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
Benoit You, MD, PhD, of Lyon University hospital (HCL, France) and GINECO group (France), discusses findings from the GOG-0218 trial of patients with ovarian cancer, which appears to confirm earlier data on the link between poor tumor chemosensitivity and benefit from concurrent plus maintenance bevacizumab. In Dr. You’s validation study, patients who derived the most progression-free and overall survival benefit from bevacizumab were those with high-risk disease (stage IV or incompletely resected stage III) associated with an unfavorable KELIM score (CA-125 kinetic elimination rate constant, calculable online) (Abstract 5553).
The ASCO Post Staff
Sumanta K. Pal, MD, of City of Hope National Medical Center, discusses findings from the COSMIC-021 study, which showed that cabozantinib plus atezolizumab demonstrated encouraging clinical activity with manageable toxicity in patients with inoperable locally advanced or metastatic urothelial carcinoma. The combination was administered as first-line therapy in cisplatin-based chemotherapy–eligible and –ineligible patients and as second- or later-line treatment in those who received prior immune checkpoint inhibitors (Abstract 4504).
The ASCO Post Staff
Alicia K. Morgans, MD, MPH, of Dana-Farber Cancer Institute, and Ian D. Davis, PhD, MBBS, of Monash University and Eastern Health, discuss the latest findings from ANZUP Cancer Trials Group’s ENZAMET cooperative group trial of enzalutamide in patients with metastatic hormone-sensitive prostate cancer. The results corroborate the benefit of enzalutamide with improved overall survival, and involve some exploratory subgroup analyses (Abstract LBA5004).
Karim Chamie, MD, of the University of California, Los Angeles, discusses final clinical results on combining the superagonist N-803 with bacillus Calmette-Guérin (BCG) in patients whose carcinoma in situ and high-grade non–muscle-invasive bladder cancers are unresponsive to BCG alone. Of note, cystectomy was avoided in more than 90% of patients with 2 years of follow-up (Abstract 4508).