TY - JOUR
T1 - Open-label phase 2 trial of first-line everolimus monotherapy in patients with papillary metastatic renal cell carcinoma
T2 - RAPTOR final analysis
AU - Escudier, Bernard
AU - Molinie, Vincent
AU - Bracarda, Sergio
AU - Maroto, Pablo
AU - Szczylik, Cezary
AU - Nathan, Paul
AU - Negrier, Sylvie
AU - Weiss, Claudia
AU - Porta, Camillo
AU - Grünwald, Viktor
AU - Albiges, Laurence
N1 - Publisher Copyright:
© 2016 Elsevier Ltd
PY - 2016/12/1
Y1 - 2016/12/1
N2 - Background Papillary histology accounts for 10–15% of renal cell carcinoma (RCC), and treatment options for patients with this subtype are limited. The RAPTOR (RAD001 in Advanced Papillary Tumor Program in Europe; ClinicalTrials.gov, NCT00688753) study evaluated first-line everolimus in patients with papillary metastatic RCC (mRCC). Methods This phase 2 trial enrolled previously untreated patients with type 1 or type 2 papillary mRCC. Papillary histology was confirmed by central review and was performed for every patient. Patients received oral everolimus 10 mg once daily until disease progression or unacceptable toxicity. The primary end-point was progression-free survival (PFS) rate at 6 months among the first 44 patients of the per protocol (PP) population. Secondary end-points included PFS, tumour response, overall survival (OS), and safety. Findings Analysis sets included safety (N = 92; 100%), intent-to-treat (ITT) (n = 88), and PP populations (n = 46). In the safety population, most patients were men (78%) and the mean age was 60 years (range 23–84). Papillary histology was confirmed in 78% of patients (type 1, 32%; type 2, 64%; missing information, 4%). PFS rate at 6 months was 34% (80% confidence interval [CI] 25–45). In the ITT population, median PFS was 4.1 months (95% CI 3.6–5.5), 65% of patients achieved stable disease, and median OS was 21.4 months (95% CI 15.4–28.4). Among patients with type 1 or type 2 histology, median PFS was 7.9 months (95% CI 2.1–11.0) and 5.1 months (95% CI 3.3–5.5), respectively, and median OS was 28.0 months (95% CI 7.6–not estimable) and 24.2 months (95% CI 15.8–32.8), respectively. Common grade >2 adverse events were asthenia (13%), anaemia (7%), and fatigue (5%). Interpretation Results of this large prospective study in papillary mRCC demonstrated that everolimus provides some clinical benefit to this patient population and highlight the need for central pathological review of this rare tumour.
AB - Background Papillary histology accounts for 10–15% of renal cell carcinoma (RCC), and treatment options for patients with this subtype are limited. The RAPTOR (RAD001 in Advanced Papillary Tumor Program in Europe; ClinicalTrials.gov, NCT00688753) study evaluated first-line everolimus in patients with papillary metastatic RCC (mRCC). Methods This phase 2 trial enrolled previously untreated patients with type 1 or type 2 papillary mRCC. Papillary histology was confirmed by central review and was performed for every patient. Patients received oral everolimus 10 mg once daily until disease progression or unacceptable toxicity. The primary end-point was progression-free survival (PFS) rate at 6 months among the first 44 patients of the per protocol (PP) population. Secondary end-points included PFS, tumour response, overall survival (OS), and safety. Findings Analysis sets included safety (N = 92; 100%), intent-to-treat (ITT) (n = 88), and PP populations (n = 46). In the safety population, most patients were men (78%) and the mean age was 60 years (range 23–84). Papillary histology was confirmed in 78% of patients (type 1, 32%; type 2, 64%; missing information, 4%). PFS rate at 6 months was 34% (80% confidence interval [CI] 25–45). In the ITT population, median PFS was 4.1 months (95% CI 3.6–5.5), 65% of patients achieved stable disease, and median OS was 21.4 months (95% CI 15.4–28.4). Among patients with type 1 or type 2 histology, median PFS was 7.9 months (95% CI 2.1–11.0) and 5.1 months (95% CI 3.3–5.5), respectively, and median OS was 28.0 months (95% CI 7.6–not estimable) and 24.2 months (95% CI 15.8–32.8), respectively. Common grade >2 adverse events were asthenia (13%), anaemia (7%), and fatigue (5%). Interpretation Results of this large prospective study in papillary mRCC demonstrated that everolimus provides some clinical benefit to this patient population and highlight the need for central pathological review of this rare tumour.
KW - Clinical trial
KW - Everolimus
KW - Non clear cell RCC
KW - Papillary RCC
KW - Phase 2
UR - http://www.scopus.com/inward/record.url?scp=84992723879&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2016.08.004
DO - 10.1016/j.ejca.2016.08.004
M3 - Article
C2 - 27680407
AN - SCOPUS:84992723879
SN - 0959-8049
VL - 69
SP - 226
EP - 235
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -