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BACKGROUND/AIMS: An open-label, multi-center, expanded access study was conducted in patients with advanced neuroendocrine tumors (NET) treated with everolimus (10 mg/day) to assess safety and health-related quality of life (HRQOL). METHODS: Of the 246 patients enrolled, 126 have pancreatic NET (pNET) and 120 have non-pNET. Patients continued treatment until disease progression, unacceptable toxicity, death, until commercial availability of everolimus, or May 2012, whichever came first. Adverse events (AEs) were analyzed according to Common Terminology Criteria version 4.0. HRQOL was assessed at baseline, for three 28-day cycles, and then at every three cycles until end of treatment (EOT) with EQ-5D, EORTC QLQ-C30, and EORTC QLQ-GINET21 instruments. RESULTS: The most common grade 3 or 4 AEs included hyperglycemia, infections, stomatitis, fatigue, and abdominal pain. In patients with pNET, mean (± SD) EQ VAS score remained stable at EOT (baseline, 68.8 ± 19.9 vs. EOT, 66.5 ± 20.6) without clinically significant change in QLQ-C30 global health status (change from baseline, - 3.9; n = 86). For patients with non-pNET, a reduction in EQ VAS score (63.9 ± 19.0 vs. 55.3 ± 23.0) with clinically significant changes in QLQ-C30 global health status (-13.0; n = 69) was seen by EOT. EQ-5D utility scores remained stable in patients with pNET and a moderate decrease was reported by patients with non-pNET. CONCLUSIONS: The safety profile of everolimus was consistent with the previous studies without adversely affecting HRQOL in pNET. Lower baseline HRQOL scores and more frequent comorbidities might have contributed to the worse outcomes in non-pNET. TRIAL REGISTRATION: EudraCT no. 2010-023032-17.

BACKGROUND: Hyperglycemia and hypercholesterolemia are class effects of mammalian target of rapamycin inhibitors. The purpose of this study was to characterize safety and efficacy of patients with metastatic renal cell carcinoma (mRCC) treated with everolimus in RECORD-1 (REnal Cell cancer treatment with Oral RAD001 given Daily) and REACT (RAD001 Expanded Access Clinical Trial in RCC) who developed these events. PATIENTS AND METHODS: Adults with vascular endothelial growth factor-refractory mRCC received everolimus 10 mg/d in the randomized RECORD-1 (n = 277) and open-label REACT (n = 1367) studies. Outcomes included safety, treatment duration, overall response, and progression-free survival for patients who developed hypercholesterolemia or hyperglycemia. RESULTS: In RECORD-1, 12% (33 of 277) and 20% (55 of 277) of patients developed any grade hyperglycemia or hypercholesterolemia, respectively, with only 6% (78 of 1367) and 1% (14 of 1367) of the same events, respectively, in REACT. Median everolimus treatment duration was similar for patients with hyperglycemia or hypercholesterolemia (RECORD-1, 6.2 and 6.2 months, respectively; REACT, 4.4 and 4.5 months, respectively), but longer than the overall populations (RECORD-1, 4.6 months; REACT, 3.2 months). In RECORD-1/REACT, 82%/68% of patients with hyperglycemia and 75%/71% of patients with hypercholesterolemia achieved partial response or stable disease. The incidence of clinically notable Grade 3 or 4 adverse events, other than anemia and lymphopenia, appeared to be similar across trials and subgroups. Although there was a trend for improved progression-free survival with development of hyperglycemia or hypercholesterolemia, the association was not statistically significant. CONCLUSION: Hyperglycemia and hypercholesterolemia were observed in low numbers of patients, and although these events might be associated with improved response to everolimus, the differences were not significant. These findings should be vali

BACKGROUND/AIMS: An open-label, multi-center, expanded access study was conducted in patients with advanced neuroendocrine tumors (NET) treated with everolimus (10 mg/day) to assess safety and health-related quality of life (HRQOL). METHODS: Of the 246 patients enrolled, 126 have pancreatic NET (pNET) and 120 have non-pNET. Patients continued treatment until disease progression, unacceptable toxicity, death, until commercial availability of everolimus, or May 2012, whichever came first. Adverse events (AEs) were analyzed according to Common Terminology Criteria version 4.0. HRQOL was assessed at baseline, for three 28-day cycles, and then at every three cycles until end of treatment (EOT) with EQ-5D, EORTC QLQ-C30, and EORTC QLQ-GINET21 instruments. RESULTS: The most common grade 3 or 4 AEs included hyperglycemia, infections, stomatitis, fatigue, and abdominal pain. In patients with pNET, mean (± SD) EQ VAS score remained stable at EOT (baseline, 68.8 ± 19.9 vs. EOT, 66.5 ± 20.6) without clinically significant change in QLQ-C30 global health status (change from baseline, - 3.9; n = 86). For patients with non-pNET, a reduction in EQ VAS score (63.9 ± 19.0 vs. 55.3 ± 23.0) with clinically significant changes in QLQ-C30 global health status (-13.0; n = 69) was seen by EOT. EQ-5D utility scores remained stable in patients with pNET and a moderate decrease was reported by patients with non-pNET. CONCLUSIONS: The safety profile of everolimus was consistent with the previous studies without adversely affecting HRQOL in pNET. Lower baseline HRQOL scores and more frequent comorbidities might have contributed to the worse outcomes in non-pNET. TRIAL REGISTRATION: EudraCT no. 2010-023032-17.

