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Exploring the effect of primary tumor sidedness on therapeutic efficacy across treatment lines in patients with metastatic colorectal cancer: analysis of FIRE-3 (AIOKRK0306)

PURPOSE: To assess the impact of primary tumor sidedness on outcome of patients with metastatic colorectal cancer (mCRC) across treatment lines. PATIENTS AND METHODS: Patients of the FIRE-3 trial (initial FOLFIRI plus either cetuximab or bevacizumab) were separately evaluated according to primary tu...

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Detalles Bibliográficos
Autores principales: Modest, Dominik Paul, Stintzing, Sebastian, von Weikersthal, Ludwig Fischer, Decker, Thomas, Kiani, Alexander, Vehling-Kaiser, Ursula, Al-Batran, Salah-Eddin, Heintges, Tobias, Kahl, Christoph, Seipelt, Gernot, Kullmann, Frank, Scheithauer, Werner, Moehler, Markus, Holch, Julian Walter, von Einem, Jobst Christian, Held, Swantje, Heinemann, Volker
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5739676/
https://www.ncbi.nlm.nih.gov/pubmed/29285289
http://dx.doi.org/10.18632/oncotarget.22396
Descripción
Sumario:PURPOSE: To assess the impact of primary tumor sidedness on outcome of patients with metastatic colorectal cancer (mCRC) across treatment lines. PATIENTS AND METHODS: Patients of the FIRE-3 trial (initial FOLFIRI plus either cetuximab or bevacizumab) were separately evaluated according to primary tumor site differentiating left-sided (LPT) from right-sided primary tumors (RPT). Efficacy (i.e. progression-free survival (PFS2nd) and overall survival (OS2nd) of second-line therapy) was evaluated by Kaplan-Meier method and compared by log rank test as well as Cox regression analyses. All analyses were also reported according to drug sequences. RESULTS: 411 of 592 patients (69%) with KRAS exon 2 wild-type tumors received 2nd-line therapy has and had available information on primary tumor location, of those 309 patients (75%) presented with LPT. In patients with LPT, PFS2nd was markedly longer than in patients with RPT (6.0 months [95% CI 5.5-6.5] versus 3.8 months [95% CI 2.5-5.2], hazard ratio: 0.61 [95% CI 0.47-0.78], P<0.001). Differences in PFS2nd between study-arms were evident in patients with LPT, but not in patients with RPT (Cox model interaction test, P=0.12). Consistent observations were also made for OS2nd. CONCLUSION: This retrospective analysis of FIRE-3 indicates that efficacy of second-line therapy was significantly greater in patients with left-sided tumors as compared to right-sided tumors. This difference was driven by superior activity of second-line regimens of the initial cetuximab-arm as compared to the initial bevacizumab-arm in left-sided tumors. Our observations confirm the strong prognostic value of primary tumor location in second-line therapy of mCRC.