| General information |
| Database: | DB00316 |
| Objective: | They evaluated combined targeting with cetuximab, an antiepidermal growth factor receptor (EGFR) monoclonal antibody, and bevacizumab, an antivascular endothelial growth factor (VEGF) monoclonal antibody, in squamous cell carcinoma of the head and neck (SCCHN). |
| Authors: | Argiris A, et al |
| Title: | Cetuximab and bevacizumab: preclinical data andphase II trial in recurrent or metastatic squamous cell carcinoma of the head and neck. |
| Journal: | Ann Oncol. |
| Year: | 2013 |
| PMID: | 22898037 |
| 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: | 1 |
| Therapeutic Combination Content: | Cetuximab and bevacizumab |
| Study Type: | phase II trial |
| Key Patients Feature: | age 18 or older with histologically orcytologically documented R/M SCCHN, not eligible for curative intentsurgical or radiation therapy, with measurable disease according toResponse Evaluation Criteria in Solid Tumors (RECIST) definitions [30]and Eastern Cooperative Oncology Group (EGOG) performance status0-2. No more than one prior adjuvant/neoadjuvant chemotherapy and/orconcomitant chemoradiotherapy regimen that may have included biologic/targeted agent and no more than 1 prior treatment (chemotherapy orbiologic/targeted) for R/M SCCHN was allowed. No prior treatment withEGFR or angiogenesis inhibitors was permitted. patients were required tohave absolute neutrophil count more than and equal to 1000 per ¦Ìl and platelet count more than and equal to 75 000per ¦Ìl, total bilirubin within normal range, AST and ALT less than and equal to 5 times theinstitutional upper limit of normal, creatinine clearance >60 ml/min, andurine protein to urine creatinine ratio of <1 |
| Biomarker: | epidermal growth factor (EGF), VEGF, PIGF, FGF a and b (FGFa, FGFb), HGF, granulocytecolony stimulating factor (GCSF), transforming growth factor alpha (TGFa), IL6, IL8, IP10, soluble EGFR, and soluble VEGFR (sVEGFR2). |
| Biomark Analysis: | transforming growth factor alpha, placentaderived growth factor, EGFR, VEGFR2 increased and VEGF decreased after treatment but did not correlate with treatment efficacy. |
| Control Group Info: | single arm |
| Treatment Info: | Patients with recurrent or metastatic SCCHN were treated with weekly cetuximab and bevacizumab, 15 mg/kg on day 1 given intravenously every 21 days, until disease progression. Analysis of tumor biomarkers and related serum cytokines was performed. |
| Primary End Point: | ORR; |
| Secondary End Point: | NA |
| Patients Number: | 46 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Cetuximab plus bevacizumab enhanced growth inhibition both in vitro and in vivo, and resulted in potent reduction in tumor vascularization. In the clinical trial, 46 eligible patients were enrolled. The objective response rate was 16% and the disease control rate 73%. The median progression free survival and overall survival were 2.8 and 7.5 months, respectively. Grade 34 adverse events were expected and occurred in less than 10% of patients. transforming growth factor alpha, placentaderived growth factor, EGFR, VEGFR2 increased and VEGF decreased after treatment but did not correlate with treatment efficacy. |
| Disease Control Rate: | 0.73 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 2.8 months (95% CI 2.7-4.2 months) |
| Median OS A vs. C: | 7.5 months (95% CI, 5.7-9.6 months) |
| Adverse Event(agent arm): | The most common drugrelated adverse event was rash. In addition to two cases of grade 3 bleeding, four patients had grade 2 hemorrhage and six patients grade 1 hemorrhage. Three patients developed grade 2 hypertension. Two patients died of aspiration pneumonia in the context of which one developed hypoxemia complicated by cardiac ischemia and the other acute renal failure. |
| Conclusions: | Cetuximab and bevacizumab are supported by preclinical observations and are well tolerated and active in previously treated patients with SCCHN. |