Volker Heinemann1, Ludwig Fischer von Weikersthal2, Thomas Decker3, Alexander Kiani4, Florian Kaiser5, Salah-Edin Al-Batran6, Tobias Heintges7, Christoph Lerchenmüller8, Christoph Kahl9, Gernot Seipelt10, Frank Kullmann11, Markus Moehler12, Werner Scheithauer13, Swantje Held14, Lisa Miller-Phillips15, Dominik Paul Modest15, Andreas Jung16, Thomas Kirchner16, Sebastian Stintzing17. 1. Department of Medicine III, University Hospital, Ludwig Maximilian University (LMU), Munich, Germany. Volker.heinemann@med.uni-muenchen.de. 2. Gesundheitszentrum St. Marien, Amberg, Germany. 3. Onkologie Ravensburg, Ravensburg, Germany. 4. Klinik Herzoghöhe, Bayreuth, Germany. 5. Oncological Practice, Landshut, Germany. 6. Institute of Clinical Cancer Research at Krankenhaus Nordwest University Cancer Center, Frankfurt, Germany. 7. Department of Medicine II, Städtische Kliniken Neuss, Neuss, Germany. 8. Oncological Practice, Münster, Germany. 9. Department of Haematology and Oncology, Städtisches Klinikum Magdeburg, Magdeburg, Germany. 10. Oncological Practice, Bad Soden, Germany. 11. Department of Medicine I, Klinikum Weiden, Weiden, Germany. 12. Department of Medicine II, University Hospital, Johannes Gutenberg University Mainz, Mainz, Germany. 13. Department of Internal Medicine I and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. 14. ClinAssess GmbH, Leverkusen, Germany. 15. Department of Medicine III, University Hospital, Ludwig Maximilian University (LMU), Munich, Germany. 16. Institute of Pathology, University of Munich, Munich, Germany. 17. Division of Hematology, Oncology, and Tumor Immunology (CCM), Department of Medicine, Charité Universitaetsmedizin Berlin, Berlin, Germany.
Abstract
BACKGROUND: Cetuximab plus FOLFIRI improved overall survival compared with bevacizumab plus FOLFIRI in KRAS wild-type metastatic colorectal cancer (mCRC) in FIRE-3, but no corresponding benefit was found for progression-free survival. This analysis aimed to determine whether cetuximab improves response and survival versus bevacizumab among response-evaluable patients receiving first-line FOLFIRI for RAS wild-type mCRC and the effect of primary tumour side on outcomes. METHODS: The intent-to-treat population included 593 patients with KRAS exon 2 wild-type mCRC. Further testing identified 400 patients with extended RAS wild-type disease; of these, 352 (88%) who received ≥3 cycles of therapy and had ≥1 post-baseline scan were evaluable for response and constituted the per-protocol population (169 cetuximab and 183 bevacizumab). Patients received 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) with either weekly cetuximab or biweekly bevacizumab given on day 1 of each 14-day cycle until response, progression or toxicity occurred. The primary endpoint was the objective response rate (ORR) in the per-protocol population. Secondary endpoints included overall survival (OS) and progression-free survival (PFS). The effect of primary tumour location was evaluated. RESULTS: Median OS in the RAS wild-type population was 31 vs 26 months in the cetuximab and bevacizumab groups, respectively (HR 0.76, P = 0.012). In the per-protocol population, outcomes favoured cetuximab for ORR (77% vs 65%, P = 0.014) and median OS (33 vs 26 months, HR 0.75, P = 0.011), while PFS was comparable between groups. The advantage of cetuximab over bevacizumab occurred only in patients with left-sided primary tumours. CONCLUSIONS: FOLFIRI plus cetuximab resulted in a significantly higher ORR and longer OS compared to FOLFIRI plus bevacizumab among patients with left-sided tumours. The superior response associated with cetuximab may particularly benefit patients with symptomatic tumours or borderline-resectable metastases. CLINICALTRIALS. GOV IDENTIFIER: NCT00433927.
BACKGROUND: Cetuximab plus FOLFIRI improved overall survival compared with bevacizumab plus FOLFIRI in KRAS wild-type metastatic colorectal cancer (mCRC) in FIRE-3, but no corresponding benefit was found for progression-free survival. This analysis aimed to determine whether cetuximab improves response and survival versus bevacizumab among response-evaluable patients receiving first-line FOLFIRI for RAS wild-type mCRC and the effect of primary tumour side on outcomes. METHODS: The intent-to-treat population included 593 patients with KRAS exon 2 wild-type mCRC. Further testing identified 400 patients with extended RAS wild-type disease; of these, 352 (88%) who received ≥3 cycles of therapy and had ≥1 post-baseline scan were evaluable for response and constituted the per-protocol population (169 cetuximab and 183 bevacizumab). Patients received 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) with either weekly cetuximab or biweekly bevacizumab given on day 1 of each 14-day cycle until response, progression or toxicity occurred. The primary endpoint was the objective response rate (ORR) in the per-protocol population. Secondary endpoints included overall survival (OS) and progression-free survival (PFS). The effect of primary tumour location was evaluated. RESULTS: Median OS in the RAS wild-type population was 31 vs 26 months in the cetuximab and bevacizumab groups, respectively (HR 0.76, P = 0.012). In the per-protocol population, outcomes favoured cetuximab for ORR (77% vs 65%, P = 0.014) and median OS (33 vs 26 months, HR 0.75, P = 0.011), while PFS was comparable between groups. The advantage of cetuximab over bevacizumab occurred only in patients with left-sided primary tumours. CONCLUSIONS: FOLFIRI plus cetuximab resulted in a significantly higher ORR and longer OS compared to FOLFIRI plus bevacizumab among patients with left-sided tumours. The superior response associated with cetuximab may particularly benefit patients with symptomatic tumours or borderline-resectable metastases. CLINICALTRIALS. GOV IDENTIFIER: NCT00433927.
Authors: Annabel H S Alig; Volker Heinemann; Michael Geissler; Ludwig Fischer von Weikersthal; Thomas Decker; Kathrin Heinrich; Swantje Held; Lena Weiss; Laura E Fischer; Nicolas Moosmann; Arndt Stahler; Ivan Jelas; Annika Kurreck; Jobst C von Einem; Anke C Reinacher-Schick; Andrea Tannapfel; Clemens Giessen-Jung; Sebastian Stintzing; Dominik P Modest Journal: Cancers (Basel) Date: 2022-01-21 Impact factor: 6.639
Authors: Deepak Vangala; Swetlana Ladigan; Sven T Liffers; Soha Noseir; Abdelouahid Maghnouj; Tina-Maria Götze; Berlinda Verdoodt; Susanne Klein-Scory; Laura Godfrey; Martina K Zowada; Mario Huerta; Daniel L Edelstein; Jaime Martinez de Villarreal; Miriam Marqués; Jörg Kumbrink; Andreas Jung; Tobias Schiergens; Jens Werner; Volker Heinemann; Sebastian Stintzing; Doris Lindoerfer; Ulrich Mansmann; Michael Pohl; Christian Teschendorf; Christiane Bernhardt; Heiner Wolters; Josef Stern; Selami Usta; Richard Viebahn; Jacob Admard; Nicolas Casadei; Stefan Fröhling; Claudia R Ball; Jens T Siveke; Hanno Glimm; Andrea Tannapfel; Wolff Schmiegel; Stephan A Hahn Journal: Genome Med Date: 2021-07-16 Impact factor: 11.117