tbuckley/cabot-search huggingface dataset:
Phase II trial of pembrolizumab (pembro) plus 1 mg/kg ipilimumab (ipi) immediately following progression on anti-PD-1 Ab in melanoma (mel).
Authors: Daniel Olson, Jason J. Luke, Sigrun Hallmeyer, Madhuri Bajaj, Timothy Carll, Thomas Krausz, Yuanyuan Zha, Theodore Karrison, Bruce Brockstein, Vernon K. Sondak, Zeynep Eroglu, Thomas Gajewski, Nikhil I. Khushalani
Journal: Journal of Clinical Oncology (2018)

9514 Background: Immunotherapy with anti-PD-1 + CTLA-4 Abs improves response rates over anti-PD-1 Ab alone; however, the utility of this combination after first line anti-PD-1 is unknown. We report the first prospective data evaluating pembro + low dose ipi immediately following progression on anti-PD-1 (NCT02743819). Methods: Patients (pts) with mel and measurable disease, no autoimmunity, and no prior anti-CTLA-4 who had progressed immediately prior on an anti-PD-1 (or non-CTLA4 combination) were eligible. Prior BRAF inhibitor was allowed (none received it). Pts received pembro 200 mg + ipi 1 mg/kg Q3W for 4 doses, then pembro alone. The primary endpoint was response rate (RR) as assessed by irRECIST. An optimal Simon two-stage design was employed to test the null hypothesis of a 10% RR vs 30% alternative (1-sided alpha 0.10, 90% power, ≥2/12 RR to continue to total of ≥6/35). The data analysis cutoff date was January 2, 2018. Results: 22 patients have been accrued with 17 evaluable for the primary endpoint (4 have not yet had their first imaging evaluation and 1 was not enrolled). Prior treatment included 21 on anti-PD-1 alone and 1 on combination with IDO inhibitor. Median length of treatment on prior anti-PD-1 was 5.6 months among all 22 pts. The study met its interim efficacy analysis with 5/12 responses to move to stage 2. Among the 17 response-evaluable pts there were 2 CR, 6 PR (47% RR), and 5 SD for disease control rate (DCR) of 76% and rejection of the null hypothesis. Progression-free survival at 6 months was 75% (CI 47%-90%). All responses are ongoing. At last follow-up, 8 pts have gone off treatment with 14/22 (64%) having any drug-related and 3/22 (14%) ≥ grade 3-4 drug-related AE (hyperglycemia, acute kidney injury and skin tissue disorder, diarrhea and rash acneiform). Among 11 response-evaluable pts with staining results currently available, RR and DCR were 67% and 100% in PD-L1+ (n = 3) and 50% and 88% in PD-L1 negative (n = 8) tumors. Further biomarker analysis is underway. Conclusions: Pembro + 1 mg/kg ipi is tolerable and has antitumor activity in pts with mel who have progressed immediately prior on an anti-PD-1 Ab. The trial sample size has been expanded to further explore this regimen. Clinical trial information: NCT02743819.
Treatment regimens and duration of lines of therapy in Medicare-enrolled patients with multiple myeloma.
Authors: Akeem Yusuf, Tanya Natwick, Diana Felici, Winifred Werther
Journal: Journal of Clinical Oncology (2016)

