| General information |
| Database: | DB00510 |
| Objective: | To evaluate the efficacy and toxicity of combined treatment with two targeted agents, an antibody against vascular endothelial growth factor (bevacizumab) and an epidermal growth factor receptor tyrosine kinase inhibitor (erlotinib), in the treatment of patients with metastatic clearcell renal carcinoma. |
| Authors: | Hainsworth JD, et al |
| Title: | Treatment of metastatic renal cell carcinoma with a combination of bevacizumab and erlotinib. |
| Journal: | J Clin Oncol. |
| Year: | 2005 |
| PMID: | 16204015 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | bevacizumab and erlotinib
|
| Target: | NA
|
| Cancer Type: | renal cell carcinoma |
| Cancer Subtype: | advanced renal cell carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | bevacizumab+erlotinib |
| Study Type: | multicenter, phase II trial |
| Key Patients Feature: | To be eligible for this trial, patients were required to haveprogressive, biopsyproven metastatic or locally recurrent unresectable clearcell renal carcinoma. If tumors had mixed histology, the clearcell component was required to comprise more than75% of the biopsy specimen. patients were required to have nephrectomy more than 30 days before initiating protocol treatmentexcept in situations in which extensive, symptomatic metastasesprecluded nephrectomy as a reasonable medical option. Patientswith metastatic disease at the time of nephrectomy were not required to have additional tumor progression before initiatingtreatment with bevacizumab/erlotinib. patients were allowed tohave received a maximum of one previous systemic regimen withimmunotherapy and/or chemotherapy for metastatic disease. Noprevious treatment with other EGF receptor inhibitors or antiangiogenesis agents (including thalidomide) was allowed. Patientswith brain metastases were eligible only if they had less than threemetastases, had completed surgical treatment or radiation therapymore than 8 weeks before study entry, and had no neurologicsymptoms or dexamethasone requirement at the time of studyentry. Additional entry criteria included Eastern CooperativeOncology Group (ECOG) performance status 0 or 1; measurablemetastatic lesions; absolute neutrophil count 1, 500/mL andplatelets 75, 000/mL; serum bilirubin 1.6 mg/dL; serum creatinine 2.0 mg/dL; no proteinuria; age 18 years; and no otheractive, serious medical problems. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | patients were treated with bevacizumab 10 mg/kg intravenously every 2 weeks and erlotinib 150 mg orally daily. patients were reevaluated after 8 weeks of treatment; patients who responded continued treatment until they experienced tumor progression. |
| Primary End Point: | ORR, PFS, OS, toxicities. |
| Secondary End Point: | NA |
| Patients Number: | 63 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Fifteen (25%) of 59 assessable patients (95% CI, 16% to 37%) had objective responses totreatment, and an additional 36 patients (61%) had stable disease after 8 weeks oftreatment. Only eight patients¡¯ (14%) disease had progressed at this time point |
| Disease Control Rate: | 0.86 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | The median and 1year progression free survivals were 11 months and 43%, respectively. |
| Median OS A vs. C: | After a median followup of 15 months, median survival has not been reached; survival at 18 months was 60%. |
| Adverse Event(agent arm): | Treatment was generally well tolerated; only two patients discontinued treatment because of toxicity (skin rash). Grade 1/2 skin rash and diarrhea were the most frequent treatmentrelated toxicities. |
| Conclusions: | The combination of bevacizumab and erlotinib is an effective and welltolerated treatment for patients with advanced renal cell carcinoma. The efficacy of these two drugs in combination suggests that targeting of separate pathways critical to tumor growth and dissemination may achieve results superior to either drug as a single agent. Additional development of this and other combinations of targeted agents is warranted. |