| General information |
| Database: | DB00392 |
| Objective: | The combination of cisplatin and radiotherapy is a standard treatment for patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). Cetuximabradiotherapy is superior to radiotherapy alone in this population, validating epidermal growth factor receptor (EGFR) as a target. Erlotinib is a smallmolecule inhibitor of EGFR. Adding EGFR inhibition to standard cisplatinradiotherapy may improve efficacy. |
| Authors: | Martins RG, et al |
| Title: | Cisplatin and radiotherapy with or without erlotinib in locally advanced squamous cell carcinoma of the head and neck: a randomizedphase II trial. |
| Journal: | J Clin Oncol. |
| Year: | 2013 |
| PMID: | 23460709 |
| Trial Design |
| Clinical Trial Id: | NCT00410826 |
| Agent: | erlotinib
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | head and neck cancer |
| Cancer Subtype: | advanced head and neck squamous cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 3 |
| Therapeutic Combination Content: | Cisplatin and radiotherapy with or without erlotinib |
| Study Type: | Randomizedphase II Trial |
| Key Patients Feature: | Eligible patients had biopsyconfirmed stage III, IVA, or IVB SCCHN withidentified primary tumor in the nasopharynx (WHO type I), oral cavity, oropharynx, hypopharynx, or larynx; Eastern Cooperative Oncology Group(ECOG) performance status of 0 to 2, calculated creatinine clearance 55mL/min; adequate liver function; platelet count greater than 100, 000/dL; andneutrophil count 1, 250/dL. |
| Biomarker: | p16 and EGFR |
| Biomark Analysis: | Patients with tumors positive for p16 had a better outcome, with higher rates of CR according to local investigators (odds ratio [OR], 3.47; P=0.02) and favorable PFS (HR, 0.39; P=0.04).Superior PFS was observed for p16positive patients irrespective of tumor primary site. Only four patients had EGFRamplification, precluding addition alanalysis. |
| Control Group Info: | cisplatin 100 mg/m(2) on days 1, 22, and 43 combined with 70 Gy of radiotherapy (arm A) or the same chemoradiotherapy with erlotinib 150 mg per day, starting 1 week before radiotherapy and continued to its completion (arm B). |
| Treatment Info: | Patients with locally advanced SCCHN were randomly assigned to receive cisplatin 100 mg/m(2) on days 1, 22, and 43 combined with 70 Gy of radiotherapy (arm A) or the same chemoradiotherapy with erlotinib 150 mg per day, starting 1 week before radiotherapy and continued to its completion (arm B). |
| Primary End Point: | complete response rate (CRR), evaluated by central review. |
| Secondary End Point: | PFS |
| Patients Number: | 204 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Arm A had a CRR of 40% and arm B had a CRR of 52% (P = .08) when evaluated by central review. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Toxicities were dominated by those commonly seen with fulldosecisplatinandradiotherapy.Therewerenodifferencesin most common toxicities between the two arms, with one expected exception. Patients in arm B had more rash than patients in arm A (68% v 10%, respectively; P=0.001); 13% of patients in arm B had grade 3 rash (v 2% in arm A). Grade 3 or higher GI toxicity (predominantly mucositis, nausea, and vomiting) was the most common category of AE for both treatment arms. Serious AEs occurred.in 33% of patients in arm A and 40% in arm B. Treatment arms didnot differ in the rate of serious AEs, overall or for any specific AEcategory (P .20). |
| Conclusions: | Erlotinib did not increase the toxicity of cisplatin and radiotherapy in patients with locally advanced HNSCC but failed to significantly increase CRR or PFS. |