Phase III BFORE Trial: Bosutinib Beats Imatinib for Frontline CML Treatment

Patients with previously untreated chronic myeloid leukemia (CML) who received bosutinib were more likely than those who received imatinib to respond to treatment and sustain their responses at two years, according to updated results from the phase III BFORE trial presented at the 2018 ASCO Annual Meeting.

Jorge E. Cortes, MD, from the University of Texas MD Anderson Cancer Center, presented one-year follow-up data at last year’s ASCO Annual Meeting, which provided the basis for bosutinib’s approval for the treatment of newly diagnosed, chronicphase (CP), Philadelphia chromosome– positive CML. At this year’s meeting, Dr. Cortes presented two-year follow-up data from BFORE, which “confirmed bosutinib’s superior efficacy over imatinib.”

In the multicenter, open-label, phase III BFORE trial, researchers enrolled 536 adult patients with untreated BCR-ABL1– positive, CP, Ph-positive or -negative CML. Participants were randomized 1:1 to receive either bosutinib 400 mg once-daily or imatinib 400 mg once-daily (n=268 for each arm). Median age in both groups was 53 years (range = 18-94 years), and 20 percent of each group had high-risk disease (per Sokal Index score).

After a median follow-up of 27 months (range not provided), the rates of major molecular response (MMR; primary endpoint) were higher in the bosutinibtreated group at 12 months and were maintained through 18- and 24-month timepoints in the entire intent-to-treat (ITT) population (see TABLE).

Response Rates in the ITT Population

At two years, 61 percent of bosutinibtreated patients and 51 percent of imatinib treated patients remained in MMR, which translated to 37-percent higher odds of experiencing MMR at 24 months (hazard ratio [HR] = 1.37; 95% CI 1.11-1.68; p<0.001). “MMR responses occurred early, and the differences were maintained, with no evidence of the gaps [between the two treatment arms] closing,” Dr. Cortes reported.

These differences also were observed in the modified ITT (mITT) population, which included 246 bosutinib-treated and 241 imatinib-treated patients with typical BCR-ABL1 transcript types (e13a2 and/or e14a2). Sixty-two percent and 53 percent, respectively, were in MMR at two years (p=0.05).

Rates of complete cytogenetic response were higher among bosutinib-treated patients (82% vs. 76%; HR=1.34; 95% CI 1.10-1.63; p=0.005), as were rates of deep molecular response, though the differences were smaller at two years than one year (see TABLE). “Deeper responses [like molecular response at 4- or 4.5-log reduction, or MR4 and MR4.5] have become an important focus for treatment consideration,” Dr. Cortes noted, adding that, “even though it’s early, we still see a benefit with bosutinib over imatinib [for this endpoint].”

A total of 13 patients had disease that transformed to accelerated- or blast-phase CML: six (2.2%) in the bosutinib arm and seven (2.6%) in the imatinib arm. “Of all transformations, six (three in each arm) were transient and early, occurring within two weeks,” Dr. Cortes noted, adding that “these do not represent what we consider a true transformation.” All of these patients continued on study drug or discontinued treatment for reasons other than disease progression or death.

The safety profile was “as anticipated,” Dr. Cortes added. The incidence of grade ≥3 myelosuppression were similar in both bosutinib and imatinib arms (49 [18%] and 59 [22%], respectively). Diarrhea and elevated liver function were more frequent in bosutinib-treated patients, but were manageable, early, and improved over time with treatment interruptions, the researchers noted.

While Dr. Cortes concluded that bosutinib is a “valuable” option for frontline treatment of CML, the BFORE trial was not powered to evaluate survival.

The authors report financial relationships with Pfizer and Novartis, the developers of bosutinib and imatinib, respectively.


Cortes JE, Mauro MJ, Deininger MWN, et al. Bosutinib vs imatinib for newly diagnosed chronic myeloid leukemia in the BFORE trial: 24-month follow-up. Abstract #7002. Presented at the 2018 ASCO Annual Meeting, June 2, 2018; Chicago, IL.