5 research outputs found
Everolimus in patients with metastatic renal cell carcinoma previously treated with bevacizumab: a prospective multicenter study CRAD001LRU02Tβ°
Everolimus is an orally administered inhibitor of the mammalian target of rapamycin (mTOR) recommended for patients with metastaticΒ renal cell carcinoma (mRCC) who progressed on previous vascular endothelial growth factor (VEGF) receptor-tyrosine kinase inhibitorΒ therapy. Efficacy of everolimus in patients who progressed on anti-VEGF monoclonal antibody bevacizumab is unknown. We did a multicenter prospective trial of everolimus in patients with mRCC whose disease had progressed on bevacizumab Β± interferon alpha (IFN). Patients with clear-cell mRCC which had progressed on bevacizumab Β± IFN received everolimus 10 mg once daily. The primary end point was the proportion of patients remaining progression-free for 56 days, and a two-stage Simon design was used, with 80 % power and an alpha risk of 5 %. This study is registered with ClinicalTrials.gov, number NCT02056587. From December 2011 to October 2013, a total of 37 patients (28 M, 9 F) were enrolled. Median age was 60.5 years (range 41-66), 11 % had Eastern Cooperative Oncology Group Performance Status (ECOG PS) > 2, and Memorial Sloan-Kettering Cancer Center (MSKCC) favorable/intermediate risk was 38/62 %. Five (14 %) patients had a confirmed partial response and 26 (70 %) patients had a stable disease. Median progression-free survival was 11.5 months (95 % CI, 8.8β14.2). Median overall survival was not reached. No grade 3 or 4 treatment-related toxicities were observed. The most common grade 2 adverse events were fatigue (19 %) and pneumonitis (8 %). Everolimus demonstrated a favorable toxicity profile and promising anti-tumor activity as a second-line therapy in metastatic renal cell carcinoma (RCC) patients previously treated with bevacizumab Β± IFN
ΠΡΡΠΈΠ»Π΅ΡΠ½ΡΡ ΠΎΠ±ΡΠ°Ρ Π²ΡΠΆΠΈΠ²Π°Π΅ΠΌΠΎΡΡΡ Π±ΠΎΠ»ΡΠ½ΡΡ ΠΌΠ΅ΡΠ°ΡΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΠΌ ΡΠ°ΠΊΠΎΠΌ ΠΏΠΎΡΠΊΠΈ, ΠΏΠΎΠ»ΡΡΠ°Π²ΡΠΈΡ ΡΠ²Π΅ΡΠΎΠ»ΠΈΠΌΡΡ ΠΏΡΠΈ ΠΏΡΠΎΠ³ΡΠ΅ΡΡΠΈΡΠΎΠ²Π°Π½ΠΈΠΈ Π½Π° ΡΠΎΠ½Π΅ Π»Π΅ΡΠ΅Π½ΠΈΡ Π±Π΅Π²Π°ΡΠΈΠ·ΡΠΌΠ°Π±ΠΎΠΌ: ΠΏΡΠΎΡΠΏΠ΅ΠΊΡΠΈΠ²Π½ΠΎΠ΅ ΠΌΠ½ΠΎΠ³ΠΎΡΠ΅Π½ΡΡΠΎΠ²ΠΎΠ΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ CRAD001LRU02T
