Trial S0205 实验证实西妥昔单抗联合吉西他滨治疗局部晚期胰腺癌不能延长总生存期——JCO最新报道

Phase III Study Comparing Gemcitabine Plus Cetuximab Versus Gemcitabine in Patients With Advanced Pancreatic Adenocarcinoma: Southwest Oncology Group–Directed Intergroup Trial S0205

From the Wayne State University/Karmanos Cancer Institute, Detroit, MI; Southwest Oncology Group Statistical Center; Puget Sound Oncology Consortium; Swedish Cancer Institute, Seattle, WA; Oregon Health and Science University, Portland, OR; Memorial Sloan-Kettering Cancer Center, New York; University of Rochester, Rochester, NY; Metro Minnesota Community Clinical Oncology Program (CCOP), St Louis Park, MN; Carle Cancer Center, Urbana, IL; Southeast Cancer Control Consortium CCOP, Winston-Salem, NC; Center for Oncology Research and Treatment, Dallas; The University of Texas M.D. Anderson Cancer Center, Houston, TX; James P. Wilmot, University of Cincinnati, Cincinnati, OH; Ameripath, Phoenix, AZ; Cancer Care Manitoba, St Boniface General Hospital, Winnepeg, Manitoba; University of British Columbia; and British Columbia Cancer Agency, Vancouver, British Columbia, Canada.

Corresponding author: Philip A. Philip, MD, PhD, Wayne State University, Karmanos Cancer Institute, GI Oncology, 4100 John R St, 4th Fl, HWCRC, Detroit, MI 48201; e-mail: philipp@karmanos.org .

Purpose Patients with advanced pancreas cancer present with disease that is poorly responsive to conventional therapies. Preclinical and early clinical evidence has supported targeting the epidermal growth factor receptor (EGFR) signaling pathway in patients with pancreas cancer. This trial was conducted to evaluate the contribution of an EGFR-targeted agent to standard gemcitabine therapy. Cetuximab is a monoclonal antibody against the ligand-binding domain of the receptor.

Patients and Methods Patients with unresectable locally advanced or metastatic pancreatic adenocarcinoma were randomly assigned to receive gemcitabine alone or gemcitabine plus cetuximab. The primary end point was overall survival. Secondary end points included progression-free survival, time to treatment failure, objective response, and toxicity.

Results A total of 745 eligible patients were accrued. No significant difference was seen between the two arms of the study with respect to the median survival time (6.3 months for the gemcitabine plus cetuximab arm v 5.9 months for the gemcitabine alone arm; hazard ratio = 1.06; 95% CI, 0.91 to 1.23; P = .23, one-sided). Objective responses and progression-free survival were similar in both arms of the study. Although time to treatment failure was longer in patients on gemcitabine plus cetuximab (P = .006), the difference in length of treatment was only 2 weeks longer in the combination arm. Among patients who were studied for tumoral EGFR expression, 90% were positive, with no treatment benefit detected in this patient subset.

Conclusion In patients with advanced pancreas cancer, the anti-EGFR monoclonal antibody cetuximab did not improve the outcome compared with patients treated with gemcitabine alone. Alternate targets other than EGFR should be evaluated for new drug development.