8046 Background: Multiple myeloma (MM) patients are often treated with multiple lines of therapy (LOT). The aim of this study is to describe the use of drug regimens by LOT and to describe the duration of LOT in Medicare MM patients. Methods: Using a validated algorithm, adult MM patients (2008-2011) were identified from the 100% Medicare hematologic cancer file. Patients receiving treatments were identified for LOT from 1 to 4 lines. Drug regimens were based on National Comprehensive Cancer Network MM treatment guidelines and were identified using National Drug Code and Health Care Procedure Coding System codes. Drug regimens included proteasome inhibitor (PI): bortezomib; immunomodulatory agents (IMiD): lenalidomide, thalidomide; PI/IMiD combinations; and other chemotherapies. Duration of LOT was defined from first drug prescription or administration to the start of the subsequent LOT, death, disenrollment, or end of data (2012). Results: 15474, 8308, 3878, and 1608 MM patients initiated 1st, 2nd, 3rd, and 4th LOTs, respectively. Regimen distributions by LOT were similar for lines 1-4 with 24-30%, 28-30%, 10-12%, and 31-37% of patients treated with PI, IMiD, PI/IMiD, and other chemotherapies, respectively. The mean duration of LOT 1, 2, 3, and 4 was 386, 329, 268, and 232 days, respectively. The median duration of LOT 1, 2, 3, and 4 was 284, 241, 199, and 177 days, respectively. Conclusions: In the Medicare MM population, the distribution of treatment regimens including PI, IMiD drugs, and other chemotherapies were similar across lines 1 through 4. The duration of LOT decreased from line 1 to 4. These data provide insights into real world use of MM treatments. IMiD448829426(343) IMiD448829426(322) Regimen distribution by line of therapy. N % Duration Number of days mean (median) Line 1 Line 1 PI 4693 30 362(268) IMiD 4488 29 426(322) PI/IMiD 1546 10 416(343) Other 4747 31 360(245) Line 2 Line 2 PI 1999 24 308(226) IMiD 2493 30 366(274) PI/IMiD 971 12 333(247) Other 2845 34 309(217) Line 3 Line 3 PI 924 24 237(185) IMiD 1135 29 316(231) PI/ImiD 482 12 276(206) Other 1337 34 245(182) Line 4 Line 4 PI 378 24 222(182) IMiD 446 28 265(204) PI/IMiD 194 12 246(189) Other 590 37 209(158)
Clinical outcomes in patients with advanced NSCLC treated with targeted therapies, with actionable mutations identified by InVisionFirst ctDNA assay
Authors: J. Remon, L. Mezquita, S. Ortiz-Cuaran, C. Jovelet, L. Lacroix, C. Morris, E. Green, P. Saintigny, B. Besse, A. Swalduz, K. Howarth, E. Rouleau, F. De Kievit, K. Baker-Neblett, S. Roitt, V. Plagnol, M. Perol, D. Planchard
Journal: Annals of Oncology (2018)

Background: ctDNA-based molecular profiling of advanced cancer patients with multi-gene next-generation sequencing (NGS) panels is rapidly gaining traction in clinical practice given faster results and more comprehensive stratification. However, clinical outcomes of patients with genomic alterations in plasma ctDNA by NGS panels remain poorly described. Here, we describe outcomes in advanced NSCLC patients with actionable alterations identified in plasma by InVisionFirst™-Lung. Methods: A pooled-analysis across advanced NSCLC patients with actionable alterations detected by amplicon-based NGS (InVisionFirst) analysis was performed. Patients treated with matched targeted therapies evaluable for disease control at 3 months were collated for clinical outcomes analysis, based on disease stage and class of therapy. All patients provided written consent approved by the institutional ethics committee under which the studies were conducted. Results: Of 82 patients evaluable for outcome analyses, 71 patients (87%) had disease control at 3 months of therapy with a 61% response rate. Breakdown of patients by disease setting and by genomic alteration along with their 3-month disease control rate are shown in the table below.Table: 24PSummary of patient disease control at 3 months by actionable variantPrior therapy for advanced diseaseGenomic alterationNNumber still on targeted therapy, no PD at 3 months% still on targeted therapy, no PD at 3 monthsUntreated for advanced diseaseAll EGFR mutation Braf v600 mutation ALK / ROS1 fusion9 6 2 17 5 1 178% 83% 50% 100%Prior cytotoxic chemotherapy for advanced disease but no targeted therapyAll EGFR mutation Braf v600 mutation ALK / ROS1 fusion18 9 2 716 8 1 789% 89% 50% 100%Prior therapy with targeted therapyAll EGFR mutation (49 with T790) ALK / ROS1 fusion55 49 648 42 687% 86% 100%Overall827187% Open table in a new tab Conclusions: Clinical outcomes in patients who have been treated with targeted therapy based on actionable alterations detected by amplicon-based NGS ctDNA analysis by InVisionFirst are consistent with those reported based on tissue profiling. ctDNA molecular profiling using InVisionFirst is an accurate and reliable tool for the detection of clinically relevant molecular alterations in advanced NSCLC patients. Legal entity responsible for the study: Inivata Ltd. Funding: Inivata Ltd. Disclosure: C. Morris, E. Green: Inivata employee and shareholder. All other authors have declared no conflicts of interest.
Prognosis and survival of stage I endometrial stromal sarcoma (ESS) and uterine adenosarcoma: Analysis of the National Cancer Database (NCDB).
Authors: Devalkumar Rajyaguru, Andrew Borgert, Angela Smith
Journal: Journal of Clinical Oncology (2018)

