A Phase 2 Clinical Trial of Panitumumab Monotherapy in Japanese Patients with Metastatic Colorectal Cancer

Aichi Cancer Center Hospital, Nagoya, Aichi, Japan.
Japanese Journal of Clinical Oncology (Impact Factor: 2.02). 04/2009; 39(5):321-6. DOI: 10.1093/jjco/hyp016
Source: PubMed


Panitumumab, a fully human monoclonal antibody targeting epidermal growth factor receptor (EGFR), has antitumor activity and an acceptable safety profile in patients with metastatic colorectal cancer (mCRC). This Phase 2 study evaluated efficacy, pharmacokinetics and safety of panitumumab in Japanese patients with mCRC who developed progressive disease during or after fluoropyrimidine, irinotecan and oxaliplatin chemotherapy.
Eligible patients had histologically proven colorectal adenocarcinoma and EGFR tumor expression in > or =1% of tumor cells by immunohistochemistry. Patients received panitumumab 6 mg/kg every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) per modified Response Evaluation Criteria in Solid Tumors (RECIST) by independent central review. Secondary endpoints included progression-free survival (PFS), overall survival (OS), pharmacokinetic parameters and incidence of adverse events.
Fifty-two patients received at least one dose of panitumumab. Seven patients had partial responses for a confirmed ORR of 13.5% (95% CI: 5.6, 25.8). Median PFS was 8.0 weeks (95% CI: 7.4, 11.4) and median OS was 9.3 months (95% CI: 7.1, 12.8). Panitumumab pharmacokinetics were consistent with prior studies in Japanese and non-Japanese patients. The most common treatment-related adverse events (all, worst grade 3) were acne (81%, 2%), dry skin (62%, 0%), rash (46%, 2%), paronychia (33%, 2%), pruritus (33%, 0%) and hypomagnesemia (33%, 0%). No adverse event of infusion reaction was reported by the investigators.
Panitumumab monotherapy was active in Japanese patients with chemotherapy-refractory mCRC, with pharmacokinetic and safety profiles similar to those seen in prior studies.

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Available from: Yasuo Hamamoto
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    • "The approval of panitumumab in Japan for use in combination therapy represents the first such approval in the world. However, because the number of Japanese individuals enrolled in the global clinical trials was relatively limited (13), the Japanese Ministry of Health, Labour and Welfare required the market authorization holders to conduct a post-marketing surveillance study, called All Cases Surveillance (18), as a condition of its approval to evaluate the safety and effectiveness of all Japanese patients treated with panitumumab. The main purpose of this study was to collect detailed information, particularly with regard to safety issues, on all panitumumab-treated patients; additionally, by evaluating a large number of patients, the study aimed to identify rare adverse drug reactions (ADRs), which are often undetectable in smaller clinical trials. "
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