Bosutinib (BOS) versus imatinib (IM) for newly diagnosed chronic myeloid leukemia (CML): Initial results from the BFORE trial.

Abstract

7002 Background: BOS is a potent, dual SRC/ABL tyrosine kinase inhibitor approved for treatment (tx) of adults with Ph+ CML resistant/intolerant to prior therapy. We assessed the efficacy and safety of BOS vs IM for first-line tx of chronic phase (CP) CML. Methods: In this ongoing, multinational, phase 3, open-label study, 536 patients (pts) with newly diagnosed CP CML were randomized 1:1 to BOS 400 mg QD (n = 268) or IM 400 mg QD (n = 268 [3 not treated]). Per protocol, efficacy was assessed in a modified intent-to-treat (ITT) population of 487 Ph+ pts (BOS, n = 246; IM, n = 241) with e13a2/e14a2 transcripts; results in full ITT will also be presented. Results: After≥12 mo of follow-up, 78% of BOS and 73.2% of IM pts remain on tx with median tx durations of 14.1 and 13.8 mo, respectively. Major molecular response (MMR) rate at 12 mo (primary endpoint) was significantly higher with BOS vs IM (47.2% vs 36.9%; P= 0.02). Time to MMR was shorter for BOS (hazard ratio [HR] 1.34; P< 0.02). Rate of complete cytogenetic response (CCyR) by 12 mo was also significantly higher with BOS vs IM (77.2% vs 66.4%; P< 0.008), with time to CCyR shorter for BOS (HR 1.38; P≤0.001). Rates of BCR-ABL transcripts≤10% (Intl Scale) at 3 mo (75.2% vs 57.3%), MR4 at 12 mo (20.7% vs 12%) and MR4.5 at 12 mo (8.1% vs 3.3%) were higher with BOS vs IM, respectively (all P< 0.025). 1 BOS pt and 4 IM pts discontinued tx due to progression to accelerated or blast phase. There were no deaths within 28 d of last dose of BOS and 4 with IM. Safety data were consistent with known safety profiles of BOS and IM. 12.7% of BOS and 8.7% of IM pts discontinued due to drug-related toxicity. Gr≥3 diarrhea (7.8% vs 0.8%) and increased alanine (19% vs 1.5%) and aspartate (9.7% vs 1.9%) aminotransferase levels were more common with BOS. Cardio-, peripheral- and cerebrovascular events were infrequent (3%, 1.5% and 0% BOS vs 0.4%, 1.1% and 0.4% IM; gr≥3: 1.5%, 0% and 0% vs 0%, 0% and 0.4%). Conclusions: Pts on BOS had significantly higher rates of 12-mo MMR and CCyR and achieved responses faster than those on IM, but had higher incidence of gastrointestinal events and transaminase elevations. Results suggest BOS may be an important tx option for pts with newly diagnosed CP CML. Funding. Avillion, Pfizer. Clinical trial information: NCT02130557 .