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Panitumumab as a radiosensitizing agent in KRAS wild-type locally advanced rectal cancer

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Mardjuadi, Feby [UCL] Carrasco, Javier [UCL] Coche, Jean-Charles Sempoux, Christine [UCL] Jouret-Mourin, Anne [UCL] Scalliet, Pierre [UCL] Humblet, Yves [UCL] Van den Eynde, Marc [UCL] Moxhon, Anne [UCL] Canon, Jean-Luc [UCL] Machiels, Jean-Pascal [UCL]

Our goal was to optimize the radiosensitizing potential of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies, when given concomitantly with preoperative radiotherapy in KRAS wild-type locally advanced rectal cancer (LARC). Based on pre-clinical studies conducted by our group, we designed a phase II trial in which panitumumab (6 mg/kg/q2 weeks) was combined with preoperative radiotherapy (45 Gy in 25 fractions) to treat cT3-4/N + KRAS wild-type LARC. The primary endpoint was complete pathologic response (pCR) (H0 = 5 %, H1 = 17 %, α = 0.05, β = 0.2). From 19 enrolled patients, 17 (89 %) were evaluable for pathology assessment. Although no pCR was observed, seven patients (41 %) had grade 3 Dworak pathological tumor regression. The regimen was safe and was associated with 95 % of sphincter-preservation rate. No NRAS, BRAF, or PI3KCA mutation was found in this study, but one patient (5 %) showed loss of PTEN expression. The quantification of plasma EGFR ligands during treatment showed significant upregulation of plasma TGF-α and EGF following panitumumab administration (p < 0.05). At surgery, patients with important pathological regression (grade 3 Dworak) had higher plasma TGF-α (p = 0.03) but lower plasma EGF (p = 0.003) compared to those with grade 0-2 Dworak. Our study suggests that concomitant panitumumab and preoperative radiotherapy in KRAS wild-type LARC is feasible and results in some tumor regression. However, pCR rate remained modest. Given that the primary endpoint of our study was not reached, we remain unable to recommend the use of panitumumab as a radiosensitizer in KRAS wild-type LARC outside a research setting.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès libre
Publication date 2015
Language Anglais
Journal information "Targeted Oncology : biotherapies for the clinicians in oncology" - Vol. 10, no. 3, p. 375-383 (2015)
Peer reviewed yes
Publisher Springer France ((France) Paris)
issn 1776-2596
e-issn 1776-260X
Publication status Publié
Affiliations UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie
UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie
UCL - (SLuc) Service d'anatomie pathologique
UCL - (SLuc) Unité d'oncologie médicale
UCL - (SLuc) Service de radiothérapie oncologique
UCL - (SLuc) Centre du cancer
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Bibliographic reference Mardjuadi, Feby ; Carrasco, Javier ; Coche, Jean-Charles ; Sempoux, Christine ; Jouret-Mourin, Anne ; et. al. Panitumumab as a radiosensitizing agent in KRAS wild-type locally advanced rectal cancer. In: Targeted Oncology : biotherapies for the clinicians in oncology, Vol. 10, no. 3, p. 375-383 (2015)
Permanent URL http://hdl.handle.net/2078.1/151838