e17569 Background: Surgery is potentially curative in patients with stage I Endometrial Stromal Sarcoma (ESS) and uterine adenosarcoma; however, 20-40% patients will develop recurrence, suggesting need for effective adjuvant therapy. However, role of adjuvant therapy in resected stage I ESS and uterine adenosarcoma is controversial. We compared the effectiveness of adjuvant chemotherapy and radiation (RT) in patients with resected stage I ESS and adenosarcoma using the national cancer database (NCDB). Methods: We identified patients who underwent definitive surgery for stage I ESS and uterine adenosarcoma between 2010 and 2013 from NCDB. Patients with low grade ESS and positive margins were excluded. Kaplan-Meier and multivariate survival analyses were performed to investigate predictors of survival. Propensity score (matched and weighted) analyses were performed to evaluate the roles of adjuvant chemotherapy and radiation. Results: Overall 201 and 342 patients underwent definitive surgery for stage I ESS and uterine adenosarcoma, respectively. Among eligible patients, 49 (24.4%) and 31 (9.1%) received adjuvant chemotherapy for resected stage I ESS and uterine adenosarcoma. Older age, low income, stage IB/IC and poorly differentiate/undifferentiated histology were independently associated with decreased survival by unmatched cohort analyses. The propensity -matched cohort included 209 patients with baseline characteristics well balance between botharms. After propensity matching, 5-year OS was 60.7% (95% CI, 43.8% to 73.9%) in patients who received adjuvant chemotherapy compared with 74.4% (95% CI, 67.2% to 80.2%) in the surgery alone arm (p = 0.1). Omitting RT,oophorectomy, lymphadenectomy or omentectomy was not associated with increased survival in matched analysis. Conclusions: Observation should remain the standard of care and adjuvant therapy with chemotherapy or radiation is ineffective for resected stage I ESS and adenosarcoma. Oophorectomy, omentectomy and lymphadenectomy may be safely omitted for stage I ESS and adenosarcoma. Novel regimens/approaches should be investigated to improve outcomes for resected ESS and uterine adenosarcoma.
Abstract 20215: Bedside Transcranial Dopplersonography for Prognostication After Cardiac Arrest
Authors: Antje Reichenbach, Lars Alteheld, Julia Henriksen, Espen R Nakstad, Geir Ø Andersen, Kjetil Sunde, Christofer Lundqvist
Journal: Circulation (2017)

Background: Early prediction of outcome in comatose patients after out-of-hospital cardiac arrest (OHCA) is challenging. So far, recommended prognostication tools consist of clinical examination, b...
Abstract 14808: Bleed Outcomes Following Coronary Artery Stent: Risk Associated With Combined Antithrombotic Therapy Common in Atrial Fibrillation: Insights From Medicare Claims Data
Authors: Gregory A Dadekian, Jeremy Smith, Aaron V Kaplan, Nancy E Morden
Journal: Circulation (2015)

Background: Platelet inhibitor (PI) use following coronary artery stent confers bleed risks, especially for atrial fibrillation (AF) patients on oral anticoagulants (OAC), a subgroup often excluded from randomized stent trials. We studied a national sample of elderly stent recipients to quantify bleed risks associated with combined OAC and PI, pharmacotherapy common in AF. Methods: Using a 40% Medicare random sample denominator file and associated inpatient, outpatient (2003-2012) and prescription (2006-2012) claims, we studied patients age 65 and older receiving a coronary artery stent. We measured OAC and/or prescription PI use after stent placement. Cox regression models estimated risk of bleed events adjusting for individual characteristics, morbidities, and time-varying medication use. Results Overall, 165,718 patients in our sample received a stent, 2006-2012; 20.4% had AF; mean age was 73.8 (SD 6.3). In the first month post-stent, among AF patients, 40.7% received OAC, 85.6% prescription PI, 35.9% both; among non-AF patients corresponding use was 3.5%, 90.3% and 3.1% respectively. At 13 months post stent, 61.0% of AF patients and 71.1% of non-AF patients continued using prescription PIs while 15.5% and 1.7% respectively remained on both PI and OAC therapy. Compared to those taking only prescription PIs, the risk of bleeding associated with warfarin plus PI was 2.05 (95% CI: 1.97 - 2.13); the risk associated with novel OACs (dabigatran or rivaroxaban) plus PIs was 2.60 (95% CI: 2.26 - 2.99). Conclusions: In a national, older population combined OAC and PI use following stent is common in AF patients and associated with bleeding risk. These findings should inform stent selection and antithrombotic strategies. The association between novel OACs and bleeding was unexpected and warrants further exploration as these products gain use.
Hospital admissions (HA) among chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) patients newly treated with enzalutamide (ENZA) or abiraterone (ABI).
Authors: Ruben G.W. Quek, Adrienne M. Gilligan, Shia T. Kent, Christopher Gregory, Neil M. Schultz, Scott Flanders, Bruce A. Brown, Elaine Karol Wong, Arie Barlev
Journal: Journal of Clinical Oncology (2017)

