| General information |
| Database: | DB00495 |
| Objective: | Elderly patients with metastatic renal cell carcinoma (mRCC) may require special treatment considerations, particularly when comorbidities are present. An understanding of the efficacy and safety of targeted agents in elderly patients with mRCC is essential to provide individualized therapy. |
| Authors: | Porta C, et al |
| Title: | Efficacy and safety of everolimus in elderly patients with metastatic renal cell carcinoma: an exploratory analysis of the outcomes of elderly patients in the RECORD1 Trial. |
| Journal: | Eur Urol. |
| Year: | 2012 |
| PMID: | 22297244 |
| Trial Design |
| Clinical Trial Id: | NCT00410124 |
| Agent: | everolimus
|
| Target: | Serine/threonineprotein kinase mTOR
|
| Cancer Type: | renal cell carcinoma |
| Cancer Subtype: | advanced renal cell carcinoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | A Randomized, Doubleblind, Placebocontrolled, Multicenterphase III Study |
| Key Patients Feature: | Patients with metastatic carcinoma and with histological or cytological confirmation of clear cell RCC (tissue from the original diagnosis of renal cell cancer is acceptable). The date of progression on sunitinib and/or sorafenib must be within 6 months. Patients may have received one or both agents Prior therapy with cytokines (i.e., IL2, Interferon) and/or VEGFligand inhibitors (i.e., bevacizumab) are permitted. Prior vaccine therapy in the adjuvant setting is permitted. Patients with at least one measurable lesion at baseline as per the Response evaluation criteria in solid tumors (RECIST) criteria, either on physical exam or as determined by Computer Tomography (CT) Scan or Magnetic Resonance Imaging (MRI). Patients with a Karnofsky Performance Status more than and equal to 70%. Adequate bone marrow, liver and renal function. Patients with a life expectancy more than and equal to 3 months. Women of childbearing potential must have had a negative serum or urine pregnancy test 48 hours prior to the administration of the first study treatment. Patients who give a written informed consent obtained according to local guidelines |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | Everolimus 10mg once daily (n=277) or placebo (n=139) |
| Treatment Info: | Everolimus 10mg once daily (n=277) or placebo (n=139) plus best supportive care. Treatment was continued until disease progression or unacceptable toxicity. |
| Primary End Point: | Median PFS, median overall survival (OS), and time to deterioration in Karnofsky performance status (TTDKPS); |
| Secondary End Point: | Other outcomes evaluated included reduction in tumor burden, overall response rate (ORR), and safety. |
| Patients Number: | 416 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Objective response rates were 2.7%, 3.8%, and 1.8% in patients more than and equal to 65 yr, more than and equal to 70 yr, and in all patients, respectively, with no responses observed in any group receiving placebo (Table 2). Consistent with the overall study population, no significant difference in median OS was observed in everolimustreated patients compared with those receiving placebo age more than and equal to 65 yr and more than and equal to 70 yr |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | median PFS with everolimus and placebo, respectively, was 5.4 mo versus 2.2 mo in patients more than and equal to 65 yr of age (hazard ratio [HR]: 0.33; 95% confidence interval [CI], 0.21-0.51; p < 0.001), 5.1 mo versus 1.9 mo in patients more than and equal to 70 yr of age (HR: 0.19; 95% CI, 0.09-0.37; p < 0.001), and 4.9 mo versus 1.9 mo in the overall study population (HR: 0.33; 95% CI, 0.25-0.43; p < 0.001). |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Everolimus was generally well tolerated in elderly patients, and most adverse events were grade 1 or 2 in severity. The toxicity profile of everolimus was generally similar in older patients and the overall population; however, peripheral edema, cough, rash, and diarrhea were reported more frequently in the elderly regardless of treatment. |
| Conclusions: | Everolimus is effective and tolerable in elderly patients with mRCC. When selecting targeted therapies in these patients, the specific toxicity profile of each agent and any patient comorbidities should be considered. |