Background. In a CRAD001LRU02T study of everolimus for metastatic renal cell carcinoma patients previously treated with bevacizumab Β±Β interferon, median overall survival (OS) was 17.4 months (95 % confidence interval 13.5β21.3 month).Objective of final analysis was to evaluate 5-year OS and long-term toxicity in this study.Materials and methods. Survival data were collected from 37 patients with bevacizumab-refractory metastatic renal cell carcinoma who received everolimus in a completed prospective multicenter study. Patients were predominantly male, 89 % had ECOG performance status of 0/1, 51 % received previous bevacizumab in combination with interferon, and 38/62% had MSKCC favorable/intermediate risk disease.Results. The 5-year survival rate was 16.2% (95 % confidence interval 14.1β18.3 %), with a median follow-up of 5 years. The 1-, and 3-year OS rates were 81.0 and 43.0 %, respectively. The median duration of second-line of everolimus was 315 (range 61β569) days. 11 (29.7 %) patients received third-line therapy with a median duration of 3.6 months. Confirmed objective tumor responses were seen in 5 (14.0 %) patients. 70.0 % (n = 26) patients had a stable disease. 1 (2.7 %) patient achieved complete response after 4 years of therapy. One (2.7 %) patientΒ discontinued everolimus therapy on their own accord due to relapse of systemic lupus erythematosus and one (2.7 %)Β patient had 14-days interruption of an everolimus therapy due to grade 3 hyperglycemia. No grade 4 treatment-related toxicity was found.Conclusions. Everolimus provided an estimated 5-year survival rate of 16.2 % for bevacizumab-resistant metastatic renal cell carcinoma. Prolonged everolimus was not associated with new types or increased severity of adverse events.ΠΠ²Π΅Π΄Π΅Π½ΠΈΠ΅. Π ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΈ CRAD001LRU02T ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΡΠ²Π΅ΡΠΎΠ»ΠΈΠΌΡΡΠ° Ρ Π±ΠΎΠ»ΡΠ½ΡΡ
ΠΌΠ΅ΡΠ°ΡΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΠΌ ΠΏΠΎΡΠ΅ΡΠ½ΠΎ-ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΠΌ ΡΠ°ΠΊΠΎΠΌ, ΠΏΠΎΠ»ΡΡΠ°Π²ΡΠΈΡ
ΡΠ°Π½Π΅Π΅ ΡΠ΅ΡΠ°ΠΏΠΈΡ Π±Π΅Π²Π°ΡΠΈΠ·ΡΠΌΠ°Π±ΠΎΠΌ Π² ΠΊΠΎΠΌΠ±ΠΈΠ½Π°ΡΠΈΠΈ Ρ ΠΈΠ½ΡΠ΅ΡΡΠ΅ΡΠΎΠ½ΠΎΠΌ ΠΈΠ»ΠΈ Π±Π΅Π· Π½Π΅Π³ΠΎ, ΠΌΠ΅Π΄ΠΈΠ°Π½Π° ΠΎΠ±ΡΠ΅ΠΉ Π²ΡΠΆΠΈΠ²Π°Π΅ΠΌΠΎΡΡΠΈ (ΠΠ) ΡΠΎΡΡΠ°Π²ΠΈΠ»Π° 17,4 ΠΌΠ΅Ρ (95 % Π΄ΠΎΠ²Π΅ΡΠΈΡΠ΅Π»ΡΠ½ΡΠΉ ΠΈΠ½ΡΠ΅ΡΠ²Π°Π» 13,5β21,3 ΠΌΠ΅Ρ).Π¦Π΅Π»Ρ ΡΠ°Π±ΠΎΡΡ β ΠΎΡΠ΅Π½ΠΊΠ° 5-Π»Π΅ΡΠ½Π΅ΠΉ ΠΠ ΠΈ ΠΎΡΠ΄Π°Π»Π΅Π½Π½ΠΎΠΉ ΡΠΎΠΊΡΠΈΡΠ½ΠΎΡΡΠΈ Π² ΡΡΠΎΠΌ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΈ.ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. ΠΠ°Π½Π½ΡΠ΅ ΠΏΠΎ ΠΠ Π±ΡΠ»ΠΈ ΠΏΠΎΠ»ΡΡΠ΅Π½Ρ Ρ 37 ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ², ΡΠ΅ΡΡΠ°ΠΊΡΠ΅ΡΠ½ΡΡ
ΠΊ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ Π±Π΅Π²Π°ΡΠΈΠ·ΡΠΌΠ°Π±ΠΎΠΌ ΠΈ ΠΏΠΎΠ»ΡΡΠΈΠ²ΡΠΈΡ
ΡΠ²Π΅ΡΠΎΠ»ΠΈΠΌΡΡ Π² ΡΠ°ΠΌΠΊΠ°Ρ
ΠΏΡΠΎΡΠΏΠ΅ΠΊΡΠΈΠ²Π½ΠΎΠ³ΠΎ ΠΌΠ½ΠΎΠ³ΠΎΡΠ΅Π½ΡΡΠΎΠ²ΠΎΠ³ΠΎ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ. ΠΠΎΠ»ΡΡΠΈΠ½ΡΡΠ²ΠΎ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² β ΠΌΡΠΆΡΠΈΠ½Ρ, 89 % Π±ΠΎΠ»ΡΠ½ΡΡ
ΠΈΠΌΠ΅Π»ΠΈ ΡΡΠ°ΡΡΡ ΠΏΠΎ ΡΠΊΠ°Π»Π΅ ECOG 0 / 1, 51 % ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² ΠΏΠΎΠ»ΡΡΠΈΠ»ΠΈ ΠΏΡΠ΅Π΄ΡΠ΅ΡΡΠ²ΡΡΡΡΡ ΡΠ΅ΡΠ°ΠΏΠΈΡ Π±Π΅Π²Π°ΡΠΈΠ·ΡΠΌΠ°Π±ΠΎΠΌ Π² ΠΊΠΎΠΌΠ±ΠΈΠ½Π°ΡΠΈΠΈ Ρ ΠΈΠ½ΡΠ΅ΡΡΠ΅ΡΠΎΠ½ΠΎΠΌ. ΠΠ»Π°Π³ΠΎΠΏΡΠΈΡΡΠ½ΡΠΉ ΠΏΡΠΎΠ³Π½ΠΎΠ· ΠΈΠΌΠ΅Π»ΠΈ 38 % Π±ΠΎΠ»ΡΠ½ΡΡ
, ΠΏΡΠΎΠΌΠ΅ΠΆΡΡΠΎΡΠ½ΡΠΉ β 62 %.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. ΠΡΠΈ ΠΌΠ΅Π΄ΠΈΠ°Π½Π΅ Π½Π°Π±Π»ΡΠ΄Π΅Π½ΠΈΡ 5 Π»Π΅Ρ 5-Π»Π΅ΡΠ½ΡΡ ΠΠ ΡΠΎΡΡΠ°Π²ΠΈΠ»Π° 16,2 % (95 % Π΄ΠΎΠ²Π΅ΡΠΈΡΠ΅Π»ΡΠ½ΡΠΉ ΠΈΠ½ΡΠ΅ΡΠ²Π°Π» 14,1β18,3 %),Β 1- ΠΈ 3-Π»Π΅ΡΠ½ΡΡ ΠΠ β 81,0 ΠΈ 43,0 % ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²Π΅Π½Π½ΠΎ. ΠΠ΅Π΄ΠΈΠ°Π½Π° ΠΏΡΠΎΠ΄ΠΎΠ»ΠΆΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ 2-ΠΉ Π»ΠΈΠ½ΠΈΠΈ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ ΡΠ²Π΅ΡΠΎΠ»ΠΈΠΌΡΡΠΎΠΌ ΡΠΎΡΡΠ°Π²ΠΈΠ»Π° 315 (61β569) ΡΡΡ. Π‘ ΠΌΠ΅Π΄ΠΈΠ°Π½ΠΎΠΉ Π΄Π»ΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ 3,6 ΠΌΠ΅Ρ 3-Ρ Π»ΠΈΠ½ΠΈΡ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ ΠΏΠΎΠ»ΡΡΠΈΠ»ΠΈ 11 (29,7 %) ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ². ΠΠΎΠ΄ΡΠ²Π΅ΡΠΆΠ΄Π΅Π½Π½ΡΠ΅ ΠΎΠ±ΡΠ΅ΠΊΡΠΈΠ²Π½ΡΠ΅ ΠΎΡΠ²Π΅ΡΡ ΠΎΡΠΌΠ΅ΡΠ΅Π½Ρ Ρ 5 (14,0 %) Π±ΠΎΠ»ΡΠ½ΡΡ
. Π‘ΡΠ°Π±ΠΈΠ»ΠΈΠ·Π°ΡΠΈΡ Π±ΠΎΠ»Π΅Π·Π½ΠΈ Π½Π°Π±Π»ΡΠ΄Π°Π»Π°ΡΡ Ρ 70,0 % (n = 26) ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ². ΠΠΎΠ»Π½ΠΎΠ³ΠΎ ΠΎΡΠ²Π΅ΡΠ° ΡΠΏΡΡΡΡ 4 Π³ΠΎΠ΄Π° ΡΠ΅ΡΠ°ΠΏΠΈΠΈ Π΄ΠΎΡΡΠΈΠ³ 1 (2,7 %) ΠΏΠ°ΡΠΈΠ΅Π½Ρ. ΠΠ·-Π·Π° ΠΎΠ±ΠΎΡΡΡΠ΅Π½ΠΈΡ ΡΠΈΡΡΠ΅ΠΌΠ½ΠΎΠΉ ΠΊΡΠ°ΡΠ½ΠΎΠΉ Π²ΠΎΠ»ΡΠ°Π½ΠΊΠΈ 1 (2,7 %) Π±ΠΎΠ»ΡΠ½ΠΎΠΉ ΠΏΠΎ ΡΠΎΠ±ΡΡΠ²Π΅Π½Π½ΠΎΠΌΡ ΠΆΠ΅Π»Π°Π½ΠΈΡ ΠΏΡΠ΅ΠΊΡΠ°ΡΠΈΠ» ΡΠ΅ΡΠ°ΠΏΠΈΡ ΡΠ²Π΅ΡΠΎΠ»ΠΈΠΌΡΡΠΎΠΌ ΠΈ 1 (2,7 %) ΠΏΠ°ΡΠΈΠ΅Π½Ρ ΠΈΠΌΠ΅Π» ΠΏΠ΅ΡΠ΅ΡΡΠ² Π² Π»Π΅ΡΠ΅Π½ΠΈΠΈ Π² ΡΠ΅ΡΠ΅Π½ΠΈΠ΅ 14 ΡΡΡ Π² ΡΠ²ΡΠ·ΠΈ Ρ ΡΠ°Π·Π²ΠΈΡΠΈΠ΅ΠΌ Π³ΠΈΠΏΠ΅ΡΠ³Π»ΠΈΠΊΠ΅ΠΌΠΈΠΈ III ΡΡΠ΅ΠΏΠ΅Π½ΠΈ ΡΠΎΠΊΡΠΈΡΠ½ΠΎΡΡΠΈ. ΠΠ΅ΠΆΠ΅Π»Π°ΡΠ΅Π»ΡΠ½ΡΡ
ΡΠ²Π»Π΅Π½ΠΈΠΉ IV ΡΡΠ΅ΠΏΠ΅Π½ΠΈ ΡΡΠΆΠ΅ΡΡΠΈ Π½Π΅ Π²ΡΡΠ²Π»Π΅Π½ΠΎ.ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. Π’Π΅ΡΠ°ΠΏΠΈΡ ΡΠ²Π΅ΡΠΎΠ»ΠΈΠΌΡΡΠΎΠΌ ΠΏΡΠΈΠ²Π΅Π»Π° ΠΊ 5-Π»Π΅ΡΠ½Π΅ΠΉ ΠΠ 16,2 % Ρ Π±ΠΎΠ»ΡΠ½ΡΡ
