Open-Label Phase III Trial of Panitumumab Plus Best Supportive Care Compared With Best Supportive Care Alone in Patients With Chemotherapy-Refractory

Panitumumab is a fully human monoclonal antibody directed against the epidermal growth factor receptor (EGFR). We compared the activity of panitumumab plus best supportive care (BSC) to that of BSC alone in patients with metastatic colorectal cancer who had progressed after standard chemotherapy. Patients and Methods We randomly assigned 463 patients with 1 % or more EGFR tumor cell membrane staining, measurable disease, and radiologic documentation of disease progression during or within 6 months of most recent chemotherapy to panitumumab 6 mg/kg every 2 weeks plus BSC (n 231) or BSC alone (n 232). Tumor assessments by blinded central review were scheduled from week 8 until disease progression. The primary end point was progression-free survival (PFS). Secondary end points included objective response, overall survival (OS), and safety. BSC patients who progressed could receive panitumumab in a cross-over study. Results Panitumumab significantly prolonged PFS (hazard ratio [HR], 0.54; 95 % CI, 0.44 to 0.66, [P .0001]). Median PFS time was 8 weeks (95 % CI, 7.9 to 8.4) for panitumumab and 7.3 weeks (95 % CI, 7.1 to 7.7) for BSC. Mean (standard error) PFS time was 13.8 (0.8) weeks for panitumumab and 8.5 (0.5) weeks for BSC. Objective response rates also favored panitumumab over BSC; after a 12-month minimum follow-up, response rates were 10 % for panitumumab and 0 % for BSC (P .0001). No difference was observed in OS (HR, 1.00; 95 % CI, 0.82 to 1.22), which was confounded by similar activity of panitumumab after 76 % of BSC patients entered the cross-over study. Panitumumab was well tolerated. Skin toxicities, hypomagnesaemia, and diarrhea were the most common toxicities observed. No patients had grade 3/4 infusion reactions. Conclusion Panitumumab significantly improved PFS with manageable toxicity in patients with chemorefrac-tory colorectal cancer. J Clin Oncol 25:1658-1664. © 2007 by American Society of Clinical Oncolog