| General information |
| Database: | DB00264 |
| Objective: | Combining cisplatin or cetuximab with radiation improves overall survival (OS) of patients with stage III or IV head and neck carcinoma (HNC). Cetuximab plus platinum regimens also increase OS in metastatic HNC. The Radiation Therapy Oncology Group launched a phase III trial to test the hypothesis that adding cetuximab to the radiationcisplatin platform improves progression free survival (PFS). |
| Authors: | Ang KK, et al |
| Title: | Randomizedphase III trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III to IV head and neck carcinoma: RTOG 0522. |
| Journal: | J Clin Oncol. |
| Year: | 2014 |
| PMID: | 25154822 |
| Trial Design |
| Clinical Trial Id: | NCT00265941 |
| Agent: | cetuximab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | head and neck cancer |
| Cancer Subtype: | advanced squamous cell carcinoma of the oropharynx, hypopharynx, or larynx |
| Therapy Type: | com |
| Therapeutic Combination Type: | 3 |
| Therapeutic Combination Content: | accelerated radiation+ cisplatin¡Àcetuximab |
| Study Type: | a randomizedphase III trial |
| Key Patients Feature: | Eligible patients had untreated, histologically confirmed, stage III or IV (T2N23M0 or T34, any N, M0) squamous cell carcinoma of the oropharynx, hypopharynx, or larynx; Zubrod performance status 0 to 1; age more than and equal to 18 years; any tobacco status; and adequate bone marrow, hepatic, and renal functions. |
| Biomarker: | p16 status, EGFR expression |
| Biomark Analysis: | Patients with p16positive oropharyngeal carcinoma (OPC), compared with patients with p16negative OPC, had better 3year probability of PFS (72.8% v. 49.2%, respectively; P < .001) and OS (85.6% v. 60.1%, respectively; P < .001), but tumor epidermal growth factor receptor (EGFR) expression did not distinguish outcome |
| Control Group Info: | radiation and cisplatin without (arm A) or with (arm B) cetuximab |
| Treatment Info: | patients were randomly assigned to receive radiation and cisplatin without (arm A) or with (arm B) cetuximab. Accelerated radiotherapy regimens included 72 Gy in 42 fractions given over 6 weeks, using twiceaday irradiation for 12 treatment days as previously reported. Cisplatin dose was 100 mg/m2 on days 1 and 22 of radiotherapy.Cisplatin dose was 100 mg/m2 on days 1 and 22 of radiotherapy. |
| Primary End Point: | PFS, OS, toxicity rates |
| Secondary End Point: | NA |
| Patients Number: | 891 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 3year PFS (arm A vs. arm B)(61.2% v. 58.9%, respectively; P =0.76); patients with p16positive oropharyngeal carcinoma (OPC), compared with patients with p16negative OPC, had better 3year probability of PFS (72.8% v. 49.2%, respectively; P <0.001) |
| Median OS A vs. C: | No differences were found between arms A and B in 30day mortality (1.8% v. 2.0%, respectively; P =0.81); 3year OS (72.9% v. 75.8%, respectively; P =o.32); patients with p16positive oropharyngeal carcinoma (OPC), compared with patients with p16negative OPC, had better 3year probability of OS (85.6% v. 60.1%, respectively; P <0.001). |
| Adverse Event(agent arm): | more grade 3 to 4 radiation mucositis (43.2% v. 33.3%, respectively), rash, fatigue, anorexia, and hypokalemia, but not more late toxicity in arm A than arm B |
| Conclusions: | Adding cetuximab to radiationcisplatin did not improve outcome and hence should not be prescribed routinely. PFS and OS they were higher in patients with p16positive OPC, but outcomes did not differ by EGFR expression. |