ΠΌΠ΅ΡΠ°ΡΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΠΌ ΠΏΠΎΡΠ΅ΡΠ½ΠΎ-ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΠΌ ΡΠ°ΠΊΠΎΠΌ, ΡΠ°Π½Π΅Π΅ ΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΡΡ
ΠΊ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ Π±Π΅Π²Π°ΡΠΈΠ·ΡΠΌΠ°Π±ΠΎΠΌ. ΠΠ»ΠΈΡΠ΅Π»ΡΠ½Π°Ρ ΡΠ΅ΡΠ°ΠΏΠΈΡ ΡΠ²Π΅ΡΠΎΠ»ΠΈΠΌΡΡΠΎΠΌ Π½Π΅ Π±ΡΠ»Π° Π°ΡΡΠΎΡΠΈΠΈΡΠΎΠ²Π°Π½Π° Ρ Π½ΠΎΠ²ΡΠΌΠΈ Π²ΠΈΠ΄Π°ΠΌΠΈ Π²ΡΡΠ°ΠΆΠ΅Π½Π½ΠΎΠΉ ΡΠΎΠΊΡΠΈΡΠ½ΠΎΡΡΠΈ ΠΈΠ»ΠΈ ΠΏΠΎΠ²ΡΡΠ΅Π½ΠΈΠ΅ΠΌ ΡΠ°ΡΡΠΎΡΡ Π½Π΅ΠΆΠ΅Π»Π°ΡΠ΅Π»ΡΠ½ΡΡ
ΡΠ²Π»Π΅Π½ΠΈΠΉ
Five-year overall survival of metastatic renal cell carcinoma patients treated with everolimus after progression on bevacizumab: a prospective multicenter study CRAD001LRU02T
Background. In a CRAD001LRU02T study of everolimus for metastatic renal cell carcinoma patients previously treated with bevacizumab Β±Β interferon, median overall survival (OS) was 17.4 months (95 % confidence interval 13.5β21.3 month).Objective of final analysis was to evaluate 5-year OS and long-term toxicity in this study.Materials and methods. Survival data were collected from 37 patients with bevacizumab-refractory metastatic renal cell carcinoma who received everolimus in a completed prospective multicenter study. Patients were predominantly male, 89 % had ECOG performance status of 0/1, 51 % received previous bevacizumab in combination with interferon, and 38/62% had MSKCC favorable/intermediate risk disease.Results. The 5-year survival rate was 16.2% (95 % confidence interval 14.1β18.3 %), with a median follow-up of 5 years. The 1-, and 3-year OS rates were 81.0 and 43.0 %, respectively. The median duration of second-line of everolimus was 315 (range 61β569) days. 11 (29.7 %) patients received third-line therapy with a median duration of 3.6 months. Confirmed objective tumor responses were seen in 5 (14.0 %) patients. 70.0 % (n = 26) patients had a stable disease. 1 (2.7 %) patient achieved complete response after 4 years of therapy. One (2.7 %) patientΒ discontinued everolimus therapy on their own accord due to relapse of systemic lupus erythematosus and one (2.7 %)Β patient had 14-days interruption of an everolimus therapy due to grade 3 hyperglycemia. No grade 4 treatment-related toxicity was found.Conclusions. Everolimus provided an estimated 5-year survival rate of 16.2 % for bevacizumab-resistant metastatic renal cell carcinoma. Prolonged everolimus was not associated with new types or increased severity of adverse events