Tipifarnib Is Well Tolerated as Maintenance Therapy In Acute Myeloid Leukemia (AML). Significant, but Non-Fatal, Hematologic Toxicity Not Ameliorated by Dose Reduction. Preliminary Results of the Phase III Intergroup Trial E2902

Abstract 3315 The Eastern Cooperative Oncology Group (ECOG) trial, E2902, was a randomized phase III intergroup trial of the Farnesyl Transferase Inhibitor, R115777(Tipifarnib), as maintenance therapy for acute myeloid leukemia (AML). Patients (pts) with AML in remission after requiring salvage therapy (primary induction failure or second or subsequent remission) or over the age of 60 in first remission were eligible. A confirmatory bone marrow exam was required within 2 weeks prior to randomization. Pts were eligible if they were in a complete remission (CR) or morphologic remission (MR). Consolidation or post remission therapy prior to enrollment was allowed but not required. Pts who had received an allogeneic transplant in this remission were ineligible. Adequate blood counts (absolute neutrophil count >= 1000/mm3 and platelet count >=50,000/mm3), and normal renal, and hepatic function were required within 2 weeks of randomization. Pts were randomized to either receive tipifarnib twice daily (BID) or to observation. The main objective of this study was to compare disease free survival in the two groups. Although the study has completed accrual, an insufficient number of events have been recorded at this point to allow for evaluation of the survival data. However, toxicity data are now available. Between August 2004 and December 2009, 144 pts were accrued to the study. The median age of the pts is 70 (range 28–86). Seventy-three pts (51%) were male and 135 pts (94%) were white. Seventy-three pts were enrolled onto the treatment arm (Arm A) and 71 pts were enrolled onto the observation arm (Arm B). When the study was initially opened, pts on Arm A were treated with tipifarnib at a dose of 400 mg BID with dose reductions and interruptions defined per protocol for toxicity. After the first planned interim analysis, based on toxicity data, the ECOG Data Monitoring Committee recommended that the starting dose be decreased to 300 mg BID. The majority of pts enrolled on the study were in first CR (CR1) (Table 2). Among the 30 pts treated with the initial 400 mg BID dose, 23 pts (77%) had their dose held or reduced to a lower dose in the subsequent treatment cycles. For the 41 pts whose initial dose was 300 mg BID, 61% required either dose modification (n=19) or discontinued (n=6) due to toxicity. Table 1: Baseline characteristics Arm A 400 mg BID n=31 Arm A 300 mg BID n=42 Arm B Observation n=71 CR1 16 (52%) 34 (81%) 47 (66%) >CR1 10 (32%) 8 (19%) 16 (23%) Unknown 5 (16%) 16 (11%) Table 2: Toxicity Toxicity Type Arm A 400 mg n=31 Arm A 300 mg n=41 Arm B Observation n=69 Grade (n) Grade (n) Grade (n) 3 4 3 4 3 4 Hemoglobin 1 1 6 1 1 2 Leukocytes 2 4 16 4 3 Neutrophils 5 8 3 7 1 Platelets 4 10 11 11 1 5 Cardiac-ischemia 1 Fatigue 1 Diarrhea 1 Nausea 1 Febrile neutropenia 1 1 Infection w/gr 3-4 neutrophils (ANC) 1 Infection Gr0-2 ANC 1 1 3 GGT 1 Hypokalemia 1 Confusion 1 Agitation 1 Neuropathy-sensory 1 Back pain 1 Worst degree Non Hematologic 4 2 9 1 1 While non-hematologic toxicity was acceptable, significant hematologic toxicity was seen in pts treated at an initial dose of either 400 mg or 300 mg BID (Table 2). Of note, hematologic toxicity was also seen on the observation arm although less frequently than with both treatment doses. Non-hematologic toxicity was much less frequent overall and there were no significant non-hematologic toxicities in the observation arm. Reduction of the initial dose did not ameliorate either the hematologic or non-hematologic toxicity seen on the treatment arms. There was however no fatal toxicity at either dose level. Results of the randomization with respect to efficacy remain essential to determining the utility of this agent as maintenance therapy in AML. Disclosures: No relevant conflicts of interest to declare.