Selina M Luger1, Victoria X Wang2, Jacob M Rowe3, Mark R Litzow4, Elisabeth Paietta5, Rhett P Ketterling4, Hillard Lazarus6, Witold B Rybka7, Michael D Craig8, Judith Karp9, Brenda W Cooper6, Adel Z Makary10, Lynne S Kaminer11, Frederick R Appelbaum12, Richard A Larson13, Martin S Tallman14. 1. Abramson Cancer Center, University of Pennsylvania, Perelman Center for Advanced Medicine, South Tower, 12th Floor, Philadelphia, PA, PA 19104, United States. Electronic address: Selina.luger@pennmedicine.upenn.edu. 2. Dana Farber Cancer Institute-ECOG-ACRIN Biostatistics Center, Boston, AMA, United States. 3. Rambam Medical Center, Haifa, Israel. 4. Mayo Clinic, Rochester, MN, United States. 5. Montefiore Medical Center, Bronx, NY, United States. 6. Case Western Reserve University, Cleveland, OH, United States. 7. Penn State Hershey Cancer Institute, Hershey, PA, United States. 8. West Virginia University Healthcare, Morgantown, WB, United States. 9. Johns Hopkins University, Baltimore, MD, United States. 10. Geisinger Medical Center, Danville, PA, United States. 11. North Shore Health System-Evanston Hospital, Evanston, IL, United States. 12. Fred Hutchinson Cancer Research Center, Seattle, WA, United States. 13. University of Chicago, Chicago, IL, United States. 14. Northwestern University, Chicago, IL, United States(1); Memorial Sloan Kettering Cancer Center, NY, NY, United States(2).
Abstract
PURPOSE: Despite the achievement of complete remission with chemotherapy in patients with acute myeloid leukemia (AML), relapse is common and the majority of patients will die of their disease. Patients who achieve a remission after refractory or relapsed disease as well as elderly patients have a very high rate of relapse even if they achieve a complete remission. A phase 3 randomized ECOG-ACRIN-led intergroup study was conducted to determine whether post-remission therapy with the farnesyl transferase inhibitor, tipifarnib (R115777), improved the disease-free survival (DFS) of adult patients with AML in complete remission (CR), at high risk for relapse. PATIENTS AND METHODS: Adult patients with AML in remission after salvage therapy and/or over age 60 in first remission were enrolled in this study. They were randomly assigned to treatment with tipifarnib or observation (control). The primary objective was to compare the disease-free survival (DFS) between the two arms based on intention to treat, which includes all randomized patients. RESULTS: One hundred and forty-four patients were enrolled on the study. Median DFS was 8.9 vs 5.3 months, for tipifarnib vs observation (one-sided p = 0.026) and did not cross the pre-specified boundary to call the study positive. For the 134 eligible patients, median DFS was 10.8 vs 5.3 months for those randomized to tipifarnib vs observation (one-sided p = 0.008). Moreover in an ad hoc evaluation of all women (n = 71) median DFS was 12.1 vs 3.9 months for tipifarnib vs observation (one-sided p = 0.0004) while median OS was 26.5 vs 8.4 months respectively (one-sided p = 0.001). CONCLUSION: This study was not able to demonstrate a benefit to tipifarnib as maintenance therapy in patients with AML in remission. While subsets of patients may indeed benefit, additional studies would be needed to elucidate that benefit which is unlikely given that other seemingly better options have since become available.
PURPOSE: Despite the achievement of complete remission with chemotherapy in patients with acute myeloid leukemia (AML), relapse is common and the majority of patients will die of their disease. Patients who achieve a remission after refractory or relapsed disease as well as elderly patients have a very high rate of relapse even if they achieve a complete remission. A phase 3 randomized ECOG-ACRIN-led intergroup study was conducted to determine whether post-remission therapy with the farnesyl transferase inhibitor, tipifarnib (R115777), improved the disease-free survival (DFS) of adult patients with AML in complete remission (CR), at high risk for relapse. PATIENTS AND METHODS: Adult patients with AML in remission after salvage therapy and/or over age 60 in first remission were enrolled in this study. They were randomly assigned to treatment with tipifarnib or observation (control). The primary objective was to compare the disease-free survival (DFS) between the two arms based on intention to treat, which includes all randomized patients. RESULTS: One hundred and forty-four patients were enrolled on the study. Median DFS was 8.9 vs 5.3 months, for tipifarnib vs observation (one-sided p = 0.026) and did not cross the pre-specified boundary to call the study positive. For the 134 eligible patients, median DFS was 10.8 vs 5.3 months for those randomized to tipifarnib vs observation (one-sided p = 0.008). Moreover in an ad hoc evaluation of all women (n = 71) median DFS was 12.1 vs 3.9 months for tipifarnib vs observation (one-sided p = 0.0004) while median OS was 26.5 vs 8.4 months respectively (one-sided p = 0.001). CONCLUSION: This study was not able to demonstrate a benefit to tipifarnib as maintenance therapy in patients with AML in remission. While subsets of patients may indeed benefit, additional studies would be needed to elucidate that benefit which is unlikely given that other seemingly better options have since become available.
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