After completing this course, the reader will be able to:1. Add panitumumab (Vectibix™) to the armamentarium of drugs for colorectal cancer.2. Identify the patient group that is eligible for panitumumab therapy.3. Identify biologic agents that have activity in colorectal cancer.4. List the FDA criteria for the analysis of progression-free survival and for accelerated approval.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME ABSTRACTOn September 27, 2006, the U.S. Food and Drug Administration granted approval to panitumumab (Vectibix™, Amgen, Inc., Thousand Oaks, CA) for the treatment of patients with epidermal growth factor receptor (EGFR)-expressing, metastatic colorectal carcinoma with disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens. Panitumumab approval is based on the results of a single, open-label, randomized, multinational study that enrolled 463 patients with EGFR-expressing (at least 1؉ membrane staining in >1% of tumor cells) metastatic colorectal cancer. Patients were randomized to either best supportive care (BSC) alone or BSC plus panitumumab, 6 mg/kg i.v., every other week. The primary study endpoint was progression-free survival (PFS), determined by an independent review committee that was blinded as to treatment assignment. BSC patients who progressed were eligible to receive panitumumab.The study patients' median age was 62 years, with 40% aged >65; 63% were male, 99% were white, 86% had a baseline Eastern Cooperative Oncology Group performance status score of 0 or 1, and 67% had colon cancer. The median time from diagnosis of metastases was approximately 19 months and the median number of prior therapies was 2.4. The PFS duration was significantly longer among patients randomized to receive panitumumab in addition to BSC (n ‫؍‬ 231) compared with BSC alone (n ‫؍‬ 232). The median and mean PFS times were 56 and 96.4 days, respectively, for patients receiving panitumumab and 51 and 59.7 days, respectively, for patients receiving BSC alone. Nineteen partial responses (8%, 95% confidence interval [CI], 5.3%-12.5%) were observed in panitumumab treated patients. The median duration of response was 17 weeks (95% CI, 16 -25 weeks). Approximately 75% of patients in the BSC alone arm crossed over to receive panitumumab after disease progression. There was no difference in overall survival between the two study arms. The most common adverse events were skin rash, hypomagnesemia, paronychia, fatigue, abdominal pain,

Purpose: To describe the Food and Drug Administration review and marketing approval considerations for panitumumab (Vectibix) for the third-line treatment of patients with epidermal growth factor receptor^expressing metastatic colorectal carcinoma. Experimental Design: Food and Drug Administration reviewed a single, open-label, multicenter trial in which 463 patients with epidermal growth factor receptor^expressing metastatic colorectal cancer who had progressed on or following treatment with a regimen containing a fluoropyrimidine, oxaliplatin, and irinotecan were randomized (1:1) to receive best supportive care (BSC) with or without panitumumab (6 mg/kg every other week) administered until disease progression or intolerable toxicity. Progression and response were confirmed by an independent review committee masked to treatment assignment. At progression, patients in the BSC-alone arm were eligible to receive panitumumab. Results: Although median progression-free survival (PFS) was similar in both treatment arms (f8 weeks), the mean PFS was f50% longer among patients receiving panitumumab than among those receiving BSC alone (96 versus 60 days, respectively) and the objective response rate in patients receiving panitumumab was 8%. However, no difference in overall survival was shown between the two study arms. Conclusions: Panitumumab received accelerated approval based on improvement in PFS and an independently confirmed response rate of 8%, similar to that observed with other active agents at this advanced stage of disease. Confirmation of clinical benefit will be required for full approval. 5 This accelerated approval was based on the surrogate end point of tumor response. The clinical benefit (i.e., improved PFS or OS) of cetuximab in a study of 572 patients who had failed both irinotecan-and oxaliplatin-based chemotherapy regimens randomized (1:1) to receive best supportive care (BSC) with or without cetuximab administered as an i.v. infusion of 400 mg/m 2 on the first dose and then 250 mg/m 2 . Patients randomized to receive cetuximab showed a statistically 5