Early switch to dasatinib offers clinical benefit to CML patients

Patients were followed for a median of 30 months.

Of the randomized patients—the intent-to-treat (ITT) population—143 (84%) in the dasatinib arm and 72 (84%) in the imatinib arm continued on treatment.

Study drug toxicity was the most common reason for discontinuing treatment and occurred in 9 patients (5%) in the dasatinib arm and 3 (4%) in the imatinib arm.

Nearly half the imatinib patients (n=42, 49%) crossed over to dasatinib at a median of 9 months.

The median duration of treatment was 22 months (range, 1 – 44) for patients on imatinib who did not cross over and 15 months (range, <1 – 38) for patients on dasatinib after crossing over from imatinib.

Response

In the ITT population, the rate of MMR at 12 months was 29% in the dasatinib arm and 13% in the imatinib arm (P=0.005).

The median time to MMR was significantly shorter for patients who received dasatinib compared with imatinib—14 months and 20 months, respectively (P=0.053).

“Over 60% of patients on the dasatinib arm achieved a major molecular response,” Dr. Cortes said. “This compares to about 55% of patients on the imatinib arm, even when you consider the crossover of a significant number of these patients.”

A few patients achieved a molecular response of a 4.5-log reduction in BCR-ABL1 transcripts (MR4.5).

“Of course, the follow-up is short, but we had twice as many patients [on dasatinib] at 12 months with MR4.5— 5% with dasatinib versus 2% with imatinib,” Dr. Cortes said.

Survival outcomes

Both overall and progression-free survival “look very good with both treatment approaches,” Dr. Cortes pointed out.

At a median follow-up of 30 months, the overall survival in the ITT population was 98.8% in each treatment arm.

Progression-free survival was 96.9% in the dasatinib arm and 97.6% in the imatinib arm.

“It is important to note that no patient in either treatment arm has transformed to accelerated or blast phase,” Dr. Cortes said.

Safety

Treatment was well tolerated with both agents, Dr. Cortes observed, with very few grade 3 adverse events (AEs) noted to date.

“The one that stands out here, and it’s only 2% of patients, is headache with dasatinib,” he said.

The headache did not lead to treatment discontinuation, and the patients were managed with dose adjustments.

The investigators observed no new safety signals with either drug.

Treatment-emergent AEs of any grade occurring in 15% or fewer dasatinib- or imatinib-treated patients, respectively, in the ITT population included headache (15%, 9%), diarrhea (9%, 8%), nausea (9%, 8%), eyelid edema (1%, 9%), hypocalcemia (1%, 7%), and muscle spasms (1%, 8%).

Patients who crossed over to dasatinib had similar rates of AEs to those documented for imatinib.

“They are typical for what we know of both of these tyrosine kinase inhibitors,” Dr. Cortes stated.

Investigators observed pleural effusion in 9 (5%) patients on dasatinib, and only one grade 3. That patient discontinued therapy due to the AE.

Of the patients who were on imatinib and crossed over to dasatinib, 3 (7%) experienced pleural effusion, most of them grade 1 or 2. One patient with grade 4 discontinued therapy with dasatinib due to the AE.

“Hematologic toxicity has been mild,” Dr. Cortes said, and in keeping with the known toxicities of dasatinib and imatinib.

Grade 3/4 treatment-emergent AEs in the dasatinib and imatinib arms, respectively, in the ITT population included anemia (5%, 4%), neutropenia (11%, 16%), thrombocytopenia (11%, 11%), and leukopenia (1%, 1%).

Patients who crossed over to dasatinib experienced more of these AEs than patients who did not cross over, Dr. Cortes clarified, but they are still within the expected range with these agents.