The Efficacy and Safety of Panitumumab Administered Concomitantly With FOLFIRI or Irinotecan in Second-Line Therapy for Metastatic Colorectal Cancer: The Secondary Analysis From STEPP (Skin Toxicity Evaluation Protocol With Panitumumab) by KRAS Status

The STEPP study found that preemptive treatment reduced skin toxicity compared with reactive treatment among patients receiving panitumumab in combination with irinotecan-based chemotherapy as second line therapy. This secondary analysis of the STEPP study indicates that panitumumab in combination with irinotecan-based chemotherapy has an acceptable toxicity profile in second-line therapy for mCRC; numerical differences trending in favor of patients with WT KRAS tumors were observed for most efficacy endpoints. Background: Panitumumab, a fully human monoclonal antibody targeting the epidermal growth factor receptor (EGFR), is used as monotherapy for chemorefractory metastatic colorectal cancer (mCRC) in patients with wild-type (WT) KRAS tumors. Although skin toxicities are the most common adverse events associated with EGFR inhibitors, the differences in efficacy and safety between pre-emptive and reactive skin treatment according to KRAS tumor status has not been reported. Patients and Methods: Eligible patients had mCRC with disease progression or unacceptable toxicity with first-line treatment containing fluoropyrimidine and oxaliplatin-based chemotherapy +/- bevacizumab. Patients were randomized 1: 1 to pre-emptive or reactive skin treatment (after skin toxicity developed). Patients received either panitumumab 6 mg/kg + FOLFIRI every 2 weeks or panitumumab 9 mg/kg + irinotecan every 3 weeks. Key study endpoints included overall response rate (ORR), overall survival, progression-free survival (PFS), and safety according to KRAS tumor status. Results: Eighty-seven (92%) of 95 enrolled patients had evaluable KRAS tumor status: 49 (56%) patients with WT and 38 (44%) patients with mutant (MT) KRAS tumors, respectively. The ORR was 16% and 8% for patients with WT and MT KRAS tumors, respectively. Median PFS was 5.5 and 3.3 months for patients with WT and MT KRAS tumors, respectively. The most commonly observed adverse events by KRAS tumor status included dermatitis acneiform and pruritus. Conclusion: Panitumumab in combination with irinotecan-based chemotherapy has an acceptable toxicity profile in second-line therapy for mCRC. Numerical differences trending in favor of the patients with WT KRAS tumors were observed for most efficacy endpoints. Clinical Colorectal Cancer, Vol. 10, No. 4, 333-9 (C) 2011 Elsevier Inc. All rights reserved.