e16524 Background: ENZA and ABI are approved to treat mCRPC in chemotherapy-naïve patients; few real-world analyses exist to compare HA pre- and post-treatment. This study characterized and compared incidence and incidence rate ratios (IRRs) of HA pre/post initiation of ENZA or ABI in chemotherapy-naïve mCRPC patients in the US. Methods: Patients aged ≥ 18 years who initiated ENZA or ABI (2 cohorts) from Jan 2014–Dec 2015 were identified retrospectively from MarketScan® Databases. The index date was the initiation of ENZA or ABI after ≥ 6 months of pre-index continuous health plan enrollment. We identified the top 10 HA incidences using ICD-9/10 CM inpatient claims (separate primary and any position) and assessed pre-/post-index IRRs within each cohort. Generalized estimating equations accounting for within-patient correlation and difference-in-differences regression were fitted to compare IRRs between cohorts. Results: A total of 1603 (ENZA, 656; ABI, 947) patients were included. Mean age was 73 years in both cohorts; mean (standard deviation) Deyo-Charlson Comorbidity Index was 7.9 (2.8) for ENZA and 7.8 (2.9) for ABI; the top 10 HA incidences included cardiac disorder, dyspnea, hypokalemia, liver toxicity, pneumonia, renal impairment, skeletal-related events (any, surgery and fracture) and urinary tract infection. IRRs of HA (any position) due to cardiac disorder, dyspnea, hypokalemia, liver toxicity and pneumonia were significantly higher for post- vs pre-ABI-treated patients (IRR [95% CI]: 1.63 [1.22–2.17], 1.90 [1.21–2.98], 3.13 [1.46–6.71], 2.24 [1.36–3.69] and 2.40 [1.41–4.10]). IRRs of HA (any position) due to cardiac disorder, dyspnea and hypokalemia were significantly lower in the ENZA cohort than ABI cohort (1.02 vs 1.63, 0.84 vs 1.90, 0.65 vs 3.13; all P &lt; 0.05). No statistical significance was observed for any other HA comparisons (primary or any position) between or within ENZA and ABI cohorts. Conclusions: Among chemotherapy-naïve mCRPC patients, significant increases in multiple HA IRRs were observed post- vs pre-ABI treatment, and IRRs were significantly lower for ENZA- vs ABI-treated patients for multiple HA.
Distribution of ETV6-NTRK3 translocations across neoplasms identified from the Mitelman Database.
Authors: Juan Carlos Malpartida, Eric Vick, Noah Hunter Richardson, Kruti Patel, Matthew K Stein, Michael Gary Martin
Journal: Journal of Clinical Oncology (2017)

e23141 Background: Discovered as a novel aberration in congenital fibrosarcoma (CF), the ETV6-NTRK3 translocation (EN) confers oncogenic potential and is inhibited by crizotinib. The present study aims to survey the scope of neoplasms that harbor EN across tumor types. Methods: Utilizing the National Cancer Institute’s Mitelman Database (MD) of Chromosome Aberrations and Gene Fusions patients (pts) were identified with EN and categorized based on tumor type, subtype and incidence. Cancer pts who received tumor profiling with Caris were also surveyed for EN. Results: 47 pts with EN across 12 cancer types were extracted from the MD and had median age of 0.17 years (7 unreported); 38% male; 51% acquired malignancies, 49% congenital; 62% cases were pediatric, 23% adult and 15% unknown. 0/204 pts with Caris tumor profiling were found to have an EN. Cancers with the highest number of EN were: 15 (31.9% EN data set) congenital mesoblastic nephromas (CMN), 10 (21.3%) CF, 7 (14.9%) breast carcinoma (BC; 6 secretory ductal carcinoma (SD) and 1 invasive adenocarcinoma (IA)) and 3 (6.4%) colorectal carcinoma (CRC). EN were found in 8 other malignancies (Table 1). Cancer types with the highest incidence of EN+ cases in the MD were gastrointestinal stromal tumor (GIST; 100%), CMN (75%) and CF (23.3%). Conclusions: These results further our understanding of the distribution of ETV6-NTRK3 translocations in multiple tumor types across the age spectrum and suggest that pts with CMN, CF, BC and CRC requiring high order therapy should be considered for NTRK3-based treatment. [Table: see text]
Serum chitinase activity to predict survival and metastasis of colorectal cancer.
Authors: Zhangfa Song
Journal: Journal of Clinical Oncology (2017)

