Neoadjuvant chemoradiotherapy with or without panitumumab in patients with wild-type KRAS, locally advanced rectal cancer (LARC): a randomized, multicenter, phase II trial SAKK 41/07

作者：Helbling D^*; Bodoky G; Gautschi O; Sun H; Bosman F; Gloor B; Burkhard R; Winterhalder R; Madlung A; Rauch D; Saletti P; Widmer L; Borner M; Baertschi D; Yan P; Benhattar J; Leibundgut E O; Bougel S; Koeberle D

来源：Annals of Oncology, 2013, 24(3): 718-725.

DOI：10.1093/annonc/mds519

• capecitabine
• chemoradiotherapy
• panitumumab
• radiotherapy
• rectal cancer
• wild-type KRAS

Background: We conducted a randomized, phase II, multicenter study to evaluate the anti-epidermal growth factor receptor (EGFR) mAb panitumumab (P) in combination with chemoradiotherapy (CRT) with standard-dose capecitabine as neoadjuvant treatment for wild-type KRAS locally advanced rectal cancer (LARC).
Patients and methods: Patients with wild-type KRAS, T3-4 and/or N+ LARC were randomly assigned to receive CRT with or without P (6 mg/kg). The primary end-point was pathological near-complete or complete tumor response (pNC/CR), defined as grade 3 (pNCR) or 4 (pCR) histological regression by Dworak classification (DC).
Results: Forty of 68 patients were randomly assigned to P + CRT and 28 to CRT. pNC/CR was achieved in 21 patients (53%) treated with P + CRT [95% confidence interval (Cl) 36%-69%] versus 9 patients (32%) treated with CRT alone (95% Cl: 16%-52%). pCR was achieved in 4 (10%) and 5 (18%) patients, and pNCR in 17 (43%) and 4 (14%) patients. In immunohistochemical analysis, most DC 3 cells were not apoptotic. The most common grade >= 3 toxic effects in the P + CRT/CRT arm were diarrhea (10%/6%) and anastomotic leakage (15%/4%).
Conclusions: The addition of panitumumab to neoadjuvant CRT in patients with KRAS wild-type LARC resulted in a high pNC/CR rate, mostly grade 3 DC. The results of both treatment arms exceeded prespecified thresholds. The addition of panitumumab increased toxicity.

• 出版日期2013-3