Entry Detail
| General information | |
| Database: | DB00271 |
| Objective: | Afatinib is an oral, irreversible ErbB family blocker that has shown activity in epidermal growth factor receptor (EGFR)mutated lung cancer. They hypothesized that the agent would have greater antitumor activity compared with cetuximab in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients, whose disease has progressed after platinumcontaining therapy. |
| Authors: | Seitheyrt TY, et al |
| Title: | A randomized, phase II study of afatinib versus cetuximab in metastatic or recurrent squamous cell carcinoma of the head and neck. |
| Journal: | Ann Oncol. |
| Year: | 2014 |
| PMID: | 24928832 |
| Trial Design | |
| Clinical Trial Id: | NA |
| Agent: | afatinib |
| Target: | Receptor proteintyrosine kinase erbB2 Epidermal growth factor receptor |
| Cancer Type: | head and neck cancer |
| Cancer Subtype: | advanced head and neck squamous cell carcinoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | An openlabel, randomized, phase II trial |
| Key Patients Feature: | Eligible patients (aged more than and equal to 18 years) at 43 centers had pathologically confirmed R/M HNSCC, progression following any line of prior platinumbased therapy, measurable disease, an Eastern Cooperative Oncology Group performance status (ECOG PS) of less than and equal to 1, adequate endorgan function, |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | cetuximab |
| Treatment Info: | patients were randomized (1 : 1) to either afatinib (50 mg/day) or cetuximab (250 mg/m(2)/week) until disease progression or intolerable adverse events (AEs) (stage I), with optional crossover (stage II). |
| Primary End Point: | tumor shrinkage |
| Secondary End Point: | NA |
| Patients Number: | 124 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | In stage I, mean tumor shrinkage by IR/ICR was 10.4%/16.6% with afatinib and 5.4%/10.1% with cetuximab (P = 0.46/0.30). Objective response rate was 16.1%/8.1% with afatinib and 6.5%/9.7% with cetuximab (IR/ICR). |
| Disease Control Rate: | Comparable disease control rates were observed with afatinib (50%) and cetuximab (56.5%) by IR; similar results were seen by ICR. In stage II, disease control rate (IR/ICR) was 38.9%/33.3% with afatinib and 18.8%/18.8% with cetuximab. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | In stage I, median PFS by ICR for afatinib and cetuximabtreated patients was similar; 13.0 versus 15.0 weeks [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.62-1.38, P = 0.71; For stage II, median PFS for patients who crossed over to afatinib was 9.3 and 5.7 weeks for those crossing to cetuximab (HR 0.64, 95% CI 0.38-1.05, P = 0.08 |
| Median OS A vs. C: | Median OS was 35.9 weeks for afatinib and 47.1 weeks for cetuximabtreated patients during stage I and II (HR 1.06, 95% CI 0.70-1.62, P = 0.78) |
| Adverse Event(agent arm): | Most common grade more than and equal to 3 drugrelated AEs (DRAEs) were rash/acne (18% versus 8.3%), diarrhea (14.8% versus 0%), and stomatitis/mucositis (11.5% versus 0%) with afatinib and cetuximab, respectively. |
| Conclusions: | Afatinib showed antitumor activity comparable to cetuximab in RM HNSCC in this exploratoryphase II trial, although more patients on afatinib discontinued treatment due to AEs. Sequential EGFRErbB treatment with afatinib and cetuximab provided sustained clinical benefit in patients after crossover, suggesting a lack of crossresistance. |