Effect of Primary Tumor Location on Second- or Later-line Treatment Outcomes in Patients With RAS Wild-type Metastatic Colorectal Cancer and All Treatment Lines in Patients With RAS Mutations in Four Randomized Panitumumab Studies

Nele Boeckx (1, 2) , Reija Koukakis , Ken Op de Beeck (2, 1) , Christian Rolfo (1, 2) , Guy van Camp (1, 2) , Salvatore Siena (3) , Josep Tabernero (4, 5) , Jean-Yves Douillard (6) , Thierry André (7, 8) , Marc Peeters (2, 1)

1 UZA - Antwerp University Hospital [Edegem]
2 UA - University of Antwerp
3 UNIMI - Università degli Studi di Milano = University of Milan
4 Vall d'Hebron University Hospital [Barcelona]
5 UAB - Universitat Autònoma de Barcelona = Autonomous University of Barcelona = Universidad Autónoma de Barcelona
6 UNICANCER/ICO - Institut de Cancérologie de l'Ouest [Angers/Nantes]
7 GERCOR - Cooperator Multidisciplinary Oncology Group
8 CHU Saint-Antoine [AP-HP]

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.

Mots clés: mCRC; RAS mutant; RAS WT; Treatment lines; Tumor location

Domaines: Cancer; Hépatologie et Gastroentérologie; Immunothérapie

Nele Boeckx, Reija Koukakis, Ken Op de Beeck, Christian Rolfo, Guy van Camp, et al.. Effect of Primary Tumor Location on Second- or Later-line Treatment Outcomes in Patients With RAS Wild-type Metastatic Colorectal Cancer and All Treatment Lines in Patients With RAS Mutations in Four Randomized Panitumumab Studies. Clinical Colorectal Cancer, 2018, 17 (3), pp.170-178.e3. ⟨10.1016/j.clcc.2018.03.005⟩. ⟨hal-02109307⟩