Novel therapies are needed as an initial or salvage treatment for patients with metastatic or locally advanced RCC. This study aimed to assess the safety and efficacy of everolimus in patients with metastatic recurrent and/or unresectable clear cell RCC.
EVERMORE is an open-label, multicenter, single-arm, phase 2 study (NCT01206764) that enrolled patients aged ≥ 18 yrs with advanced and histologically confirmed clear or non-clear cell RCC. Everolimus 10 mg/d was administered orally, as a first line or after cytokine therapy, until disease progression (PD), unacceptable toxicity, or study discontinuation for any other reason. The primary endpoint was progression-free survival (PFS) rate over time. The secondary endpoints were disease control rate (DCR; stable disease + partial response [PR] + complete response [CR]), objective response rate (ORR), duration of response (DOR), overall survival (OS), and safety.
From 2009 to 2017, 142 patients with a mean age of 55.5 years from 10 countries were enrolled. Most of the patients (58.2%) have a clear cell adenocarcinoma as histology/cytology and 53.1% had stage IV disease at initial diagnosis. Of 142 patients, everolimus was received in 117 as first-line and in 25 as second-line treatment. The most common reason for early discontinuation of treatment was PD (n = 88, 62.0%). The median PFS for all assessed patients was 7.0 months (95% CI: 22.00, 37.29). The ORR was 12.0% (n = 17; 95% CI: 7.1, 18.5). The median DOR in patients who had either CR or PR was 39.0 months (n = 17). The DCR was 74.6% (n = 106; 95% CI: 66.7, 81.6). The median OS was not evaluable. The most commonly reported adverse events (AEs) of all grades were anemia (45.1%), stomatitis (29.6%), hyperglycemia (26.1%), and decreased appetite (22.5%). The most commonly reported serious AEs were pneumonia (n = 6), dyspnea (n = 4), urinary tract infection, decreased appetite, dehydration and diarrhea (n = 3 each). In the study, 33 deaths were reported, of which, 19 deaths were due to study indication.
The PFS and safety results of everolimus when administered in patients as first-line or after cytokine therapy are consistent with the previously published data (RECORD-3).
Clinical trial identification
Legal entity responsible for the study
Novartis Pharma AG.
Novartis Pharma AG.
D. Amokrane: Advisory board, Speaker or Grants for Clinical research: Novartis, Sanofi, Bayer, Ipsen, Amgen, Roche, Janssen, Pfizer MSD, Pierre Fabre. M. Ghosn: Grants-research support: Pfizer, Novartis. K. Slimane, V. Pilipovic: Employee and shareholder of Novartis. All other authors have declared no conflicts of interest.