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Background The coronavirus disease 2019 (COVID‐19) pandemic has significantly impacted health care systems. However, to date, the trend of hospitalizations in the oncology patient population has not been studied, and the frequency of nosocomial spread to patients with cancer is not well understood. The objectives of this study were to evaluate the impact of COVID‐19 on inpatient oncology census and determine the nosocomial rate of COVID‐19 in patients with cancer admitted at a large academic center. Materials and Methods Medical records of patients with cancer diagnosed with COVID‐19 and admitted were reviewed to evaluate the temporal trends in inpatient oncology census during pre–COVID‐19 (January 2019 to February 2020), COVID‐19 (March to May 2020), and post–COVID‐19 surge (June to August 2020) in the region. In addition, nosocomial infection rates of SARS‐CoV‐2 were reviewed. Results Overall, the daily inpatient census was steady in 2019 (median, 103; range, 92–118) and until February 2020 (median, 112; range, 102–114). However, there was a major decline from March to May 2020 (median, 68; range, 57–104), with 45.4% lower admissions during April 2020. As the COVID‐19 surge eased, the daily inpatient census over time returned to the pre–COVID‐19 baseline (median, 103; range, 99–111). One patient (1/231, 0.004%) tested positive for SARS‐CoV‐2 13 days after hospitalization, and it is unclear if it was nosocomial or community spread. Conclusion In this study, inpatient oncology admissions decreased substantially during the COVID‐19 surge but over time returned to the pre–COVID‐19 baseline. With aggressive infection control measures, the rates of nosocomial transmission were exceedingly low and should provide reassurance to those seeking medical care, including inpatient admissions when medically necessary. Implications for Practice The COVID‐19 pandemic has had a major impact on the health care system, and cancer patients are a vulnerable population. This study observes a significant decline in the daily inpatient oncology census from March to May 2020 compared with the same time frame in the previous year and examines the potential reasons for this decline. In addition, nosocomial rates of COVID‐19 were investigated, and rates were found to be very low. These findings suggest that aggressive infection control measures can mitigate the nosocomial infection risk among cancer patients and the inpatient setting is a safe environment, providing reassurance., To understand the overall impact of COVID‐19 on health care delivery in the oncology setting, this study evaluated the inpatient oncology census, in comparison to historical data and infusion volume, at an institution with a high volume of COVID‐19 admissions.

Purpose With prospective clinical sequencing of tumors emerging as a mainstay in cancer care, an urgent need exists for a clinical support tool that distills the clinical implications associated with specific mutation events into a standardized and easily interpretable format. To this end, we developed OncoKB, an expert-guided precision oncology knowledge base. Methods OncoKB annotates the biologic and oncogenic effects and prognostic and predictive significance of somatic molecular alterations. Potential treatment implications are stratified by the level of evidence that a specific molecular alteration is predictive of drug response on the basis of US Food and Drug Administration labeling, National Comprehensive Cancer Network guidelines, disease-focused expert group recommendations, and scientific literature. Results To date, > 3,000 unique mutations, fusions, and copy number alterations in 418 cancer-associated genes have been annotated. To test the utility of OncoKB, we annotated all genomic events in 5,983 primary tumor samples in 19 cancer types. Forty-one percent of samples harbored at least one potentially actionable alteration, of which 7.5% were predictive of clinical benefit from a standard treatment. OncoKB annotations are available through a public Web resource ( http://oncokb.org ) and are incorporated into the cBioPortal for Cancer Genomics to facilitate the interpretation of genomic alterations by physicians and researchers. Conclusion OncoKB, a comprehensive and curated precision oncology knowledge base, offers oncologists detailed, evidence-based information about individual somatic mutations and structural alterations present in patient tumors with the goal of supporting optimal treatment decisions.

