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).
Transcript
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.
The ASCO Post Staff
Richard Finn, MD, of the Geffen School of Medicine at UCLA and the Jonsson Comprehensive Cancer Center, discusses analyses from the PALOMA-2 trial on overall survival with first-line palbociclib plus letrozole vs placebo plus letrozole in women with ER-positive/HER2-negative advanced breast cancer. The study met its primary endpoint of improving progression-free survival but not the secondary endpoint of overall survival. Although patients receiving palbociclib plus letrozole had numerically longer overall survival than those receiving placebo plus letrozole, the results were not statistically significant (Abstract LBA1003).
The ASCO Post Staff
Stephen M. Ansell, PhD, MD, of Mayo Clinic, discusses updated data from the ECHELON-1 trial, which showed that, when administered to patients with stage III or IV classical Hodgkin lymphoma, the combination of brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) vs doxorubicin, bleomycin, vinblastine, and dacarbazine resulted in a 41% reduction in the risk of death. These outcomes, says Dr. Ansell, confirm A+AVD as a preferred option for previously untreated disease (Abstract 7503).
The ASCO Post Staff
Tara B. Sanft, MD, of Yale University, discusses the results of the LEANer study (Lifestyle, Exercise, and Nutrition Early After Diagnosis) in women with breast cancer. It showed that patients with newly diagnosed disease who were just starting chemotherapy could improve physical activity and diet quality. While both groups had high rates of treatment completion, women in the intervention who exercised at or above the recommended levels did better in terms of treatment completion, with fewer dose reductions and delays (Abstract 12007).
The ASCO Post Staff
Robert Hugh Jones, MD, PhD, of Cardiff University and Velindre Hospital, discusses results from an updated analysis of the FAKTION trial, which showed improved overall survival with fulvestrant plus capivasertib in women with metastatic estrogen receptor–positive breast cancer whose disease had relapsed or progressed on an aromatase inhibitor. The benefit may be predominantly in patients with PIK3CA/AKT1/PTEN pathway–altered tumors, a topic researchers continue to study in the phase III CAPItello-291 trial (Abstract 1005).
The ASCO Post Staff
Alfredo Carrato, MD, PhD, of Alcala de Henares University in Spain, discusses phase II results from the SEQUENCE trial, which showed that nab-paclitaxel, gemcitabine, and modified FOLFOX showed significantly higher clinical activity than the standard nab-paclitaxel and gemcitabine in the first-line setting of patients with untreated metastatic pancreatic ductal adenocarcinoma (Abstract 4022).