable patients, respectively, were progression free at 4 months; median PFS was 1.9 and 3.5 months, and median overall survival was 14.9 and 10.7 months, respectively. In stratum 1, 36% had stable disease (SD) and 54% progressive disease (PD), while in stratum 2, 2% had partial response, 43% SD, and 32% PD. CONCLUSION: Predetermined efficacy criteria were met in both strata. The combination of everolimus and imatinib after failure on imatinib and sunitinib merits further investigation in GIST.
BACKGROUND:Imatinib is standard therapy for advanced gastrointestinal stromal tumors (GIST), but most patients develop resistance. This phase I-II study assessed the safety and efficacy of co-administering everolimus with imatinib in imatinib-resistant GIST. PATIENTS AND METHODS: In phase I, patients received imatinib (600/800 mg/day) combined with weekly (20 mg) or daily (2.5/5.0 mg) everolimus to determine the optimal dose. In phase II, patients were divided into two strata (progression on imatinib only; progression after imatinib and sunitinib/other tyrosine kinase inhibitor) and received everolimus 2.5 mg plus imatinib 600 mg/day. Primary end point was 4-month progression-free survival (PFS). RESULTS: Combination treatment was well tolerated. Common adverse events were diarrhea, nausea, fatigue, and anemia. In phase II strata 1 and 2, 4 of 23 (17%) and 13 of 35 (37%) assessable patients, respectively, were progression free at 4 months; median PFS was 1.9 and 3.5 months, and median overall survival was 14.9 and 10.7 months, respectively. In stratum 1, 36% had stable disease (SD) and 54% progressive disease (PD), while in stratum 2, 2% had partial response, 43% SD, and 32% PD. CONCLUSION: Predetermined efficacy criteria were met in both strata. The combination of everolimus and imatinib after failure on imatinib and sunitinib merits further investigation in GIST.
Authors: Swati Sikaria; Josefine Heim-Hall; Elizabeth H Diaz; Ronald Williams; Kamelesh Sankhala; Brenda Laabs; Monica Mita Journal: Target Oncol Date: 2013-02-21 Impact factor: 4.493
Authors: Shirish M Gadgeel; Danika L Lew; Timothy W Synold; Patricia LoRusso; Vincent Chung; Scott D Christensen; David C Smith; Laura Kingsbury; Antje Hoering; Razelle Kurzrock Journal: Cancer Chemother Pharmacol Date: 2013-09-22 Impact factor: 3.333