Study details
The QUAZAR phase 3 study enrolled patients with poor- or intermediate-risk cytogenetics who had an Eastern Cooperative Oncology Group performance status less than or equal to 3 and who had achieved CR or CR with incomplete count recovery (CRi) after induction therapy with or without consolidation therapy. In addition, patients were not candidates for stem cell transplants.
Patients had predominantly de novo AML (89%). Other baseline characteristics of note:
- 85% of patients had intermediate-risk and 15% had poor-risk cytogenetics
- 79% achieved CR and 21% achieved CRi after induction therapy
- 78% received at least one cycle of consolidation therapy
- 43% of patients had minimal residual disease (MRD)–positive disease
Patients were randomized to receive oral azacitidine 200 mg daily on days 1-14 of a repeat 28-day cycle (n = 278) or matching placebo (n = 274). Treatment was continued indefinitely until blast count was more than 15% or patients experienced unacceptable toxicity or went on to transplant.
At a median follow-up of over 41.2 months (3 years, 5 months), median overall survival was significantly longer for patients receiving oral azacitidine at 24.7 months versus 14.8 months for placebo (P less than .0009; hazard ratio, 0.69).
Relapse-free survival was also significantly prolonged, to 10.2 months for patients on oral azacitidine versus 4.8 months for placebo (HR, 0.65; P less than .0001).
Patients on oral azacitidine reported more grade 1-2 gastrointestinal adverse events, such as nausea (65% vs. 24% on placebo), vomiting (60% vs. 10%), and diarrhea (50% vs 22%), as well as more cytopenia. The most common grade 3-4 adverse events were neutropenia (41% with oral azacitidine vs. 24% on placebo), thrombocytopenia (23% vs. 22%), and anemia (14% vs. 13%).
Although Dr. Erba supported the use of oral azacitidine as maintenance therapy, he pointed out that it was hard to convince patients, especially older ones, to continue on maintenance therapy indefinitely. “The toxicities of continuing on a drug indefinitely are real issues,” he said, explaining that most elderly patients cannot cope with even grade 1-2 nausea, diarrhea, and vomiting over the long term.
But he noted that, regardless of the higher incidence of some adverse events with oral azacitidine, the health-related quality of life of patients on oral azacitidine was similar to those on placebo.
Awaiting longer follow-up
Both experts said that longer-term follow-up is needed.
“We need a longer follow-up to see how the curves plateau,” Dr. Erba said. He would also like to see a comparative analysis of the data in patients who are MRD negative versus those who are MRD positive.
“The final results of this study, including the impact of measurable residual disease on outcome in this setting, will potentially have practice-changing implications,” said Dr. Mascarenhas.
At the press conference, Dr. Wei pointed out that, based on the data from QUAZAR, oral azacitidine is likely to be evaluated in the frontline setting of AML. “The elderly make up about two-thirds of all AML patients, and oral azacitidine will be a better option than 7 days per month for chemotherapy treatment in the clinic,” he said. “Oral azacitidine in the future may also be the backbone for other combinations.”
The study was funded by Celgene.
Dr. Wei receives honoraria from AbbVie, Macrogenics, Pfizer, Astellas, Janssen, Servier, Celgene, Amgen, AstraZeneca, Novartis, and Genentech; is on the board of directors or serves on the advisory committees for AbbVie, Macrogenics, Pfizer, Astellas, Servier, Celgene, Amgen, Novartis, and Genentech; and receives research funding from AbbVie, Servier, Celgene, Amgen, AstraZeneca, and Novartis. As a former employee of the Walter and Eliza Hall Institute, Dr. Wei receives a fraction of its royalty stream related to venetoclax.
A partial list of Dr. Erba’s conflict of interest includes consulting with Agios, Novartis, Daiichi Sankyo, MacroGenics, Jazz Pharmaceuticals, Seattle Genetics, GlycoMimetics, Amgen, Pfizer, Celgene, AbbVie, Covance, Immunogen, Astellas Pharma, Incyte; being on the speakers bureau or receiving lecture fees from Agios, Novartis, MacroGenics, Jazz Pharmaceuticals, Celgene; receiving research funding from Novartis, Daiichi Sankyo, MacroGenics, GlycoMimetics, Celgene; being on the data and safety monitoring board of GlycoMimetics; and chairing independent review boards for several trials across several companies.
A version of this story originally appeared on Medscape.com.