Purpose AKT1 E17K mutations are oncogenic and occur in many cancers at a low prevalence. We performed a multihistology basket study of AZD5363, an ATP-competitive pan-AKT kinase inhibitor, to determine the preliminary activity of AKT inhibition in AKT-mutant cancers. Patients and Methods Fifty-eight patients with advanced solid tumors were treated. The primary end point was safety; secondary end points were progression-free survival (PFS) and response according to Response Evaluation Criteria in Solid Tumors (RECIST). Tumor biopsies and plasma cell-free DNA (cfDNA) were collected in the majority of patients to identify predictive biomarkers of response. Results In patients with AKT1 E17K–mutant tumors (n = 52) and a median of five lines of prior therapy, the median PFS was 5.5 months (95% CI, 2.9 to 6.9 months), 6.6 months (95% CI, 1.5 to 8.3 months), and 4.2 months (95% CI, 2.1 to 12.8 months) in patients with estrogen receptor–positive breast, gynecologic, and other solid tumors, respectively. In an exploratory biomarker analysis, imbalance of the AKT1 E17K–mutant allele, most frequently caused by copy-neutral loss-of-heterozygosity targeting the wild-type allele, was associated with longer PFS (hazard ratio [HR], 0.41; P = .04), as was the presence of coincident PI3K pathway hotspot mutations (HR, 0.21; P = .045). Persistent declines in AKT1 E17K in cfDNA were associated with improved PFS (HR, 0.18; P = .004) and response ( P = .025). Responses were not restricted to patients with detectable AKT1 E17K in pretreatment cfDNA. The most common grade ≥ 3 adverse events were hyperglycemia (24%), diarrhea (17%), and rash (15.5%). Conclusion This study provides the first clinical data that AKT1 E17K is a therapeutic target in human cancer. The genomic context of the AKT1 E17K mutation further conditioned response to AZD5363.

Tumor molecular profiling is a fundamental component of precision oncology, enabling the identification of genomic alterations in genes and pathways that can be targeted therapeutically. The existence of recurrent targetable alterations across distinct histologically defined tumor types, coupled with an expanding portfolio of molecularly targeted therapies, demands flexible and comprehensive approaches to profile clinically relevant genes across the full spectrum of cancers. We established a large-scale, prospective clinical sequencing initiative using a comprehensive assay, MSK-IMPACT, through which we have compiled tumor and matched normal sequence data from a unique cohort of more than 10,000 patients with advanced cancer and available pathological and clinical annotations. Using these data, we identified clinically relevant somatic mutations, novel noncoding alterations, and mutational signatures that were shared by common and rare tumor types. Patients were enrolled on genomically matched clinical trials at a rate of 11%. To enable discovery of novel biomarkers and deeper investigation into rare alterations and tumor types, all results are publicly accessible.

Purpose: Advanced-stage endometrial cancers have limited treatment options and poor prognosis, highlighting the need to understand genetic drivers of therapeutic vulnerabilities and/or prognostic predictors. We examined whether prospective molecular characterization of recurrent and metastatic disease can reveal grade and histology-specific differences, facilitating enrollment onto clinical trials. Experimental Design: We integrated prospective clinical sequencing and IHC data with detailed clinical and treatment histories for 197 tumors, profiled by MSK-IMPACT from 189 patients treated at Memorial Sloan Kettering Cancer Center. Results: Patients had advanced disease and high-grade histologies, with poor progression-free survival on first-line therapy (PFS1). When matched for histology and grade, the genomic landscape was similar to that of primary untreated disease profiled by TCGA. Using multiple complementary genomic and mutational signature-based methods, we identified patients with microsatellite instability (MSI), even when standard MMR protein IHC staining failed. Tumor and matched normal DNA sequencing identified rare pathogenic germline mutations in BRCA2 and MLH1. Clustering the pattern of DNA copy-number alterations revealed a novel subset characterized by heterozygous losses across the genome and significantly worse outcomes compared with other clusters (median PFS1 9.6 months vs. 17.0 and 17.4 months; P = 0.006). Of the 68% of patients harboring potentially actionable mutations, 27% were enrolled to matched clinical trials, of which 47% of these achieved clinical benefit. Conclusions: Prospective clinical sequencing of advanced endometrial cancer can help refine prognosis and aid treatment decision making by simultaneously detecting microsatellite status, germline predisposition syndromes, and potentially actionable mutations. A small overall proportion of all patients tested received investigational, genomically matched therapy as part of clinical trials.

The cause of drug shortages is a complex issue. This commentary highlights the shortage of intravenous opioid medications for cancer patients, in light of the opioid overdose epidemic.

