Bosutinib Distinguishes Itself as Potential Option for Newly-Diagnosed CML

Michael J. Mauro, MD

Initial results from a phase III trial indicated that patients with newly diagnosed chronic myeloid leukemia (CML) treated with bosutinib (Bosulif) achieved response faster than patients treated with imatinib (Gleevec).

Data from the randomized, multinational BFORE trial presented at the 2017 Annual SOHO Meeting showed that bosutinib, a dual SCR/ABL tyrosine kinase inhibitor (TKI), induced significantly higher rates of 12-month major molecular response and complete cytogenetic response in this patient population.

Major molecular response rate was significantly higher in patients treated with bosutinib compared with those treated with imatinib (47.2% vs 36.9%; P= .02). Major molecular response rate in the intent-to-treat population was higher with bosutinib (47.2% vs 36.9%; odds ratio [OR], 1.55;P= .02). By 12 months, complete cytogenetic response rate was significantly higher with bosutinib (77.2% vs 66.4%; OR, 1.74;P<.01) in this cohort.

Survival was 99.6% (95% CI, 0.97-0.999) for bosutinib comapred with 97.9% (95% CI, 0.95-0.991) for patients treated with imatinib.

Additionally, time to major molecular response rate was shorter with bosutinib (HR, 1.34;P<.02).

Michael J. Mauro, MD, hematologist and leader of the Myeloproliferative Neoplasms Program at Memorial Sloan Kettering Cancer Center, presented the safety and efficacy data. He noted that the TKI was associated with a higher incidence of gastrointestinal events, but a lower incidence of musculoskeletal events.

&ldquo;Bosutinib could become a new frontline treatment option in CML,&rdquo; he said. &ldquo;Responses occurred earlier with bosutinib [and] safety data were consistent with known profiles.&rdquo;

In the study, 536 patients with newly diagnosed chronic-phase (CP) CML were randomly assigned to bosutinib (n = 268) or imatinib (n = 265) at 400mg once daily. The bosutinib dose was lowered from the initial 500 mg daily dose in hopes of reducing toxicity.

All-grade diarrhea was significantly higher with bosutinib (70% vs 34%). Patients in the experimental arm were also more likely to experience all-grade liver toxicity (40% vs 14%).

Although response rates are high with bosutinib, progression remains a question, said Mauro.

"I think we need to continue to look at the safety and the long-term follow-up and see if this will fit into our treatment," he said.

Based on data from the BFORE trial, the FDA in August granted bosutinib priority review to a supplemental new drug application (sNDA) for the first-line treatment of adult patients with Philadelphia chromosome-positive (Ph+) CML. The drug is currently indicated in the United States for adult patients with Ph+ CML who are resistant or intolerant to prior therapy.

Pfizer and Avillion, the co-developers of bosutinib, also announcd that the European Medicines Agency is also reviewing an application for the use of the drug in the same patient population.

Reference:

Cortes J, Gambacorti-Passerini C, Deininger M, et al. Bosutinib (BOS) vs Imatinib (IM) for Newly Diagnosed Chronic Myeloid Leukemia (CML): Initial Results from the BFORE Trial. Presented at: 2017 SOHO Annual Meeting; Houston, TX; September 13-16, 2017.