Nele Boeckx1, Reija Koukakis2, Ken Op de Beeck1, Christian Rolfo3, Guy Van Camp4, Salvatore Siena5, Josep Tabernero6, Jean-Yves Douillard7, Thierry André8, Marc Peeters9. 1. Center for Oncological Research, University of Antwerp, Wilrijk, Belgium; Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium. 2. Biostatistics, Amgen Ltd, Uxbridge, United Kingdom. 3. Center for Oncological Research, University of Antwerp, Wilrijk, Belgium; Department of Oncology, Antwerp University Hospital, Edegem, Belgium. 4. Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium. 5. Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy; Dipartimento di Oncologia e Emato-Oncologia, Università degli Studi di Milano, Milan, Italy. 6. Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain. 7. Institut de Cancérologie de l'Ouest (ICO) René Gauducheau, Nantes, France. 8. Hôpital Saint Antoine, Sorbonne Universités, UPMC Paris 06 and GERCOR, Paris, France. 9. Center for Oncological Research, University of Antwerp, Wilrijk, Belgium; Department of Oncology, Antwerp University Hospital, Edegem, Belgium. Electronic address: marc.peeters@uza.be.
Abstract
BACKGROUND: The primary tumor location has a prognostic impact in metastatic colorectal cancer (mCRC). We report the results from retrospective analyses assessing the effect of tumor location on prognosis and efficacy of second- and later-line panitumumab treatment in patients with RAS wild-type (WT) mCRC and on prognosis in all lines of treatment in patients with RAS mutant (MT) mCRC. PATIENTS AND METHODS: RAS WT data (n = 483) from 2 randomized phase III panitumumab trials (ClinicalTrials.gov identifiers, NCT00339183 and NCT00113763) were analyzed for treatment outcomes stratified by tumor location. The second analysis assessed the effect of tumor location in RAS MT patients (n = 1205) from 4 panitumumab studies (ClinicalTrials.gov identifiers, NCT00364013, NCT00819780, NCT00339183, and NCT00113763). Primary tumors located in the cecum to transverse colon were coded as right-sided; those located from the splenic flexure to the rectum were coded as left-sided. RESULTS: Of all patients, the tumor location was ascertained for 83% to 88%; 71% to 77% of patients had left-sided tumors. RAS WT patients with right-sided tumors did worse for all efficacy parameters compared with those with left-sided tumors. The patients with left-sided tumors had better outcomes with panitumumab than with the comparator treatment. Because of the low patient numbers, no conclusions could be drawn for right-sided mCRC. The prognostic effect of tumor location on survival was unclear for RAS MT patients. CONCLUSION: These retrospective analyses have confirmed that RAS WT right-sided mCRC is associated with a poor prognosis, regardless of the treatment. RAS WT patients with left-sided tumors benefitted from the addition of panitumumab in second or later treatment lines. Further research is warranted to determine the optimum management of right-sided mCRC and RAS MT tumors.
BACKGROUND: The primary tumor location has a prognostic impact in metastatic colorectal cancer (mCRC). We report the results from retrospective analyses assessing the effect of tumor location on prognosis and efficacy of second- and later-line panitumumab treatment in patients with RAS wild-type (WT) mCRC and on prognosis in all lines of treatment in patients with RAS mutant (MT) mCRC. PATIENTS AND METHODS: RAS WT data (n = 483) from 2 randomized phase III panitumumab trials (ClinicalTrials.gov identifiers, NCT00339183 and NCT00113763) were analyzed for treatment outcomes stratified by tumor location. The second analysis assessed the effect of tumor location in RAS MT patients (n = 1205) from 4 panitumumab studies (ClinicalTrials.gov identifiers, NCT00364013, NCT00819780, NCT00339183, and NCT00113763). Primary tumors located in the cecum to transverse colon were coded as right-sided; those located from the splenic flexure to the rectum were coded as left-sided. RESULTS: Of all patients, the tumor location was ascertained for 83% to 88%; 71% to 77% of patients had left-sided tumors. RAS WT patients with right-sided tumors did worse for all efficacy parameters compared with those with left-sided tumors. The patients with left-sided tumors had better outcomes with panitumumab than with the comparator treatment. Because of the low patient numbers, no conclusions could be drawn for right-sided mCRC. The prognostic effect of tumor location on survival was unclear for RAS MT patients. CONCLUSION: These retrospective analyses have confirmed that RAS WT right-sided mCRC is associated with a poor prognosis, regardless of the treatment. RAS WT patients with left-sided tumors benefitted from the addition of panitumumab in second or later treatment lines. Further research is warranted to determine the optimum management of right-sided mCRC and RAS MT tumors.
Authors: Mohamed E Salem; Francesca Battaglin; Richard M Goldberg; Alberto Puccini; Anthony F Shields; David Arguello; W Michael Korn; John L Marshall; Axel Grothey; Heinz-Josef Lenz Journal: Oncologist Date: 2019-12-17
Authors: Nelleke P M Brouwer; Dave E W van der Kruijssen; Niek Hugen; Ignace H J T de Hingh; Iris D Nagtegaal; Rob H A Verhoeven; Miriam Koopman; Johannes H W de Wilt Journal: Ann Surg Oncol Date: 2019-12-02 Impact factor: 5.344
Authors: D M Le; S Ahmed; S Ahmed; B Brunet; J Davies; C Doll; M Ferguson; N Ginther; V Gordon; T Hamilton; P Hebbard; R Helewa; C A Kim; R Lee-Ying; H Lim; J M Loree; J P McGhie; K Mulder; J Park; D Renouf; R P W Wong; A Zaidi; T Asif Journal: Curr Oncol Date: 2019-12-01 Impact factor: 3.677
Authors: Elena Elez; Carles Pericay; Manuel Valladares-Ayerbes; Inmaculada Bando; Maria Jose Safont; Javier Gallego; Cristina Grávalos; Antonio Arrivi; Alfredo Carrato; Verónica Conde; Maria José Ortiz; Carlos López; Beatriz Alonso; Inmaculada Ruiz de Mena; Eduardo Díaz-Rubio; Josep Tabernero; Enrique Aranda Journal: Br J Cancer Date: 2019-07-31 Impact factor: 7.640
Authors: Nikhil Chauhan; Mary F Mulcahy; Riad Salem; Al B Benson Iii; Eveline Boucher; Janet Bukovcan; David Cosgrove; Chantal Laframboise; Robert J Lewandowski; Fayaz Master; Bassel El-Rayes; Jonathan R Strosberg; Daniel Y Sze; Ricky A Sharma Journal: JMIR Res Protoc Date: 2019-01-17