Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 52269-52280 |
| Number of pages | 12 |
| Journal | Oncotarget |
| Volume | 8 |
| Issue number | 32 |
| DOIs | |
| Publication status | Published - 2017 |
Cite this
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The mTOR inhibitor everolimus in combination with azacitidine in patients with relapsed/refractory acute myeloid leukemia : a phase Ib/II study. / Tan, Peter; Tiong, Ing Soo; Fleming, Shaun; Pomilio, Giovanna; Cummings, Nik; Droogleever, Mark; McManus, Julie; Schwarer, Anthony; Catalano, John; Patil, Sushrut; Avery, Sharon; Spencer, Andrew; Wei, Andrew.
In: Oncotarget, Vol. 8, No. 32, 2017, p. 52269-52280.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - The mTOR inhibitor everolimus in combination with azacitidine in patients with relapsed/refractory acute myeloid leukemia
T2 - a phase Ib/II study
AU - Tan, Peter
AU - Tiong, Ing Soo
AU - Fleming, Shaun
AU - Pomilio, Giovanna
AU - Cummings, Nik
AU - Droogleever, Mark
AU - McManus, Julie
AU - Schwarer, Anthony
AU - Catalano, John
AU - Patil, Sushrut
AU - Avery, Sharon
AU - Spencer, Andrew
AU - Wei, Andrew
PY - 2017
Y1 - 2017
N2 - Therapeutic options are limited in relapsed/refractory acute myeloid leukemia (AML). We evaluated the maximum tolerated dose (MTD) and preliminary efficacy of mammalian target of rapamycin (mTOR) inhibitor, everolimus (days 5–21) in combination with azacitidine 75 mg/m2 subcutaneously (days 1–5 and 8–9 every 28 days) in 40 patients with relapsed (n = 27), primary refractory (n = 11) or elderly patients unfit for intensive chemotherapy (n = 2). MTD was not reached following everolimus dose escalation (2.5, 5 or 10 mg; n = 19) to the 10 mg dose level which was expanded (n = 21). Major adverse events (grade > 2) were mostly disease-related: neutropenia (73%), thrombocytopenia (67%), mucositis (24%) and febrile neutropenia (19%). Overall survival (OS) of the entire cohort was 8.5 months, and overall response rate (ORR; including CR/CRi/PR/MLFS) was 22.5%. Furthermore, a landmark analysis beyond cycle 1 revealed superior OS and ORR in patients receiving 2.5 mg everolimus with azoles, compared to those without azoles (median OS 12.8 vs. 6.0 months, P = 0.049, and ORR 50% vs. 16%, P = 0.056), potentially due to achievement of higher everolimus blood levels. This study demonstrates that everolimus in combination with azacitidine is tolerable, with promising clinical activity in advanced AML.
AB - Therapeutic options are limited in relapsed/refractory acute myeloid leukemia (AML). We evaluated the maximum tolerated dose (MTD) and preliminary efficacy of mammalian target of rapamycin (mTOR) inhibitor, everolimus (days 5–21) in combination with azacitidine 75 mg/m2 subcutaneously (days 1–5 and 8–9 every 28 days) in 40 patients with relapsed (n = 27), primary refractory (n = 11) or elderly patients unfit for intensive chemotherapy (n = 2). MTD was not reached following everolimus dose escalation (2.5, 5 or 10 mg; n = 19) to the 10 mg dose level which was expanded (n = 21). Major adverse events (grade > 2) were mostly disease-related: neutropenia (73%), thrombocytopenia (67%), mucositis (24%) and febrile neutropenia (19%). Overall survival (OS) of the entire cohort was 8.5 months, and overall response rate (ORR; including CR/CRi/PR/MLFS) was 22.5%. Furthermore, a landmark analysis beyond cycle 1 revealed superior OS and ORR in patients receiving 2.5 mg everolimus with azoles, compared to those without azoles (median OS 12.8 vs. 6.0 months, P = 0.049, and ORR 50% vs. 16%, P = 0.056), potentially due to achievement of higher everolimus blood levels. This study demonstrates that everolimus in combination with azacitidine is tolerable, with promising clinical activity in advanced AML.
U2 - 10.18632/oncotarget.13699
DO - 10.18632/oncotarget.13699
M3 - Article
VL - 8
SP - 52269
EP - 52280
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 32
ER -