ASH 2021 | Major trial outcomes at ASH 2021: PANTHER, AGILE, and LACEWING
Thomas Cluzeau, MD, PhD, Central University Hospital of Nice, Nice, France, talks on major trial outcomes in the acute myeloid leukemia (AML)/myelodysplastic syndromes (MDS) space that were shared at the ASH 2021 annual meeting. Dr Cluzeau comments on the negative Phase III PANTHER trial (NCT03268954) of pevonedistat plus azacitidine as a frontline treatment for patients with higher-risk MDS, chronic myelomonocytic leukemia (CMML), and low-blast AML. Results shared at the meeting showed that the combination failed to achieve statistical significance for the primary endpoint of event-free survival (EFS). The Phase III LACEWING trial (NCT02752035) was also presented, in which azacitidine was combined with gilteritinib for the treatment of newly diagnosed FLT3-mutated AML. The primary endpoint was not reached. Finally, Dr Cluzeau highlights the positive findings of the Phase III AGILE trial (NCT03173248) of ivosidenib plus azacitidine in untreated patients with IDH1-mutated AML, which was shown to significantly prolong EFS compared to the use of azacitidine plus placebo. This interview took place at during 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.
Transcript (edited for clarity)
During this ASH meeting, I think there are two disappointments maybe. One is the PANTHER study, evaluating azacitidine plus pevonedistat versus azacitidine plus placebo in myelodysplastic syndromes. Unfortunately, this study failed its primary endpoint. So based on the Phase II study, we guessed this Phase III would be a positive, but it wasn’t the case. Today, azacitidine stays for the moment, the standard of care for myelodysplastic syndromes...
During this ASH meeting, I think there are two disappointments maybe. One is the PANTHER study, evaluating azacitidine plus pevonedistat versus azacitidine plus placebo in myelodysplastic syndromes. Unfortunately, this study failed its primary endpoint. So based on the Phase II study, we guessed this Phase III would be a positive, but it wasn’t the case. Today, azacitidine stays for the moment, the standard of care for myelodysplastic syndromes.
The secondary disappointment is the LACEWING study evaluating azacitidine plus gilteritinib in FLT3-mutated patients. This study failed to obtain the primary endpoint too.
Maybe the third highlight is the AGILE study in acute myeloid leukemia IDH1 mutated, evaluating azacitidine plus ivosidenib in first-line randomized with AZA alone. So this study is positive. We observed a significant increase of response and also a significant increase of overall survival. So I think maybe azacitidine plus ivosidenib could challenge azacitidine plus venetoclax in first line in the IDH1-mutated patient. So maybe there is something to evaluate in the future.
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