| General information |
| Database: | DB00035 |
| Objective: | Therapeutic antibodies targeting EGFR have activity in advanced colorectal cancer, but results from clinical trials are inconsistent and the population in which most benefit is derived is uncertain. Their aim was to assess the addition of panitumumab to irinotecan in pretreated advanced colorectal cancer. |
| Authors: | Seymour MT, et al |
| Title: | Panitumumab and irinotecan versus irinotecan alone for patients with KRAS wildtype, fluorouracilresistant advanced colorectal cancer (PICCOLO): a prospectively stratified randomised trial. |
| Journal: | Lancet Oncol |
| Year: | 2013 |
| PMID: | 23725851 |
| Trial Design |
| Clinical Trial Id: | ISRCTN93248876. |
| Agent: | panitumumab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | advanced colorectal cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Panitumumab + irinotecan |
| Study Type: | a prospectively stratified randomised trial |
| Key Patients Feature: | patients who had advanced colorectal cancer progressing after fluoropyrimidine treatment with or without oxaliplatin from 60 centres in the UK |
| Biomarker: | KRAS mutation |
| Biomark Analysis: | as in the conclusion |
| Control Group Info: | irinotecan alone |
| Treatment Info: | From June 10, 2008, in response to new data, the trial was amended to a prospectively stratified design, restricting panitumumab randomisation to patients with KRAS wildtype tumours; the results of the comparison between the irinotcan and IrPan groups are reported here. They used a computergenerated randomisation sequence to randomly allocate patients to either irinotecan or IrPan. Patients in both groups received 350 mg/m(2) intravenous irinotecan every 3 weeks (300 mg/m(2) if aged more than and equal to 70 years or a performance status of 2); patients in the IrPan group also received intravenous panitumumab 9 mg/kg every 3 weeks. |
| Primary End Point: | overall survival in KRAS wildtype patients who had not received previous EGFR targeted therapy, analysed by intention to treat. Tumour DNA was pyrosequenced for KRASc.146, BRAF, NRAS, and PIK3CA mutations, and predefined molecular subgroups were analysed for interaction with the effect of panitumumab. |
| Secondary End Point: | NA |
| Patients Number: | 460 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | a greater number of responses (79 [34%] patients vs 27 [12%]; p<0.0001) than did individuals in the irinotecan group. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | individuals in the IrPan group had longer progression free survival (0.78, 0.640.95; p=0.015) |
| Median OS A vs. C: | There was no difference in overall survival between groups (HR 1.01, 95% CI 0.831.23; p=0.91), |
| Adverse Event(agent arm): | Grade 3 or worse diarrhoea (64 [29%] of 219 patients vs 39 [18%] of 218 patients), skin toxicity (41 [19%] vs none), lethargy (45 [21]% vs 24 [11%]), infection (42 [19%] vs 22 [10%]) and haematological toxicity (48 [22%] vs 27 [12%]) were reported more commonly in the IrPan group than in the irinotecan group. They recorded five treatmentrelated deaths, two in the IrPan group and three in the irinotecan group. |
| Conclusions: | Adding panitumumab to irinotecan did not improve the overall survival of patients with wildtype KRAS tumours. Further refinement of molecular selection is needed for substantial benefits to be derived from EGFR targeting agents. |