e15105 Background: In this study we evaluated the role of the chitinase activity (one of the biomarkers) in predicting the liver metastases of colorectal cancer in blood. Methods: The level of chitinase activity were examined in 400 colorectal cancer patients, including 53 synchronous liver metastases in peripheral blood 0.347 colorectal cancer patients peripheral blood was measured before resection of the cancer. The clinical parameters were collected, and the patient were prospectively followed up. Results: The chitinase activity was significantly over-expressed in synchronous liver metastases than colorectal cancer who has no metastases. During the follow up in 347 colorectal cancer patient, higher expression of chitinase activity, higher risk of liver metastases, bothunivariate cox analysis (HR6.0) and multivariate Cox analysis (HR 5.3) show chitinase has high value of predictive the liver metastases after resection of the primary colorectal cancer. Kaplan-Meier analysis shows the chitinase activity has significant correlation to survival in colorectal cancer patients. Moreover, the in vitro study shows the chitinase play important role in cell migration. The metastasis ratio between two groups in non-synchronic colorectal metastasis patients. Conclusions: This study provide experimental evidence that chitinase activity has the potential biomarker for predictive the liver metastases in colorectal cancer. [Table: see text]
Impact of minimal residual disease (MRD) status in clinical outcomes of patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) treated with inotuzumab ozogamicin (InO) in the phase 3 INO-VATE trial.
Authors: Elias Jabbour, Nicola Gökbuget, Anjali S. Advani, Matthias Stelljes, Wendy Stock, Michaela Liedtke, Giovanni Martinelli, Susan Mary O'Brien, Tao Wang, Douglas Laird, Erik Vandendries, Alexander Neuhof, Daniel J. DeAngelo, Hagop M. Kantarjian
Journal: Journal of Clinical Oncology (2018)

7013 Background: MRD negativity is a key prognostic indicator of patient (pt) outcome in ALL and is predictive of improved survival and disease-free status. In the INO-VATE ALL trial (Kantarjian, NEJM 2016), pts with R/R ALL who received InO vs standard chemotherapy (SC) achieved greater remission (CR/CRi; 81% vs 29%) and MRD-negativity (78% vs 28%, in pts with CR/CRi) and had improved overall survival (OS): 7.7 vs 6.7 months. This analysis was conducted to assess prognostic value of MRD negativity by end of treatment (EOT) with InO. Methods: INO-VATE pts who received InO (n = 164) were included. Among pts with CR/CRi, MRD status (by multiparametric flow cytometry at a central lab) was defined as negative (MRD–) if < 1 × 10-4 blasts/nucleated cells (n = 81), or as positive (MRD+; n = 83), based on assessment by EOT. OS, progression-free survival (PFS), and predictors of MRD status (by multivariate logistic regression) are reported from final study data as of Jan 4, 2017. Results: MRD– status with CR/CRi was associated with significantly improved OS and PFS (Table) vs MRD+ status with CR/CRi: unstratified HR 0.512; 1-sided P= 0.0009 for OS and HR 0.423; P< 0.0001 for PFS. Exploratory multivariate analyses indicated that 2nd salvage compared to 1st salvage (OR 0.499, 2-sided P= 0.058) was associated with lower likelihood of having MRD– status, while < 1x109/L absolute circulating blast count at baseline (OR 3.231, P= 0.002) and longer duration of remission (OR 1.033, P= 0.005) were associated with increased likelihood of having MRD– status. Clinical trial information: NCT01564784. Conclusions: Among pts who received InO in the INO-VATE trial, having CR/Cri and MRD– status at EOT was associated with the greatest survival outcomes. However, pts who achieved an MRD+ CR/CRi had much greater survival than those who did not have CR/CRi. In R/R ALL, use of InO may optimize chances to attain the primary goal of complete remission and MRD– status. CR/CRi and MRD– (n = 76) CR/CRi and MRD+* (n = 45) No CR/CRi (n = 43) Median OS, mos [95% CI] 14.1 [8.6–23.0] 7.2 [5.8–10.8] 2.6 [1.9–3.6] Median PFS, mos [95% CI] 8.6 [6.2–11.4] 5.4 [3.9–6.2] 1.4 [1.0–1.9] *includes 6 pts with no MRD assessment