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

Authors

null

Tim H. Brummendorf

Universitätsklinikum Aachen, Universitätsklinikum Hamburg-Eppendorf, Aachen & Hamburg, Germany

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

Organizations

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

Research Funding

Pharmaceutical/Biotech Company
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.

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Abstract Details

Meeting

2012 ASCO Annual Meeting

Session Type

Poster Discussion Session

Session Title

Leukemia, Myelodysplasia, and Transplantation

Track

Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant

Sub Track

Leukemia

Clinical Trial Registration Number

NCT00261846

Citation

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

DOI

10.1200/jco.2012.30.15_suppl.6511

Abstract #

6511

Poster Bd #

3

Abstract Disclosures

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