Benefit of Chemoradiotherapy Versus Chemotherapy After Induction Therapy for Conversion of Unresectable Into Resectable Pancreatic Cancer: The Randomized CONKO-007 Trial
Abstract
PURPOSE To determine the benefit, measured as complete removal of a tumor so that no tumor cells are detectable during histopathologic examination of the resection margin (R0 resection rate), of induction chemotherapy plus chemoradiotherapy (CRT) compared with chemotherapy alone for unresectable pancreatic tumors. PATIENTS AND METHODS CONKO-007, an investigator-initiated open-label, multicentric, phase III randomized clinical trial, enrolled 525 patients with unresectable tumors, and 495 patients received induction chemotherapy (402 with fluorouracil, irinotecan, and oxaliplatin [FOLFIRINOX] and 93 with gemcitabine). Patients without progression after 3 months of induction chemotherapy (n = 336) were randomly assigned for continuation of the same chemotherapy (n = 167) or CRT (n = 169; 50.4Gy concurrently with gemcitabine). Resectability was centrally reassessed by a panel of surgeons. Surgery was recommended if possible. After an interim analysis, the primary end point was changed from overall survival (OS) to overall R0 resection rate because of slow recruitment. The median follow-up was 76 months. Important planned secondary end points were R0 resection rate in the surgically treated population and OS. RESULTS The primary end point (overall R0 resection rate) was not significantly different between treatment arms with 25% (43 of 169) in the CRT arm versus 18% in the chemotherapy arm (30 of 167; P = .113). Secondary end point analysis showed that surgery was performed equally often ( P = .91); R0 resection rate in patients who underwent surgery was higher after CRT, 69.4% (43 of 62) compared with chemotherapy alone: 50.0% (30 of 60 patients, P = .04). Other parameters of resection (ratio of R0/R1/R2/no resection) also favored CRT ( P = .02). No difference in OS was seen between treatment arms (hazard ratio [HR], 0.937 [95% CI, 0.747 to 1.174]; P = .57; randomly assigned intention-to-treat patients). Surgery was associated with longer OS ( P < .001, HR, 0.525 [95% CI, 0.408 to 0.676]). CONCLUSION Although not improving overall R0 resection rate or survival, CRT enables a R0 resection in surgically treated patients more often than chemotherapy alone.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (23)
Rainer Fietkau
Michael Ghadimi
From Bielefeld University, Medical School and University Medical Center Ostwestfalen-Lippe, Campus Hospital Lippe, Detmold, Germany (J.H.); the Department of Radiation Oncology, Medical University of Graz, Graz, Austria (T.B.); the Clinical Trials Unit, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany (C.S.); the Institute of Surgical Pathology, University Medical Center Freiburg, Germany (P.B.); the Department of Surgery, University Medical Center Schleswig-Holstein–Campus Lübeck, Lübeck, Germany (B.K., T.K.); Comprehensive Cancer Center Augsburg, Faculty of Medicine, University of Augsburg, Augsburg, Germany (R.C.); the Department of General and Visceral Surgery, University Medical Center Freiburg, Freiburg, Germany (S.U.); the Department of General, Visceral, and Thoracic Surgery, University Medical Center Hamburg–Eppendorf, Hamburg, Germany (J.R.I.); the Department of Gastrointestinal Surgery, IRCCS San Raffaele Scientific Institute and San Raffaele Vita-Salute Universi...
Robert Grützmann
Uwe A. Wittel
Lutz Jacobasch
11Praxis of Haematology and Oncology, Dresden, Germany
Waldemar Uhl
Department of General and Visceral Surgery, St. Josef Hospital, Ruhr University, Bochum, Germany
Roland S. Croner
Wolf Otto Bechstein
Ulf Peter Neumann
From Bielefeld University, Medical School and University Medical Center Ostwestfalen-Lippe, Campus Hospital Lippe, Detmold, Germany (J.H.); the Department of Radiation Oncology, Medical University of Graz, Graz, Austria (T.B.); the Clinical Trials Unit, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany (C.S.); the Institute of Surgical Pathology, University Medical Center Freiburg, Germany (P.B.); the Department of Surgery, University Medical Center Schleswig-Holstein–Campus Lübeck, Lübeck, Germany (B.K., T.K.); Comprehensive Cancer Center Augsburg, Faculty of Medicine, University of Augsburg, Augsburg, Germany (R.C.); the Department of General and Visceral Surgery, University Medical Center Freiburg, Freiburg, Germany (S.U.); the Department of General, Visceral, and Thoracic Surgery, University Medical Center Hamburg–Eppendorf, Hamburg, Germany (J.R.I.); the Department of Gastrointestinal Surgery, IRCCS San Raffaele Scientific Institute and San Raffaele Vita-Salute Universi...
Dirk Waldschmidt
Stefan Boeck
Nicolas Moosmann
Anke C. Reinacher-Schick
COLOPREDICT Platform and Department of Hematology, Oncology and Palliative Care, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany
Henriette Golcher
Werner Adler
Rainer Fietkau, MD, Sabine Semrau, MD, and Annett Kallies, PhD, Department of Radiation Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Erlangen, Germany, National Center for Tumor Diseases (NCT), NCT WERA, a Partnership Between DKFZ, and the Universities and University Hospitals in Wurzburg, Erlangen, Germany; Werner Adler, PhD, Department of Medical Informatics, Biometry and Epidemiology, University of Erlangen-Nurnberg, Erlangen, Germany, Helmut Oettle, MD, Department of Hematology, Oncology, and Tumor Immunology, Charité—Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany
Sabine Semrau
Dorota Lubgan
Annett Kallies
Rainer Fietkau, MD, Sabine Semrau, MD, and Annett Kallies, PhD, Department of Radiation Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Erlangen, Germany, National Center for Tumor Diseases (NCT), NCT WERA, a Partnership Between DKFZ, and the Universities and University Hospitals in Wurzburg, Erlangen, Germany; Werner Adler, PhD, Department of Medical Informatics, Biometry and Epidemiology, University of Erlangen-Nurnberg, Erlangen, Germany, Helmut Oettle, MD, Department of Hematology, Oncology, and Tumor Immunology, Charité—Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany
Markus Hecht
Institute of Organic Chemistry
Iris Tischoff
Andrea Tannapfel
COLOPREDICT Platform and Institute of Pathology, Ruhr-University, Bochum, Germany
Benjamin Frey
Helmut Oettle
Rainer Fietkau, MD, Sabine Semrau, MD, and Annett Kallies, PhD, Department of Radiation Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Erlangen, Germany, National Center for Tumor Diseases (NCT), NCT WERA, a Partnership Between DKFZ, and the Universities and University Hospitals in Wurzburg, Erlangen, Germany; Werner Adler, PhD, Department of Medical Informatics, Biometry and Epidemiology, University of Erlangen-Nurnberg, Erlangen, Germany, Helmut Oettle, MD, Department of Hematology, Oncology, and Tumor Immunology, Charité—Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany