Long-term later-line bosutinib benefits CML patients
medwireNews: Bosutinib elicits durable responses in chronic phase–chronic myeloid leukaemia (CML) patients who have failed prior treatment with multiple tyrosine kinase inhibitors (TKIs), shows an updated analysis of an ongoing phase I/II trial.
The analysis included 119 patients given the dual Src/Abl TKI after developing resistance or intolerance to not only imatinib but also dasatinib and/or nilotinib. Participants were treated for a median of 8.6 months and followed up for a median of 32.7 months.
At 4 years, 74% of 117 evaluable patients attained or maintained a confirmed complete haematological response (cCHR), while 40% and 32% of 112 attained or maintained a major cytogenetic response (MCyR) or complete cytogenetic response (CCyR), respectively.
Jorge Cortes (University of Texas MD Anderson Cancer Center, Houston, USA) and co-authors estimate that the likelihood of responders maintaining a CHR, MCyR and CCyR at 4 years is 63%, 69% and 54%, respectively.
As reported in the American Journal of Hematology, the 4-year cumulative incidence of on-treatment progression, including transformation to accelerated or blast phase, and death was 24%. And the estimated 4-year overall survival rate was 78%.
The researchers also investigated predictors of long-term outcomes, and found that increased basophil levels at baseline were associated with a shorter progression-free survival, while no response to prior treatment with dasatinib or nilotinib predicted shorter overall survival.
They identified several parameters associated with either MCyR, CCyR or both – for instance, positivity for the Philadelphia chromosome in 35% of cells or fewer compared with in 95% of cells or more significantly predicted MyCR and CCyR at all timepoints during treatment.
However, the study authors urge caution in interpreting these results as they did not adjust for confounding factors.
The adverse event profile of bosutinib was similar to that observed in previous studies, they remark. Thrombocytopenia (26%), neutropenia (16%), diarrhoea (9%) and anaemia (7%) were the most frequent treatment-emergent side effects of grade 3 or 4 in this updated analysis.
With the exception of elevated blood creatinine and pleural effusion, new incidences of which were higher in year 4 than in previous years, “newly occurring [adverse events] generally decreased in frequency after the first year of treatment”, Cortes et al write.
And they conclude: “Overall, 4 years after last enrollment, bosutinib continues to demonstrate durable efficacy and manageable toxicity for the majority of patients with [chronic phase] CML resistant or intolerant to multiple prior TKIs who are able to remain on treatment after the first year, representing an important treatment option for patients in this setting.”
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