Response Rate, Event-Free Survival, and Overall Survival in Newly Diagnosed Acute Myeloid Leukemia: US Food and Drug Administration Trial-Level and Patient-Level Analyses. Issue 8 (10th March 2022)

• Record Type: Journal Article
• Authors: Norsworthy, Kelly J.; Gao, Xin; Ko, Chia-Wen; Pulte, E. Dianne; Zhou, Jiaxi; Gong, Yutao; Shen, Yuan Li; Vallejo, Jonathon; Gwise, Thomas E.; Sridhara, Rajeshwari; Deisseroth, Albert B.; Farrell, Ann T.; de Claro, R. Angelo; Blumenthal, Gideon M.; Pazdur, Richard
• Is Part Of: Journal of clinical oncology. Volume 40:Issue 8(2022)
• Page Start: 847
• Page End: 854
• Publication Date: 2022-03-10
• Subjects: Oncology -- Periodicals; Cancer -- Periodicals; Oncology; Medical Oncology; Cancérologie -- Périodiques; Cancer -- Périodiques; Cancérologie; Cancer; Oncology; Oncologia; Càncer; Periodicals; 616.994
• DOI: 10.1200/JCO.21.01548
• Languages: English
• ISSNs: 0732-183X

Abstract

Abstract : PURPOSE: To explore trial-level and patient-level associations between response (complete remission [CR] and CR + CR with incomplete hematologic [CRi] or platelet [CRp] recovery), event-free survival (EFS), and overall survival (OS) in newly diagnosed acute myeloid leukemia (AML) trials of intensive chemotherapy. METHODS: We identified data from eight randomized, active-controlled trials of intensive chemotherapy submitted to the US Food and Drug Administration for treatment of newly diagnosed AML (N = 4, 482). Associations between trial-level odds ratios (ORs) for CR and CR + CRi or CRp, and hazard ratios (HRs) for EFS and OS were analyzed using weighted linear regression models. We performed patient-level responder analyses to compare OS by response using pooled data from all studies. RESULTS: In trial-level analyses, association between HR for OS and OR for CR was moderate (R 2 = 0.49; 95% CI, 0.05 to 0.86), as was the association with OR for CR + CRi or CRp (R 2 = 0.48; 95% CI, 0.05 to 0.99). For OS versus EFS, a strong association was observed (R 2 = 0.87; 95% CI, 0.47 to 0.98) when EFS definitions were harmonized across trials using raw data. In the patient-level responder analyses, patients who achieved CR had better OS compared with CRi or CRp responders (0.73; 95% CI, 0.64 to 0.84) and nonresponders (HR, 0.33; 95% CI, 0.31 to 0.37). CONCLUSION: On a trial level, there is a moderate association between OS and CR rate. A strong association between EFS and OS was observed. However, CIs were wide, and results became moderate using alternative definitions for EFS. Patient-level analyses showed CR responders have better OS compared with CRi or CRp responders and nonresponders. A therapy in newly diagnosed AML with benefit in EFS or substantial benefit in CR rate would be likely to have an OS effect. Abstract :