After the U.S. Food and Drug Administration’s (FDA’s) Oncologic Drugs Advisory Committee decided against recommending approval of quizartinib for patients with relapsed/refractory FLT3-ITD acute myeloid leukemia, the agency issued a complete response letter declining to approve the agent. However, Japan’s Ministry of Health, Labor and Welfare approved quizartinib for this indication.
Japan’s approval was based on results from the phase III QuANTUM-R study, in which the second-generation tyrosine kinase inhibitor met the primary endpoint for improvement in overall survival (OS), compared with chemotherapy. Treatment with quizartinib demonstrated a statistically significant improvement in OS (hazard ratio = 0.76; p value not reported) and median OS (6.2 months vs. 4.7 months; p value not reported).
The most common treatment-related adverse events (AEs) included nausea (33.2%), electrocardiogram prolonged QT interval (24.9%), anemia (24.9%), and thrombocytopenia (21.2%).
However, in their review of the data, FDA members could not determine that the benefits of quizartinib treatment outweighed its risks, citing a lack of improvement in event-free survival and concerns about quizartinib’s cardiac-related AEs. The agency also noted issues with the credibility and generalizability of the trial’s data. For example, 23% of patients assigned to the chemotherapy group did not receive study treatment and were not followed, compared with 2% of patients assigned to the quizartinib group. This disparity “is quite bothersome as to whether this is an adequate and well-controlled study,” said the FDA’s Richard Pazdur, MD, director of the agency’s Oncology Center of Excellence.
Daiichi Sankyo, the manufacturer of quizartinib, responded that it was unable to follow certain patients who opted to be treated outside of the study’s protocol due to discrepancies in international and regional regulations governing the withdrawal of consent.
The company said it is evaluating next steps for quizartinib in the U.S.
Sources: Daiichi Sankyo press release, May 15, 2019; Daiichi Sankyo press release, June 18, 2019.