Eunice S. Wang, MD, on AML: Long-Term Results With Crenolanib Plus Chemotherapy
2022 ASCO Annual Meeting
Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center, discusses long-term phase II findings of a trial evaluating crenolanib plus chemotherapy in newly diagnosed adults with FLT3-mutant acute myeloid leukemia. The study showed a composite complete remission rate of 86%. With a median follow-up of 45 months, median overall survival has not been reached. A phase III trial is ongoing (Abstract 7007).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
We designed a phase II clinical trial evaluating crenolanib added to standard 7+3 intensive chemotherapy for adults with newly diagnosed FLT3 AML. The purpose of this study was to examine the efficacy of adding this novel FLT3 tyrosine kinase inhibitor to standard intensive chemotherapy based on prior results of single agent crenolanib activity in heavily pretreated relapse and refractory FLT3 mutant adult patients. Crenolanib is a pan-FLT3 inhibitor with activity against both the active and inactive formations of FLT3 and has activity against both FLT3, ITD, and TKD mutations.
We designed this study to combine it with intensive chemotherapy, for which the standard of care is currently midostaurin plus 7+3 chemotherapy. A total of 44 patients were enrolled on this study, 29 younger than equal to 60 years of age, and 15 older than 60 years of age. 91% of patients had de novo disease, 75% with FLT3 ITD mutations and 18% with TKD mutations. Overall, patients were enrolled in standard intensive therapy with physicians choice of anthracycline, daunorubicin, or idarubicin plus infusional cytarabine for 7 days, followed by crenolanib started at 24 to 48 hours after chemotherapy and continued until 72 hours prior to next chemotherapy cycle. Patients were allowed to get consolidation with high-dose cytarabine or go on to transplantation, followed by 12 months of maintenance crenolanib following either chemo or transplant.
The overall remission rate in this trial was 86%. Younger patients younger than are equal to 60 years of age had a CR/CRI rate of 90%, and individual's greater than or equal to 60 years of age had an overall response rate of 80%. At 45 months of long-term follow up, the event-free survival for all 44 patients enrolled in this trial was 45 months. The median overall survival was not reached. In younger patients younger than 60 years of age, the median overall survival was not reached, with 71% of patients alive at 3 years after enrollment on this study. The overall cumulative rate of relapse in patients was 33%, and 15% in patients younger than 60. Of note, patients undergoing transplantation in this younger cohort had similar cumulative rate of relapse than patients getting chemotherapy alone.
In conclusion, we think that this combination regimen shows high efficacy, safety, and tolerability as compared to standard 7+3 plus midostaurin. A phase III trial of this combination approach is currently accruing using midostaurin 7+3 as its control arm. Results of this trial are eagerly awaited.
Carryn M. Anderson, MD, of the University of Iowa Hospital, discusses phase III results of the ROMAN trial of avasopasem manganese for patients with severe oral mucositis who are receiving chemoradiotherapy for locally advanced, nonmetastatic head and neck cancer. Compared with placebo, avasopasem manganese improved severe oral mucositis (Abstract 6005).
Michael J. Overman, MD, of The University of Texas MD Anderson Cancer Center, and Takayuki Yoshino, PhD, MD, of the National Cancer Center Hospital East, Japan, discuss results from the PARADIGM trial, the first prospective study to test the superiority of panitumumab vs bevacizumab in combination with standard doublet first-line chemotherapy for patients with RAS wild-type and left-sided metastatic colorectal cancer. The study showed that panitumumab improved overall survival in combination with mFOLFOX6, which may establish a standard first-line combination regimen for this population (Abstract LBA1).
Martin McCabe, PhD, of the University of Manchester, discusses a phase III assessment of chemotherapy for patients with recurrent and primary refractory Ewing sarcoma. The trial, called rEECur, is the first study to provide comparative toxicity and survival data for the four most commonly used chemotherapy regimens in this disease. The analysis showed that high-dose ifosfamide is more effective in prolonging survival than topotecan plus cyclophosphamide (Abstract LBA2).
Manali I. Patel, MD, MPH, of Stanford University School of Medicine, discusses clinical trial findings on the best ways to integrate community-based interventions into cancer care delivery for low-income and minority populations. Such interventions may improve quality of life and patient activation (often defined as patients having the knowledge, skills, and confidence to manage their health), as well as reduce hospitalizations and the total costs of care (Abstract 6500).
Ann H. Partridge, MD, MPH, of Dana-Farber Cancer Institute, and Kevin Kalinsky, MD, of Winship Cancer Institute at Emory University, discuss phase II findings from the MAINTAIN trial, which showed a benefit in progression-free survival for patients with hormone receptor–positive/HER2-negative metastatic breast cancer when they switched to endocrine therapy and received ribociclib after disease progression on another CDK4/6 inhibitor (Abstract LBA1004).