100244-114

Efficacy and safety of bosutinib (BOS) for Philadelphia chromosome–positive (Ph+) leukemia in older versus younger patients (pts).

Subcategory: 
Category: 
Leukemia Myelodysplasia and Transplantation
Session Type and Session Title: 
Poster Discussion Session, Leukemia, Myelodysplasia, and Transplantation
Abstract Number: 

6511

Citation: 

J Clin Oncol 30, 2012 (suppl; abstr 6511)

Author(s): 

Tim H. Brummendorf, Carlo Gambacorti-Passerini, Philippe Schafhausen, Hanna Jean Khoury, Andreas Hochhaus, Thomas Kindler, Thomas Fischer, Nadine Besson, Eric Leip, Virginia Kelly, Jorge E. Cortes; Universitätsklinikum Aachen, Universitätsklinikum Hamburg-Eppendorf, Aachen & Hamburg, Germany; University of Milan-Bicocca, Monza, Italy; Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany; Emory University School of Medicine, Atlanta, GA; Universitätsklinikum Jena, Jena, Germany; Johannes Gutenberg-Universität, Mainz, Germany; Universitätsklinikum Magdeburg, Magdeburg, Germany; Pfizer Global Research and Development, Paris, France; Pfizer Inc., Cambridge, MA; University of Texas M. D. Anderson Cancer Center, Houston, TX


Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures

Abstract: 

Background: BOS is an oral dual Src/Abl kinase inhibitor with potent activity in Ph+ leukemia. Methods: Efficacy and safety of BOS 500 mg/d was evaluated in older (≥65 y; n = 119) and younger (<65 y; n = 451) pts in 3 cohorts: chronic phase chronic myeloid leukemia (CP CML) after imatinib (IM; CP2L cohort; n = 287); CP CML after IM + dasatinib (DAS) and/or nilotinib (NIL; CP3L cohort; n = 119); and accelerated/blast phase (AP/BP) CML or acute lymphoblastic leukemia after IM ± DAS and/or NIL (ADV cohort; n = 164). Results: Baseline events (≥65 y vs <65 y) included respiratory disorders (35% vs 13%), cardiac disorders (29% vs 9%), and diabetes (4% vs 4%). Median baseline medications were 3 (≥65 y) and 5 (<65 y). Median BOS duration was 11 mo and median follow-up was 31 mo for all pts. 80% of ³65 y and 67% of <65 y pts discontinued BOS, including 32% and 18% due to an adverse event (AE; most commonly thrombocytopenia [6% vs 3%]). Rates of response were similar or lower in older versus younger pts (Table). On-treatment transformation to AP/BP CML was similar between groups. Incidences of nonhematologic treatment-emergent AEs were generally similar between older and younger pts, notably (all grades/grade ≥3 for ≥65 y vs <65 y): diarrhea (85%/9% vs 81%/8%), infection (56%/15% vs 49%/10%), and edema (8%/0% vs 4%/<1%). Common grade ≥3 lab abnormalities (≥65 y vs <65 y) were thrombocytopenia (35% vs 35%), neutropenia (21% vs 25%), and anemia (19% vs 19%). Conclusions: BOS demonstrated similar efficacy and acceptable safety in both older and younger pts across Ph+ leukemia cohorts.
CP2L
CP3L
ADV
≥65 y <65 y ≥65 y <65 y ≥65 y <65 y
na 63 223 25 92 29 122
MHR - - - - 28% 30%
CHR 81% 87% 72% 74% 14% 25%
2-y probability of maintaining CHRb 67% 75% 65% 69% 75% 54%
na 61 204 22 88 26 116
MCyR 43% 57% 27% 34% 23% 32%
CCyR 38% 45% 23% 24% 19% 22%
2-y probability of maintaining MCyRb 73% 74% 83% 56% 20% 31%
n 63 224 26 93 30 134
Transformation to AP/BP 3% 5% 4% 4% 4% 3%
2-y probability of survivalb 87% 92% 80% 85% 43% 46%

Abbreviations: MHR, major hematologic response; CHR, complete hematologic response; MCyR, major cytogenetic response; CCyR, complete cytogenetic response.

aEvaluable pts had received ≥1 dose of BOS and a valid baseline assessment.

bKaplan-Meier estimate.