| General information |
| Database: | DB00352 |
| Objective: | herapy of recurrent/metastatic squamous cell carcinoma of the head and neck results in median progression free survival (PFS) of 2 months. These cancers are rich in epidermal growth factor receptor (EGFR). They wished to determine whether the addition of cetuximab, which inhibits activation of EGFR, would improve PFS. |
| Authors: | Burtness B, et al |
| Title: | Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: an Eastern Cooperative Oncology Group study. |
| Journal: | J Clin Oncol. |
| Year: | 2005 |
| PMID: | 16314626 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | cetuximab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | head and neck cancer |
| Cancer Subtype: | advanced head and neck squamous cell carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | cisplatin plus cetuximab |
| Study Type: | randomized, multicenter, placebocontrolled studyphase III Randomized Trial |
| Key Patients Feature: | patients were eligible if they had measurable or nonmeasurable but assessable squamous cell carcinoma of the head and neckregion, which was recurrent after locoregional therapy or metastatic. If the only site of measurable disease was a previouslyirradiated area, documented progression of disease and a 4weekperiod since the conclusion of radiotherapy or biopsyprovenresidual disease at least 8 weeks from the completion of radiationtherapy were required. No induction or adjuvant chemotherapywithin 3 months of study entry, or prior chemotherapy for recurrent or metastatic disease was permitted, and patients must haverecovered from the effects of any major surgery. patients wererequired to be more than 2 years disease free from any priormalignancy, except curatively treated basal or squamous cell carcinoma of the skin or carcinomainsitu of the cervix. They mightnot have had evidence of active infection or been receiving treatment for infection at the time of enrollment. patients were required to have ECOG performance status of0 or 1, to be 18 years of age, and to be without history of brainmetastases or evidence of hypersensitivity to murine proteins.Adequate organ function was required, manifest by absolute neutrophil count 1, 500/mL, platelet count 100, 000/mL, hemoglobin 10 gm/dL, serum creatinine 1.2 mg% or creatinineclearance 50 mL/min, total bilirubin 1.5 mg/100 mL, and AST, ALT, and alkaline phosphatase 2 times the institution¡¯supper limit of normal. Pregnant and lactating women were excluded, and women of childbearing potential must have had anegative serum pregnancy test. |
| Biomarker: | EGFR expression status |
| Biomark Analysis: | Enhancement of response was greater for patients with EGFR staining present in less than 80% of cells. |
| Control Group Info: | A:cisplatin plus placebo B:cisplatin plus cetuximab |
| Treatment Info: | patients were randomly assigned to receive cisplatin every 4 weeks, with weekly cetuximab (arm A) or placebo (arm B). Tumor tissue was assayed for EGFR expression by immunohistochemistry. |
| Primary End Point: | PFS. |
| Secondary End Point: | response rate, toxicity, overall survival, and correlation of EGFR with clinical end points. |
| Patients Number: | 117 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Median PFS was 2.7 months for arm B and 4.2 months for arm A. The hazard ratio for progression of arm A to arm B was 0.78 (95% CI, 0.54to 1.12). Median overall survival was 8.0 months for arm B and 9.2 months for arm A (P .21). The hazard ratio for survival by skin toxicity in cetuximabtreated patients was 0.42 (95%CI, 0.21 to 0.86). Objective response rate was 26% for arm A and 10% for arm B (P .03).Enhancement of response was greater for patients with EGFR staining present in less than 80% of cells |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 2.7 months for arm B and 4.2 months for arm A. |
| Median OS A vs. C: | 8.0 months for arm B and 9.2 months for arm A (P=0 .21). |
| Adverse Event(agent arm): | Grade 3 or 4 toxicity was observed in 90% of patients on arm A and 73% of patients on arm B (P =0.02). The principal toxicities observed were those associated with use of cisplatin at 100 mg/m2, including fatigue (17% in arm A v 14% in arm B; P =0 .61), nausea (24% v 19%;P=0.50), vomiting (17% in each arm; P=0.81), hyponatremia (26% v 28%; P =0 .83), neutropenia (30% v 14%; P=0.04), and thrombocytopenia (11% v 4%; P=0.14).Hypomagnesemia was more common among patients on arm A than on arm B (14% v 0%; P =0 .006). |
| Conclusions: | Addition of cetuximab to cisplatin significantly improves response rate. There was a survival advantage for the development of rash. progression free and overall survival they were not significantly improved by the addition of cetuximab in this study. |