PURPOSE: This trial investigated the addition of panitumumab to triplet chemotherapy with fluorouracil/folinic acid, oxaliplatin, and irinotecan (FOLFOXIRI) in a two-to-one randomized, controlled, open-label, phase II trial in patients with untreated RAS wild-type (WT) metastatic colorectal cancer. PATIENTS AND METHODS: The primary end point was objective response rate (ORR) according to RECIST (version 1.1). The experimental arm (modified FOLFOXIRI [mFOLFOXIRI] plus panitumumab) was considered active if the ORR was ≥ 75%. The experimental ORR was compared with an estimated ORR of 60% based on historical data, verified by a randomized control group (FOLFOXIRI). The power of the trial was 80%, with a potential type I error of 0.05. Secondary end points included secondary resection rate, toxicity, progression-free survival, and overall survival. RESULTS: A total of 63 patients were randomly assigned to the experimental arm and 33 patients to the control arm. The ORR of the mFOLFOXIRI plus panitumumab arm exceeded 75% and was higher when compared with that of FOLFOXIRI (87.3% v 60.6%; odds ratio, 4.469; 95% CI, 1.61 to 12.38; P = .004). The secondary resection rate was improved with the addition of panitumumab (33.3% v 12.1%; P = .02). Progression-free survival was similar in the study arms, whereas overall survival showed a trend in favor of the panitumumab-containing arm (hazard ratio for death, 0.67; 95% CI, 0.41 to 1.11; P = .12). CONCLUSION: The addition of panitumumab to mFOLFOXIRI in patients with RAS WT metastatic colorectal cancer improved the ORR and rate of secondary resection of metastases and represents a treatment option in selected and fit patients in need of highly active first-line therapy. Future studies should determine whether the addition of panitumumab to mFOLFOXIRI prolongs survival.
RCT Entities:
PURPOSE: This trial investigated the addition of panitumumab to triplet chemotherapy with fluorouracil/folinic acid, oxaliplatin, and irinotecan (FOLFOXIRI) in a two-to-one randomized, controlled, open-label, phase II trial in patients with untreated RAS wild-type (WT) metastatic colorectal cancer. PATIENTS AND METHODS: The primary end point was objective response rate (ORR) according to RECIST (version 1.1). The experimental arm (modified FOLFOXIRI [mFOLFOXIRI] plus panitumumab) was considered active if the ORR was ≥ 75%. The experimental ORR was compared with an estimated ORR of 60% based on historical data, verified by a randomized control group (FOLFOXIRI). The power of the trial was 80%, with a potential type I error of 0.05. Secondary end points included secondary resection rate, toxicity, progression-free survival, and overall survival. RESULTS: A total of 63 patients were randomly assigned to the experimental arm and 33 patients to the control arm. The ORR of the mFOLFOXIRI plus panitumumab arm exceeded 75% and was higher when compared with that of FOLFOXIRI (87.3% v 60.6%; odds ratio, 4.469; 95% CI, 1.61 to 12.38; P = .004). The secondary resection rate was improved with the addition of panitumumab (33.3% v 12.1%; P = .02). Progression-free survival was similar in the study arms, whereas overall survival showed a trend in favor of the panitumumab-containing arm (hazard ratio for death, 0.67; 95% CI, 0.41 to 1.11; P = .12). CONCLUSION: The addition of panitumumab to mFOLFOXIRI in patients with RAS WT metastatic colorectal cancer improved the ORR and rate of secondary resection of metastases and represents a treatment option in selected and fit patients in need of highly active first-line therapy. Future studies should determine whether the addition of panitumumab to mFOLFOXIRI prolongs survival.
Authors: Dominik Paul Modest; Meinolf Karthaus; Stefan Fruehauf; Ullrich Graeven; Lothar Müller; Alexander Otto König; Ludwig Fischer von Weikersthal; Karel Caca; Albrecht Kretzschmar; Eray Goekkurt; Siegfried Haas; Annika Kurreck; Arndt Stahler; Swantje Held; Armin Jarosch; David Horst; Anke Reinacher-Schick; Stefan Kasper; Volker Heinemann; Sebastian Stintzing; Tanja Trarbach Journal: J Clin Oncol Date: 2021-09-17 Impact factor: 44.544
Authors: Nancy E Kemeny; Joanne F Chou; Marinela Capanu; Walid K Chatila; Hongyu Shi; Francisco Sanchez-Vega; Thomas Peter Kingham; Louise Catherine Connell; William R Jarnagin; Michael I D'Angelica Journal: Ann Surg Date: 2021-08-01 Impact factor: 13.787
Authors: Javier Molina-Cerrillo; María San Román; Javier Pozas; Teresa Alonso-Gordoa; Miguel Pozas; Elisa Conde; Marta Rosas; Enrique Grande; María Laura García-Bermejo; Alfredo Carrato Journal: Cancers (Basel) Date: 2020-06-14 Impact factor: 6.639
Authors: Jack Martin; Angelica Petrillo; Elizabeth C Smyth; Nadeem Shaida; Samir Khwaja; H K Cheow; Adam Duckworth; Paula Heister; Raaj Praseedom; Asif Jah; Anita Balakrishnan; Simon Harper; Siong Liau; Vasilis Kosmoliaptsis; Emmanuel Huguet Journal: World J Clin Oncol Date: 2020-10-24