Abemaciclib is an effective and well-tolerated treatment for HR-positive, HER2-negative advanced or metastatic breast cancer.

Background. The combination of everolimus (EVE) and exemestane (EXE) is approved for the treatment of metastatic hormone receptor-positive breast cancer (mHRBC) patients who progress on non-steroidal aromatase inhibitor (NSAI) therapy. However, none of the subjects enrolled in the trial that led to this approval (BOLERO-2) had previously received CDK4/6 inhibitors (CDK4/6is), which have since become a frontline standard of care for mHRBC. As such, the clinical benefit of EVE + EXE in patients who have previously received CDK4/6is remains unknown. Methods. Adult mHRBC patients at our institution who progressed on a NSAI + CDK4/6i or NSAI therapy alone and were treated with at least one cycle of EVE + EXE between 2012 and 2018 were analyzed. Collected data included patient demographics, treatment history, adverse events, and clinical outcomes. Primary objectives were to compare progression-free survival (PFS) and overall survival (OS) between patients who received prior NSAI + CDK4/6i therapy versus a NSAI alone. Results. Among 43 patients, 17 had prior CDK4/6i exposure. With the exception of de novo metastatic disease, patient and disease characteristics were comparable across treatment cohorts. There was no significant difference in PFS (median 3.6 vs 4.2 months) or OS (median 15.6 vs 11.3 months) between patients who had received prior CDK4/6is and those who had not, respectively. Conclusion. Prior exposure to CDK4/6i therapy did not impact survival outcomes for mHRBC patients taking EVE + EXE. However, there was a trend towards improved OS in the CDK4/6i cohort that should be evaluated in larger cohorts. The Oncologist 2020;9999:• • Implications for Practice: The use of CDK4/6 inhibitors in combination with a non-steroidal aromatase inhibitor has become a standard frontline therapy in metastatic hormone receptor-positive breast cancer. An approved subsequent line of therapy is everolimus plus exemestane however the original data supporting this therapy predated prior of approval CDK4/6 inhibitors. As such, the clinical benefit of everolimus and exemestane in patients previously treated with a CDK4/6i was unknown. This retrospective cohort study offers real world data demonstrating prior CDK4/6 inhibitor exposure does not impact survival outcomes for everolimus plus exemestane.

No abstract

The incidence and mortality of melanoma are on the rise. Historically, patients diagnosed with metastatic melanoma were faced with a grim prognosis, with survival rates of 15% at 5 years. Prior to 2011, no drug or therapeutic regimen had been shown to improve overall survival (OS) in metastatic melanoma. Chemotherapeutic agents, such as dacarbazine or temozolomide, are often given to patients for palliative purposes; high-dose interleukin 2 and biochemotherapy are immunotherapeutic options that could be offered to patients with a good performance status at specialized centers. Neither has been shown to impact OS, but durable complete responses are seen in a minority of patients. Since 2011, 4 new drugs have been approved by the US Food and Drug Administration for the treatment of metastatic melanoma, all of which improve survival. Three of these agents (vemurafenib, dabrafenib, and trametinib) are targeted therapies, with ipilimumab being the only new immunotherapy. With a focus on immunotherapeutic agents, this review seeks to summarize the treatment options currently available for metastatic melanoma and to examine those on the near horizon.

In July 2013, the US Food and Drug Administration approved levomilnacipran extended release (ER; Fetzima), a serotonin-norepinephrine reuptake inhibitor, for the treatment of adults with major depressive disorder. Levomilnacipran is an active enantiomer of the racemic drug milnacipran that is currently approved in the United States for the treatment of fibromyalgia. This article provides an overview of the mechanism of action, pharmacokinetic properties, clinical efficacy, safety, and tolerability of levomilnacipran ER. Relevant information was identified through a search of databases using the key word levomilnacipran. Additional information was obtained from fda.gov, by a review of the reference lists of identified articles, and from posters and abstracts from scientific meetings. Levomilnacipran ER, dosed once daily, is generally well tolerated and has demonstrated favorable effects compared to placebo in clinical trials of patients with major depressive disorder. The increased potency for norepinephrine reuptake inhibition is a characteristic that may represent a novel contribution for levomilnacipran. Additional studies comparing levomilnacipran ER to other commonly prescribed antidepressants are needed to further evaluate its place in therapy.