| General information |
| Database: | DB00030 |
| Objective: | The antiEGFR monoclonal antibodies panitumumab and cetuximab are effective in patients with chemotherapyrefractory wildtype KRAS exon 2 metastatic colorectal cancer. They assessed the efficacy and toxicity of panitumumab versus cetuximab in these patients. |
| Authors: | Price TJ, et al |
| Title: | Panitumumab versus cetuximab in patients with chemotherapyrefractory wildtype KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre, openlabel, noninferiorityphase 3 study. |
| Journal: | Lancet Oncol. |
| Year: | 2014 |
| PMID: | 24739896 |
| Trial Design |
| Clinical Trial Id: | NCT01001377 |
| Agent: | panitumumab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | KRAS wildtype metastatic colorectal cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a randomised, openlabel, phase III headtohead study |
| Key Patients Feature: | patients (from centres in North America, South America, Europe, Asia, Africa, and Australia) aged 18 years or older with chemotherapyrefractory metastatic colorectal cancer, an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less, and wildtype KRAS exon 2 status. |
| Biomarker: | wildtype KRAS exon 2 |
| Biomark Analysis: | as in the conclusion |
| Control Group Info: | cetuximab |
| Treatment Info: | Using a computergenerated randomisation sequence, they assigned patients (1:1; stratified by geographical region and ECOG performance status, with a permuted block method) to receive panitumumab (6 mg/kg once every 2 weeks) or cetuximab (initial dose 400 mg/m(2); 250 mg/m(2) once a week thereafter). |
| Primary End Point: | overall survival assessed for noninferiority . The primary analysis included patients who received one or more dose of panitumumab or cetuximab, analysed per allocated treatment. |
| Secondary End Point: | NA |
| Patients Number: | 999 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | For the primary analysis of overall survival, panitumumab was noninferior to cetuximab (Z score 3.19; p=0.0007). Median overall survival was 10.4 months (95% CI 9.411.6) with panitumumab and 10.0 months (9.311.0) with cetuximab (HR 0.97; 95% CI 0.841.11). Panitumumab retained 105.7% (81.9129.5) of the effect of cetuximab on overall survival seen in this study. |
| Adverse Event(agent arm): | The incidence of adverse events of any grade and grade 34 was similar across treatment groups. Grade 34 skin toxicity occurred in 62 (13%) patients given panitumumab and 48 (10%) patients given cetuximab. The occurrence of grade 34 infusion reactions was lotheyr with panitumumab than with cetuximab (one [<0.5%] patient vs nine [2%] patients), and the occurrence of grade 34 hypomagnesaemia was higher in the panitumumab group (35 [7%] vs 13 [3%]). they recorded one treatmentrelated fatal adverse event: a lung infection in a patient given cetuximab. |
| Conclusions: | Our findings show that panitumumab is noninferior to cetuximab and that these agents provide similar overall survival benefit in this population of patients. Both agents had toxicity profiles that were to be expected. In view of the consistency in efficacy and toxicity seen, small but meaningful differences in the rate of grade 34 infusion reactions and differences in dose scheduling can guide physician choice of antiEGFR treatment. |