5545 Background: 15% of patients with OC have a germline BRCA 1 / 2 mut & 6% of OC have a somatic BRCA 1/ 2 mut. Inhibitors of poly ADP ribose polymerase (PARPi) are approved in this setting. Data is evolving as to activity of PARPi in BRCA wild type OC with somatic homologous recombination (HR) gene deficiency. We sought to determine the prevalence of somatic alterations in HR genes in an unselected cohort of epithelial OC of any histologic type. Methods: From 03/2014-10/2016 patients consented to an IRB approved protocol for tumor-normal sequencing, via a custom next-generation sequencing panel (MSK-IMPACT) with return of results for tumor mut only. Muts in 14 HR genes ( ATM, BARD1, BRCA1, BRCA2, BRIP1, CHEK1, CHEK2, FANCA, MRE11, NBN, PALB2, PTEN, RAD51D, RAD51C) and p53were assessed. Statistics were analyzed using GraphPad Prism v. 6. Results: 260 tumors were sequenced; 156 (60%) high grade serous (HGS), 34 (13%) low grade serous (LGS), 34 (13%) clear cell, 10 (4%) mucinous, 8 (3%) endometrioid, 18 (7%) mixed/other histology. 151 (97%) of HGS and 24 (23%) of the remaining tumors harbored p53 mut. 48 (18%) somatic HR mut were identified. (Table 1) 26 HGS (17%) tumors and 22 (21%) of the remaining tumors harbored a HR gene mut (HGS vs other histology, p=0.4). Notably, 8 (24%) of clear cell cancers demonstrated HR gene muts (vs HGS, p=0.3). 18 (38%) of the identified muts in the overall cohort were in BRCA 1/2. There were no somatic HR gene muts identified in the mucinous OC, which were characterized by frequent p53 (90%) and KRAS(60%) muts. Conclusions: In this cohort of OC, 17% of tumors harbor somatic HR gene muts. The prevalence of HR somatic muts was similar in HGS vs other histologies, with the exception of mucinous OC. BRCA1/2 muts predominated, however 60% of identified muts were in other genes. Accrual is ongoing to increase histologic cohort sizes. Broad HR gene somatic mutational profiling may identify a wider cohort of OC patients with potential to benefit from PARPi therapy. [Table: see text]

246 Background: Whole exome sequencing in WD pNETs demonstrated an increased number of mutations in chromatin modeling genes (MEN1, DAXX, and ATRX), and in the mTOR pathway. NGS brings this technology to the clinic but its relevance in practice has been questioned. In this prospective, IRB-approved study (NCT01775072), we used the MSK-IMPACT assay to perform NGS on WD pNETs in a routine practice setting. MSK-IMPACT, performed in a CLIA-compliant laboratory, is a multiplexed assay (Illumina HiSeq) providing full exon coverage of 410 cancer related genes, detecting base substitutions, small indels, copy number and select gene rearrangements. Methods: After written consent, tumor and germline DNA were analyzed. Genomic alterations were catalogued. Results: MSK-IMPACT results are available in 39 patients (pts). Actionable alterations were identified in 13/39 pts (33.3%). These actionable alterations included BRAF V600E (2 pts; 5.1%), and mutations in TSC1 (1 pt; 2.6%), TSC2 (5 pts; 12.8%), PTEN (4 pts; 10.3%), CDKN1B (2 pts; 5.1%), CDKN2A (2 pts; 5.1%), CDKN2B (2 pts; 5.1%), CDKN2C (1 pt; 2.6%), and ARID1A (5 pts; 12.8%). Other recurrently altered genes included MEN1 (23 pts, 59.0%), DAXX (13 pts, 33.3%), and ATRX (10 pts, 25.6%). Notably, 7 pts (17.9%) had alterations in the histone methyltransferase SETD2. All 7 pts presented with metastatic liver disease. No tumors were low grade; 6/7 (85.7%) were intermediate grade and 1/7 (14.3%) were high grade. All 7 pts received capecitabine/temozolomide (cape/tem); 6 pts (85.7%) had disease shrinkage and 1 pt (14.3%) had stable disease. Conclusions: The mutational landscape in our study was in line with prior work in pNET whole exome sequencing. In one-third of our cohort, potentially actionable alterations were identified through NGS but have not yet been shown to be therapeutically relevant. An exploratory analysis to identify responses to different therapies is ongoing. In addition, we report a novel finding of SETD2 alterations in pNETs. All pts with SETD2 alterations had intermediate to high grade tumors that responded to cape/tem. The clinical significance of SETD2 in pNETs is unknown, and evaluation using tissue microarrays is ongoing.

11583Background: Sequencing of tumor DNA is becoming part of routine clinical care, with the goal of matching patients to approved treatments or clinical trials based on specific mutations. However...