Jean-Yves Douillard1, Salvatore Siena2, Marc Peeters3, Reija Koukakis4, Jan-Henrik Terwey5, Josep Tabernero6. 1. ICO Centre René Gauducheau, 44805 St Herblain, France. Electronic address: jean-yves.douillard@ico.unicancer.fr. 2. Ospedale Niguarda Ca' Granda, Niguarda Cancer Center, Piazza Ospedale Maggiore 3, Milan 20162, Italy. Electronic address: Salvatore.Siena@OspedaleNiguarda.it. 3. Antwerp University Hospital Medical Oncology Center Antwerp (MOCA) and Antwerp University, Wilrijkstraat 10, B-2650 Edegem, Belgium. Electronic address: Marc.Peeters@uza.be. 4. Biostatistics, Amgen Ltd, 1 Uxbridge Business Park, Sanderson Road, Uxbridge, Middlesex UB8 1DH, United Kingdom. Electronic address: reijak@amgen.com. 5. Medical Development - Oncology, Amgen (Europe) GmbH, Dammstrasse 23, 6301 Zug, Switzerland. Electronic address: jan-henrik.terwey@amgen.com. 6. Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, P. Vall d'Hebron 119-129, 08035 Barcelona, Spain. Electronic address: jtabernero@vhio.net.
Abstract
BACKGROUND: Tumour shrinkage (TS) increases the possibility of resection in metastatic colorectal cancer (mCRC) and may improve tumour-related symptoms. Here we report prespecified secondary response-related end-points and exploratory TS/resection outcomes for patients with RAS wild-type (WT) tumours (no mutations in KRAS/NRAS exons 2/3/4) from the PRIME study (NCT00364013). METHODS: PRIME was a randomised phase 3 study comparing first-line panitumumab+FOLFOX4 versus FOLFOX4 in mCRC patients. Tumour response analyses were conducted to compare response rates and their impact on survival outcomes. RESULTS: Overall, 505 patients had RAS WT mCRC. More patients receiving panitumumab+FOLFOX4 versus FOLFOX4 had ⩾30% (59% versus 38%; P<0.001) or ⩾20% (72% versus 57%; P<0.001) TS at week 8 (early TS); consistent TS benefits were observed over the first ∼40weeks of treatment. Objective response rate (P=0.003), duration of response (P=0.0027), depth of response (P=0.0149), progression-free survival (PFS; P=0.0015) and overall survival (OS; P=0.0057) were improved in the panitumumab+FOLFOX4 group. Both early TS and resection were associated with improved PFS and OS. 2-year OS rates for patients who did (n=64) versus did not (n=441) undergo resection were 88% versus 40%; 2-year OS rates for patients who did (n=45) versus did not (n=460) undergo complete resection were 96% versus 41%. CONCLUSIONS: More patients receiving panitumumab+FOLFOX4 versus FOLFOX4 had ⩾30% or ⩾20% TS at week 8; PFS and OS were also improved with panitumumab+FOLFOX4. The clinical value of achieving early TS in mCRC warrants further investigation.
RCT Entities:
BACKGROUND:Tumour shrinkage (TS) increases the possibility of resection in metastatic colorectal cancer (mCRC) and may improve tumour-related symptoms. Here we report prespecified secondary response-related end-points and exploratory TS/resection outcomes for patients with RAS wild-type (WT) tumours (no mutations in KRAS/NRAS exons 2/3/4) from the PRIME study (NCT00364013). METHODS: PRIME was a randomised phase 3 study comparing first-line panitumumab+FOLFOX4 versus FOLFOX4 in mCRC patients. Tumour response analyses were conducted to compare response rates and their impact on survival outcomes. RESULTS: Overall, 505 patients had RAS WT mCRC. More patients receiving panitumumab+FOLFOX4 versus FOLFOX4 had ⩾30% (59% versus 38%; P<0.001) or ⩾20% (72% versus 57%; P<0.001) TS at week 8 (early TS); consistent TS benefits were observed over the first ∼40weeks of treatment. Objective response rate (P=0.003), duration of response (P=0.0027), depth of response (P=0.0149), progression-free survival (PFS; P=0.0015) and overall survival (OS; P=0.0057) were improved in the panitumumab+FOLFOX4 group. Both early TS and resection were associated with improved PFS and OS. 2-year OS rates for patients who did (n=64) versus did not (n=441) undergo resection were 88% versus 40%; 2-year OS rates for patients who did (n=45) versus did not (n=460) undergo complete resection were 96% versus 41%. CONCLUSIONS: More patients receiving panitumumab+FOLFOX4 versus FOLFOX4 had ⩾30% or ⩾20% TS at week 8; PFS and OS were also improved with panitumumab+FOLFOX4. The clinical value of achieving early TS in mCRC warrants further investigation.
Authors: R García-Carbonero; R Vera; F Rivera; E Parlorio; M Pagés; E González-Flores; C Fernández-Martos; M Á Corral; R Bouzas; F Matute Journal: Clin Transl Oncol Date: 2016-05-20 Impact factor: 3.405
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: Salvatore Siena; Josep Tabernero; Gyorgy Bodoky; David Cunningham; Fernando Rivera; Paul Ruff; Jean Luc Canon; Reija Koukakis; Gaston Demonty; Guy Hechmati; Jean-Yves Douillard Journal: ESMO Open Date: 2016-03-31
Authors: Meinolf Karthaus; Ralf-Dieter Hofheinz; Laurent Mineur; Henry Letocha; Richard Greil; Josef Thaler; Eva Fernebro; Kelly S Oliner; Michael Boedigheimer; Brian Twomey; Ying Zhang; Gaston Demonty; Claus-Henning Köhne Journal: Br J Cancer Date: 2016-10-20 Impact factor: 7.640