9044 Background: Osimertinib is an oral third generation irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). In the FLAURA trial (a Phase III randomized-control trial) Osimertinib arm had higher rate of cardio-toxicity compared to standard EGFR-TKIs. We queried FAERS database to find out rate of cardio-toxicity caused by Osimertinib compared to other EGFR-TKIs. Methods: We queried FAERS for “Cardiac failure”, “Electrogram QT-prolonged”, “Atrial Fibrillation(A.fib)”, “Myocardial Infarction(MI)”, “Cardiac failure congestive(CFC)” and “Pericardial Effusion(PE)” secondary to “Osimetinib”, “Erlotonib”, “Afatinib” and “Gefitinib” from 2016-2018. Disproportionality signal analysis was done by calculating Reporting Odds Ratio (ROR) with 95% confidence interval (CI). ROR was considered significant when lower limit of 95% CI was > 1. Results: Total AEs from all drugs were 5,138,230. Total AEs from all 4 TKIs were 8450, 2454 due to Osimertinib, 5836 due to other TKIs and 160 due to combination of both Osimertinib plus any of other 3 TKIs. ROR for Cardiac failure, A.fib, QT prolongation, MI, PE and CFC due to Osimertinib was 6.4(4.7-8.7), 4(2.8-5.8), 11.2(7.9-15.8), 1.6(0.9-2.6), 8.2(4.8-14) and 3.9(2.4-6.3) respectively. ROR for Cardiac failure, A.fib, QT prolongation, MI, PE and CFC on comparing Osimertinib vs other TKIs was 2.1(1.3-3.2), 2.1(1.3-3.5), 6.6(3.4-12.8), 1.2(0.6-2.3), 1.6(0.8-3.3) and 2.3(1.2-4.6) respectively. Findings are summarized in Table. Conclusions: Rate of QT prolongation, cardiac failure, CFC and A.fib were found to be higher due to Osimertinib compared to other TKIs. EKG monitoring for QT prolongation and monitoring for signs/symptoms of heart failure should be considered while using Osimertinib. [Table: see text]

Chimeric antigen receptor T-cells (CAR-T) are improving outcomes in pediatric and adult patients with relapsed or refractory B-cell acute lymphoblastic leukemias and subtypes of non-Hodgkin Lymphoma. As this treatment is being increasingly utilized, a better understanding of the unique toxicities associated with this therapy is warranted. While there is growing knowledge on the diagnosis and treatment of cytokine release syndrome (CRS), relatively little is known about the associated cardiac events that occur with CRS that may result in prolonged length of hospital stay, admission to the intensive care unit for pressor support, or cardiac death. This review focuses on the various manifestations of cardiotoxicity, potential risk factors, real world and clinical trial data on prevalence of reported cardiotoxicity events, and treatment recommendations.

Nearly 50% of uveal melanoma (UM) patients develop metastatic disease, and there remains no current standard assay for detection of minimal residual disease. We conducted a pilot study to check the feasibility of circulating tumor cell (CTC) detection in UM. We enrolled 40 patients with early or metastatic UM of which 20 patients had early-stage disease, 19 had metastatic disease, and one was not evaluable. At initial blood draw, 36% of patients had detectable CTCs (30% in early-stage vs. 42% in metastatic), which increased to 54% at data cutoff (40% in early-stage vs. 68% in metastatic). Five early-stage patients developed distant metastases, 60% (3/5) had detectable CTCs before radiographic detection of the metastasis. Landmark overall survival (from study enrollment) at 24 months was statistically lower in CTC-positive vs. negative early-stage UM (p < 0.05). Within this small dataset, the presence of CTCs in early-stage UM predicted an increased risk of metastatic disease and was associated with worse outcomes.

A phase 1/2 clinical trial in patients with chemoresistant triple-negative breast cancer targets the inducible nitric oxide signaling pathway.

BackgroundImmune checkpoint inhibitors that block programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) have improved outcomes for many cancer subtypes but do exhibit toxicity, in the form of immune-related adverse events.ObjectiveThe aim of this study was to investigate the emerging toxicities of PD-1 and PD-L1 inhibitors including acute or reactivation of tuberculosis (TB) and atypical mycobacterial infection (AMI).MethodsThis study was completed as a retrospective review using the US Food and Drug Administration Adverse Events Reporting System (FAERS) for incidence of TB and AMI due to PD-1 and PD-L1 inhibitors compared with other FDA (Food and Drug Administration) approved drugs. The statistical methods included disproportionality signal analysis using the reporting OR (ROR) to compare cases. The 95% Wald CI was reported to assess the precision of the ROR.ResultsOut of the 10 146 481 adverse events (AEs) reported to FAERS for all drugs between 1 January 2015 and 31 March 2020, 73 886 AEs were due to the five FDA approved PD-1/PD-L1 inhibitors. Seventy-two cases of TB were due to PD-1/PD-L1 inhibitors. Specifically, 45 cases (62.5%) due to nivolumab, 18 (25%) due to pembrolizumab, 5 (7%) due to atezolizumab and 4 (5.5%) due to durvalumab. There were 13 cases of AMI: 9 (69.3%) due to nivolumab, 2 (15.3%) due to pembrolizumab and 1 (7.7%) each due to durvalumab and atezolizumab. Avelumab was not attributed to any AE of TB or AMI. From analysis of the FAERS database, the calculated ROR for TB due to PD-1/PD-L1 inhibitors was 1.79 (95% CI, 1.42 to 2.26) (p<0.0001) and for AMI was 5.49 (95% CI, 3.15 to 9.55) (p<0.0001).ConclusionPD-1/PD-L1 inhibitors used in the treatment of cancer subtypes is associated with increased TB and AMI risk. Although this complication is rare, clinicians using PD-1/PD-L1 inhibitors should be aware of the risks.