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Despite advances in the diagnosis and treatment of patients with cancer, patients with metastatic cancer have limited therapeutic options after initial lines of therapy. Understanding tumor biology has translated into the identification of actionable targets that resulted in therapeutics. Antibody-drug conjugates (ADC) are capitalizing on this explosion of scientific information. ADCs allow an antibody to a unique target to be conjugated via an innovative linker, to a highly toxic drug which is delivered to its target. Sacituzumab govitecan is an ADC that combines the active molecule in irinotecan, SN-38, to an antibody targeting trop2. Areas covered: In this review, the authors introduce the reader to the ADC sacituzumab govitecan providing the reader with details about its pharmacokinetics, pharmacodynamics, efficacy and safety. The authors also give their expert analysis about its potential future use. Expert opinion: Sacituzumab govitecan is a novel and well-tolerated therapeutic showing promising results in difficult to treat cancers. Further studies are underway to optimize the group of patients that would benefit from it. Given its excellent performance, we are cautiously optimistic it will be approved by the FDA.

PURPOSE We developed a precision medicine program for patients with advanced cancer using integrative whole-exome sequencing and transcriptome analysis. PATIENTS AND METHODS Five hundred fifteen patients with locally advanced/metastatic solid tumors were prospectively enrolled, and paired tumor/normal sequencing was performed. Seven hundred fifty-nine tumors from 515 patients were evaluated. RESULTS Most frequent tumor types were prostate (19.4%), brain (16.5%), bladder (15.4%), and kidney cancer (9.2%). Most frequently altered genes were TP53 (33%), CDKN2A (11%), APC (10%), KTM2D (8%), PTEN (8%), and BRCA2 (8%). Pathogenic germline alterations were present in 10.7% of patients, most frequently CHEK2 (1.9%), BRCA1 (1.5%), BRCA2 (1.5%), and MSH6 (1.4%). Novel gene fusions were identified, including a RBM47-CDK12 fusion in a metastatic prostate cancer sample. The rate of clinically relevant alterations was 39% by whole-exome sequencing, which was improved by 16% by adding RNA sequencing. In patients with more than one sequenced tumor sample (n = 146), 84.62% of actionable mutations were concordant. CONCLUSION Integrative analysis may uncover informative alterations for an advanced pan-cancer patient population. These alterations are consistent in spatially and temporally heterogeneous samples.

BackgroundAnticoagulation use during hemodialysis (HD) is standard practice but issues related to an increased risk of hemorrhage associated with inpatients make this a concern.MethodsAn anticoagulation-free protocol in which (i) the dialysis circuit is aggressively primed with normal saline (NS) in an attempt to flush it of all air, (ii) blood flow during the HD treatment is maximized to up to 400 mL/min, (iii) the dialysis circuit is flushed every 15 min with 100 mL of NS, and (iv) the use of bloodlines that lack a blood–air interface was developed and used for all adult inpatient HD treatments at Rush University Medical Center. The purpose of this study was to evaluate the rate of HD circuit clotting using this approach and to determine if factors such as access type, blood flow, arterial and venous bloodline pressures, the need for reversing the arterial and venous access lines for low blood flow or high venous or arterial bloodline pressures, or the amount of net ultrafiltration were associated with HD circuit clotting. Patients were excluded from analysis if they were on a heparin drip, clopidogrel, warfarin or direct thrombin inhibitors. We reviewed 400 HD treatments in 400 adult patients from 12/12 to 10/13.ResultsThe HD access in these patients consisted of catheters in 45%, native AV fistulas in 40% and grafts in 15% of the patients. The average blood flow in the treatments was 378 ± 46 mL/min. In 5% of the treatments, the arterial and venous bloodlines were reversed. Only 4 of the 400 (1%) of the treatments clotted the dialysis circuit. Factors associated with clotting were lower achieved blood flows (225 ± 50 mL/min versus 379 ± 44 mL/min), higher arterial bloodline pressures (−198 ± 24 mmHg versus −151 ± 45 mmHg) and reversal of arterial and venous access lines.ConclusionOur anticoagulation-free protocol allows inpatient HD to be performed in adults across all access types and with essentially no circuit clotting.

2557 Background: The tumor microenvironment (TME) plays a critical role in the spread of tumors. Bone marrow derived VEGFR2+endothelial progenitor cells (EPCs) and copper-dependent lysyl oxidase (LOX) are key in tumor progression. We hypothesized TM-associated copper depletion inhibits tumor metastases by reducing the number of EPCs and other copper dependent (CD) processes in the pre-metastatic niche. These results are an update with longer follow-up. Methods: Phase II study of BC pts at high risk for recurrence, defined as node+ triple negative (TNBC), stage 3 and 4 with no evidence of disease (NED) were enrolled on a trial of CD with TM. Ceruloplasmin (Cp) levels were maintained between 8-16 mg/dl for two years with an extension phase or until relapse. The primary endpoint was change in EPCs measured by flow cytometry before and during treatment. Secondary endpoints included tolerability, safety, PFS and LOXL-2 levels. Results: 75 pts received 2650 cycles of TM on primary and extension study. The median age is 51 years (range 29-66). Forty-five pts have stage 2/3 BC and 30 with stage 4 NED. TNBC pts were 48% and 40% of pts are stage 4 NED. Median Cp level decreased from 28 to 16 (p < 0.0001) after one cycle. Copper depletion was most efficient in TNBC where Cp levels dropped from 23.5 to 13 after one cycle. TM was well tolerated with grade 3/4 toxicities including: reversible neutropenia (2.3%), febrile neutropenia (0.04%), fatigue (0.2%). Five-year analysis showed a decrease in EPC’s (p = 0.004) and LOXL-2 (p < 0.001). At a median follow-up of 6.9 years, the EFS for 75 pts is 75.6%. PFS for 36 pts with TNBC is 79.2%. EFS for stage 2/3 TNBC is 90% and for stage IV TNBC is 66.7%. Conclusions: TM is safe, well tolerated and appears to affect multiple components of the TME creating an inhospitable environment for tumor progression especially in high risk patients such as TNBC. Randomized trials are warranted, especially in patients at high risk for relapse. Clinical trial information: UL1TR000457.