The present exploratory analysis examined the efficacy, safety, and quality-of-life effects of everolimus (EVE) + exemestane (EXE) in the subgroup of patients in BOLERO-2 whose last treatment before study entry was in the (neo)adjuvant setting. In BOLERO-2, patients with hormone-receptor-positive (HR(+)), human epidermal growth factor receptor-2-negative (HER2(-)) advanced breast cancer recurring/progressing after a nonsteroidal aromatase inhibitor (NSAI) were randomly assigned (2:1) to receive EVE (10 mg/day) + EXE (25 mg/day) or placebo (PBO) + EXE. The primary endpoint was progression-free survival (PFS) by local assessment. Overall, 137 patients received first-line EVE + EXE (n = 100) or PBO + EXE (n = 37). Median PFS by local investigator assessment nearly tripled to 11.5 months with EVE + EXE from 4.1 months with PBO + EXE (hazard ratio = 0.39; 95 % CI 0.25-0.62), while maintaining quality of life. This was confirmed by central assessment (15.2 vs 4.2 months; hazard ratio = 0.32; 95 % CI 0.18-0.57). The marked PFS improvement in patients receiving EVE + EXE as first-line therapy for disease recurrence during or after (neo)adjuvant NSAI therapy supports the efficacy of this combination in the first-line setting. Furthermore, the results highlight the potential benefit of early introduction of EVE + EXE in the management of HR(+), HER2(-) advanced breast cancer in postmenopausal patients.

The present exploratory analysis examined the efficacy, safety, and quality-of-life effects of everolimus (EVE) + exemestane (EXE) in the subgroup of patients in BOLERO-2 whose last treatment before study entry was in the (neo)adjuvant setting. In BOLERO-2, patients with hormone-receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2 -) advanced breast cancer recurring/progressing after a nonsteroidal aromatase inhibitor (NSAI) were randomly assigned (2:1) to receive EVE (10 mg/day) + EXE (25 mg/day) or placebo (PBO) + EXE. The primary endpoint was progression-free survival (PFS) by local assessment. Overall, 137 patients received first-line EVE + EXE (n = 100) or PBO + EXE (n = 37). Median PFS by local investigator assessment nearly tripled to 11.5 months with EVE + EXE from 4.1 months with PBO + EXE (hazard ratio = 0.39; 95 % CI 0.25-0.62), while maintaining quality of life. This was confirmed by central assessment (15.2 vs 4.2 months; hazard ratio = 0.32; 95 % CI 0.18-0.57). The marked PFS improvement in patients receiving EVE + EXE as first-line therapy for disease recurrence during or after (neo)adjuvant NSAI therapy supports the efficacy of this combination in the first-line setting. Furthermore, the results highlight the potential benefit of early introduction of EVE + EXE in the management of HR+, HER2- advanced breast cancer in postmenopausal patients. © 2013 The Author(s)., SCOPUS: ar.j, info:eu-repo/semantics/published

The present exploratory analysis examined the efficacy, safety, and quality-of-life effects of everolimus (EVE) + exemestane (EXE) in the subgroup of patients in BOLERO-2 whose last treatment before study entry was in the (neo)adjuvant setting. In BOLERO-2, patients with hormone-receptor-positive (HR(+)), human epidermal growth factor receptor-2-negative (HER2(-)) advanced breast cancer recurring/progressing after a nonsteroidal aromatase inhibitor (NSAI) were randomly assigned (2:1) to receive EVE (10 mg/day) + EXE (25 mg/day) or placebo (PBO) + EXE. The primary endpoint was progression-free survival (PFS) by local assessment. Overall, 137 patients received first-line EVE + EXE (n = 100) or PBO + EXE (n = 37). Median PFS by local investigator assessment nearly tripled to 11.5 months with EVE + EXE from 4.1 months with PBO + EXE (hazard ratio = 0.39; 95 % CI 0.25-0.62), while maintaining quality of life. This was confirmed by central assessment (15.2 vs 4.2 months; hazard ratio = 0.32; 95 % CI 0.18-0.57). The marked PFS improvement in patients receiving EVE + EXE as first-line therapy for disease recurrence during or after (neo)adjuvant NSAI therapy supports the efficacy of this combination in the first-line setting. Furthermore, the results highlight the potential benefit of early introduction of EVE + EXE in the management of HR(+), HER2(-) advanced breast cancer in postmenopausal patients.

The present exploratory analysis examined the efficacy, safety, and quality-of-life effects of everolimus (EVE) + exemestane (EXE) in the subgroup of patients in BOLERO-2 whose last treatment before study entry was in the (neo)adjuvant setting. In BOLERO-2, patients with hormone-receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2 -) advanced breast cancer recurring/progressing after a nonsteroidal aromatase inhibitor (NSAI) were randomly assigned (2:1) to receive EVE (10 mg/day) + EXE (25 mg/day) or placebo (PBO) + EXE. The primary endpoint was progression-free survival (PFS) by local assessment. Overall, 137 patients received first-line EVE + EXE (n = 100) or PBO + EXE (n = 37). Median PFS by local investigator assessment nearly tripled to 11.5 months with EVE + EXE from 4.1 months with PBO + EXE (hazard ratio = 0.39; 95 % CI 0.25-0.62), while maintaining quality of life. This was confirmed by central assessment (15.2 vs 4.2 months; hazard ratio = 0.32; 95 % CI 0.18-0.57). The marked PFS improvement in patients receiving EVE + EXE as first-line therapy for disease recurrence during or after (neo)adjuvant NSAI therapy supports the efficacy of this combination in the first-line setting. Furthermore, the results highlight the potential benefit of early introduction of EVE + EXE in the management of HR+, HER2- advanced breast cancer in postmenopausal patients. © 2013 The Author(s)., SCOPUS: ar.j, info:eu-repo/semantics/published