Enasidenib in the treatment of relapsed/refractory acute myeloid leukemia: an evidence-based review of its place in therapy.

Introduction: Acute myeloid leukemia (AML) remains a disease with high mortality, especially for older patients and those with relapsed/refractory (R/R) disease. With recent advances in molecular testing, targeting particular leukemogenic mutations such as those occurring in isocitrate dehydrogenase (IDH) became possible. Enasidenib is a new small-molecule inhibitor of mutant isocitrate dehydrogenase-2 (IDH2). Aim: The objective of this article is to review the evidence for the use of enasidenib in R/R AML, as well as to outline future directions of enasidenib therapy. Evidence Review: Enasidenib was approved in August 2017, after a successful Phase I/II trial showing an overall response rate (ORR) of 40.3% in R/R disease, with 19.3% of patients achieving complete remission (CR). Enrollees in the trial were mostly older adults. The most prominent toxicities were hyperbilirubinemia and IDH-differentiation syndrome (IDH-DS), though the drug was generally well tolerated and the maximum tolerated dose was not reached. A Phase III trial is currently ongoing. Conclusion: Enasidenib provides a new therapeutic option for patients with R/R AML. Further studies are ongoing to ascertain its role in combination with other agents and newly diagnosed disease.

Breast cancer-specific survival in patients with HER2-positive, node-negative T1a and T1b breast cancer.

PURPOSE: There is limited data on prognosis of node-negative (N0), HER2-positive (HER2+) small breast cancers. We evaluated breast cancer-specific survival (BCSS) among women diagnosed with T1a/T1b, N0 tumors in California between 2000-2004 and 2005-2012, eras before and after approval of adjuvant trastuzumab. PATIENTS AND METHODS: 45,346 women diagnosed with T1a/b, N0 tumors between January 1, 2000 and December 31, 2012 were identified in the California Cancer Registry (CCR); approximately 10% were HER2 + , and 80% hormone receptor positive (ER and/or PR+). Primary outcome was BCSS, analyzed in 2000-2004 and 2005-2012. Multivariable Cox proportional hazards regression was used to calculate hazard ratios and 95% confidence intervals for mortality, and separately conducted for hormone receptor positive and negative tumors. Kaplan-Meier curves compared BCSS by HER2 status. RESULTS: While BCSS in this cohort exceeded 90%, a significantly higher hazard of breast cancer death was observed in women with HER2+ tumors in the 2000-2004 era. There was no difference in outcomes between T1a and T1b tumors. Women with ER/PR+ tumors had lower hazards of death in both eras, but HER2+ tumors were associated with a higher hazard of death in the 2000-2004 era. Among women with hormone receptor negative tumors, HER2 positive disease was associated with a lower hazard of death in the 2005-2012 era. CONCLUSION: Within this large cohort of T1a/b N0 breast cancers from the CCR, HER2+ tumors were associated with a significantly worse BCSS in the era before adjuvant trastuzumab. A balanced discussion regarding HER2-directed therapies is needed between patient and clinician.