Combo worsens platelet recovery in MDS
Results from the phase 3 SUPPORT trial suggest there is no role for the combination of eltrombopag and azacitidine in patients with intermediate- or high-risk myelodysplastic syndromes (MDS), according to investigators.
Adding eltrombopag to azacitidine worsened platelet recovery, reduced the overall response rate, and did not improve overall or progression-free survival when compared to azacitidine plus placebo.
Investigators had hypothesized that eltrombopag would reduce the thrombocytopenia exacerbated by azacitidine treatment.
Not only was this not the case, but the investigators observed a trend toward increased progression to acute myeloid leukemia (AML) in eltrombopag-treated patients.
An independent monitoring committee recommended the trial be terminated early.
Michael Dickinson, MBBS, of Peter MacCallum Cancer Centre and Royal Melbourne Hospital in Melbourne, Australia, and his colleagues reported results from the trial in Blood.
The investigators conducted the SUPPORT study (NCT02158936) to investigate the efficacy and safety of eltrombopag as platelet supportive care in patients with intermediate- to high-risk MDS and thrombocytopenia who were receiving azacitidine.
Study design
Investigators randomized patients 1:1 to eltrombopag or placebo in combination with azacitidine. Patients had to have at least one platelet count less than 75 x 109/L within 28 days prior to the first azacitidine dose.
Patients received azacitidine subcutaneously at a dose of 75 mg/m2 once daily on 7 consecutive days for 28 days.
Patients received eltrombopag or placebo at a starting dose of 200 mg/day (100 mg/day for East Asians), adjusted by 100 mg increments (50 mg increments for East Asians) to a maximum of 300 mg/day (150 mg/day for East Asians).
Patient disposition
Investigators enrolled 356 patients from 30 countries between June 2014 and December 2015, randomizing 179 patients to eltrombopag and 177 to placebo.
Patients were a median age of 70, 66% were male, 83% were white, and 47% had platelet counts between 20 and 50 x 109/L.
At the start of the trial, 19% of patients (n=66) were platelet transfusion-dependent—16% (29/179) in the eltrombopag group and 21% (37/177) in the placebo group.
Treatment exposure
Patients received eltrombopag for a median of 83 days (range, 60 to 148) and placebo for a median of 149 days (range, 8 to 503).
For non-East Asian patients, the mean dose of eltrombopag was 205 mg/day (range, 65 to 293), and the mean dose of placebo was 245 mg/day (range, 107 to 316).
Sixty-eight patients (38%) in the eltrombopag arm received the recommended number of six or more azacitidine cycles, compared to 91 (51%) in the placebo arm.
Two patients in the eltrombopag arm did not receive treatment. Therefore, the safety analyses were conducted on the 177 treated patients in each arm.
Safety
The most common reason for treatment discontinuation was termination of the study. Thirty-two percent of patients in the eltrombopag cohort and 44% in the placebo cohort discontinued for this reason.
Patients had to discontinue eltrombopag or placebo if azacitidine was discontinued, and this occurred in 30% of patients in the eltrombopag group and 26% in the placebo group.
Twenty-two percent of eltrombopag-treated patients discontinued due to adverse events (AEs), compared with 14% in the placebo group.
The most common reasons for azacitidine discontinuation in the eltrombopag and placebo arms, respectively, were study termination (35% and 46%), AEs (25% and 19%), disease progression (15% and 14%), and patient decision (11% and 9%).
AEs with the greatest difference between the eltrombopag and placebo arms, respectively, were febrile neutropenia (31% and 21%), neutropenia (31% and 26%), nausea (31% and 26%), and diarrhea (25% and 14%).
