Heikki Joensuu1, Mikael Eriksson2, Kirsten Sundby Hall2, Annette Reichardt2, Jörg T Hartmann2, Daniel Pink2, Giuliano Ramadori2, Peter Hohenberger2, Salah-Eddin Al-Batran2, Marcus Schlemmer2, Sebastian Bauer2, Eva Wardelmann2, Bengt Nilsson2, Harri Sihto2, Petri Bono2, Raija Kallio2, Jouni Junnila2, Thor Alvegård2, Peter Reichardt2. 1. Heikki Joensuu and Petri Bono, Comprehensive Cancer Center Helsinki; Heikki Joensuu, Harri Sihto, and Petri Bono, University of Helsinki, Helsinki; Raija Kallio, Oulu University Hospital, Oulu; Jouni Junnila, 4Pharma, Turku, Finland; Mikael Eriksson and Thor Alvegård, Lund University, Lund; Bengt Nilsson, Sahlgrenska University Hospital, Gothenburg, Sweden; Kirsten Sundby Hall, Oslo University Hospital, Oslo, Norway; Annette Reichardt, Daniel Pink, and Peter Reichardt, Sarkomzentrum Berlin-Brandenburg, HELIOS Klinikum Berlin-Buch, Berlin; Jörg T. Hartmann, Franziskus Hospital, Catholic Hospital Consortium Ostwestfalen, Bielefeld; Giuliano Ramadori, University of Göttingen, Göttingen; Peter Hohenberger, Mannheim University Medical Center, Mannheim; Salah-Eddin Al-Batran, Klinik für Onkologie und Hämatologie am Krankenhaus Nordwest, Frankfurt; Marcus Schlemmer, University Hospital Großhadern, Ludwig Maximilians University, Munich; Sebastian Bauer, Sarcoma Center, West German Cancer Center, Essen; and Eva Wardelmann, Gerhard-Domagk-Institute of Pathology, University Hospital Münster, Münster, Germany. heikki.joensuu@hus. 2. Heikki Joensuu and Petri Bono, Comprehensive Cancer Center Helsinki; Heikki Joensuu, Harri Sihto, and Petri Bono, University of Helsinki, Helsinki; Raija Kallio, Oulu University Hospital, Oulu; Jouni Junnila, 4Pharma, Turku, Finland; Mikael Eriksson and Thor Alvegård, Lund University, Lund; Bengt Nilsson, Sahlgrenska University Hospital, Gothenburg, Sweden; Kirsten Sundby Hall, Oslo University Hospital, Oslo, Norway; Annette Reichardt, Daniel Pink, and Peter Reichardt, Sarkomzentrum Berlin-Brandenburg, HELIOS Klinikum Berlin-Buch, Berlin; Jörg T. Hartmann, Franziskus Hospital, Catholic Hospital Consortium Ostwestfalen, Bielefeld; Giuliano Ramadori, University of Göttingen, Göttingen; Peter Hohenberger, Mannheim University Medical Center, Mannheim; Salah-Eddin Al-Batran, Klinik für Onkologie und Hämatologie am Krankenhaus Nordwest, Frankfurt; Marcus Schlemmer, University Hospital Großhadern, Ludwig Maximilians University, Munich; Sebastian Bauer, Sarcoma Center, West German Cancer Center, Essen; and Eva Wardelmann, Gerhard-Domagk-Institute of Pathology, University Hospital Münster, Münster, Germany.
Abstract
PURPOSE: Three years of adjuvant imatinib therapy are recommended for patients with GI stromal tumor (GIST) with high-risk features, according to survival findings in the Scandinavian Sarcoma Group XVIII/AIO (Arbeitsgemeinschaft Internistische Onkologie) trial. To investigate whether the survival benefits have persisted, we performed the second planned analysis of the trial. PATIENTS AND METHODS: Eligible patients had macroscopically completely excised, KIT-positive GIST with a high risk of recurrence, as determined by using the modified National Institutes of Health criteria. After surgery, the patients were randomly assigned to receive imatinib for either 1 or 3 years. The primary objective was recurrence-free survival (RFS), and the secondary objectives included survival. RESULTS: A total of 400 patients were entered onto this open-label study between February 4, 2004, and September 29, 2008. During a median follow-up of 90 months, 171 recurrences and 69 deaths were detected. Patients assigned to the 3-year group had longer RFS than those assigned to the 1- year group; 5-year RFS was 71.1% versus 52.3%, respectively (hazard ratio [HR], 0.60; 95% CI 0.44 to 0.81; P < .001), and survival was 91.9% versus 85.3% (HR, 0.60; 95% CI, 0.37 to 0.97; P = .036). Patients in the 3-year group survived longer in the subset with centrally confirmed GIST and without macroscopic metastases at study entry (93.4% v 86.8%; HR, 0.53; 95% CI, 0.30 to 0.93; P = .024). Similar numbers of cardiac events and second cancers were recorded in the groups. CONCLUSION: Three years of adjuvant imatinib therapy results in longer survival than 1 year of imatinib. High 5-year survival rates are achievable in patient populations with high-risk GIST.
RCT Entities:
PURPOSE: Three years of adjuvant imatinib therapy are recommended for patients with GI stromal tumor (GIST) with high-risk features, according to survival findings in the Scandinavian Sarcoma Group XVIII/AIO (Arbeitsgemeinschaft Internistische Onkologie) trial. To investigate whether the survival benefits have persisted, we performed the second planned analysis of the trial. PATIENTS AND METHODS: Eligible patients had macroscopically completely excised, KIT-positive GIST with a high risk of recurrence, as determined by using the modified National Institutes of Health criteria. After surgery, the patients were randomly assigned to receive imatinib for either 1 or 3 years. The primary objective was recurrence-free survival (RFS), and the secondary objectives included survival. RESULTS: A total of 400 patients were entered onto this open-label study between February 4, 2004, and September 29, 2008. During a median follow-up of 90 months, 171 recurrences and 69 deaths were detected. Patients assigned to the 3-year group had longer RFS than those assigned to the 1- year group; 5-year RFS was 71.1% versus 52.3%, respectively (hazard ratio [HR], 0.60; 95% CI 0.44 to 0.81; P < .001), and survival was 91.9% versus 85.3% (HR, 0.60; 95% CI, 0.37 to 0.97; P = .036). Patients in the 3-year group survived longer in the subset with centrally confirmed GIST and without macroscopic metastases at study entry (93.4% v 86.8%; HR, 0.53; 95% CI, 0.30 to 0.93; P = .024). Similar numbers of cardiac events and second cancers were recorded in the groups. CONCLUSION: Three years of adjuvant imatinib therapy results in longer survival than 1 year of imatinib. High 5-year survival rates are achievable in patient populations with high-risk GIST.
Authors: Heikki Joensuu; Mikael Eriksson; Kirsten Sundby Hall; Annette Reichardt; Barbara Hermes; Jochen Schütte; Silke Cameron; Peter Hohenberger; Philipp J Jost; Salah-Eddin Al-Batran; Lars H Lindner; Sebastian Bauer; Eva Wardelmann; Bengt Nilsson; Raija Kallio; Panu Jaakkola; Jouni Junnila; Thor Alvegård; Peter Reichardt Journal: JAMA Oncol Date: 2020-08-01 Impact factor: 31.777