tbuckley/cabot-search huggingface dataset:
TAMing pancreatic cancer: combat with a double edged sword
Authors: Manendra Babu Lankadasari, Pramiti Mukhopadhyay, Sabira Mohammed, Kuzhuvelil B. Harikumar
Journal: Molecular Cancer (2019)

Among all the deadly cancers, pancreatic cancer ranks seventh in mortality. The absence of any grave symptoms coupled with the unavailability of early prognostic and diagnostic markers make the disease incurable in most of the cases. This leads to a late diagnosis, where the disease would have aggravated and thus, incurable. Only around 20% of the cases present the early disease diagnosis. Surgical resection is the prime option available for curative local disease but in the case of advanced cancer, chemotherapy is the standard treatment modality although the patients end up with drug resistance and severe side effects. Desmoplasia plays a very important role in chemoresistance associated with pancreatic cancer and consists of a thick scar tissue around the tumor comprised of different cell populations. The interplay between this heterogenous population in the tumor microenvironment results in sustained tumor growth and metastasis. Accumulating evidences expose the crucial role played by the tumor-associated macrophages in pancreatic cancer and this review briefly presents the origin from their parent lineage and the importance in maintaining tumor hallmarks. Finally we have tried to address their role in imparting chemoresistance and the therapeutic interventions leading to reduced tumor burden.
S1507: Phase II study of docetaxel and trametinib in patients with G12C or non-G12C <i>KRAS</i> mutation positive (+) recurrent non-small cell lung cancer (NSCLC).
Authors: Shirish M. Gadgeel, Jieling Miao, Jonathan W. Riess, Philip C. Mack, Gregory James Gerstner, Timothy F. Burns, Asma Taj, Wallace L. Akerley, Konstantin H. Dragnev, James Moon, David R. Gandara, Karen Kelly
Journal: Journal of Clinical Oncology (2019)

9021 Background: KRAS+ NSCLC remains the most common genetically defined subset of NSCLC. Despite promising pre-clinical data, MEK inhibitors have failed to provide meaningful clinical benefit both as single agents and in combination with chemotherapy in KRAS+ NSCLC patients. Pre-clinical data suggest that efficacy of MEK inhibitors in KRAS+ NSCLC differs based on specific KRAS mutations such as G12C and by status of p53 or LKB1 mutations. We conducted a phase II study to assess the efficacy of docetaxel plus trametinib in KRAS+ NSCLC patients and in specific genetic subsets. Methods: KRAS+ NSCLC patients who had progressive cancer following 1 or 2 prior regimens were eligible. Docetaxel was given at 75 mg/m2 every 3 weeks and trametinib orally at 2 mg daily. The study was 2-stage design to rule out a response rate (RR) of 17% at the 3% level with 90% power if the true rate were 37%. The study required 45 pts with a futility analysis at 30 pts; 13/45 responses would indicate a success. RR was also assessed in G12C and non-G12C cohorts and will be assessed according to presence of co-mutations in p53 and LKB1. Progression free survival (PFS) and overall survival (OS) were secondary endpoints. Multivariate analysis including age, sex, number of prior treatments, prior immunotherapy (IO) and G12C status was conducted. Results: The study enrolled 54 evaluable pts (19 G12C, 9 G12D, 9 G12A); median age 65 years; female 57%; never smokers 7%; adenocarcinoma 89%; liver metastases 31%; 2 prior regimens 70%; prior IO 57%. Outcomes are summarized in Table. Median duration of therapy was 2.2 months and most common toxicities were fatigue (78%), diarrhea (68%), nausea (57%) and vomiting (28%). One patient died of treatment related respiratory failure. There was a trend for worse PFS (HR- 1.86, p = 0.06) and survival (HR- 1.80, p = 0.14) in G12C patients. Analysis of efficacy data according to co-mutations in p53 or LKB1 is ongoing. Conclusions: Docetaxel plus trametinib met the primary endpoint of the study, with a RR of 33% and median survival of 11.1 months in patients with KRAS+ NSCLC, 70% of whom had received 2 prior regimens. Although, there was no statistical difference between KRAS+ subtypes, these data suggest that outcomes may differ between G12C and non-G12C patients. Clinical trial information: NCT02642042. [Table: see text]
Mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients (pts) with platinum-resistant ovarian cancer: Final findings from the FORWARD II study.
Authors: David M. O'Malley, Ursula A. Matulonis, Michael J. Birrer, Cesar Martin Castro, Ignace Vergote, Lainie P. Martin, Gina Mantia-Smaldone, Lucy Gilbert, Antonio González-Martín, Raquel Bratos, Brooke Esteves, Karim S. Malek, Kathleen N. Moore
Journal: Journal of Clinical Oncology (2019)

5520 Background: Mirvetuximab soravtansine is an ADC comprising a FRα-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent. As part of the Phase 1b FORWARD II trial (NCT02606305), the combination of mirvetuximab soravtansine with bevacizumab (BEV) was evaluated in pts with FRα-positive, platinum-resistant ovarian cancer (recurrence within 6 months after last platinum). Methods: Pts received mirvetuximab soravtansine (6 mg/kg; adjusted ideal body weight) and BEV (15 mg/kg) on Day 1 of a 21-day cycle. Responses were assessed according to RECIST 1.1 and adverse events (AEs) evaluated by CTCAE v4.03. Results: In total, 66 pts received combination dosing at this level: 11 during escalation and 55 in expansion. The median age was 63 years, pts received a median of 3 prior lines of systemic therapy (range 1-8), and 62% had received prior therapy with BEV. The most common AEs were diarrhea (58%), nausea (50%), and blurred vision (48%), and were primarily low grade (≤ grade 2). Serious AEs were largely gastrointestinal in nature, with small intestinal obstruction the most frequent individual event (4 pts, 6%). Objective responses were seen in 27 pts for a confirmed overall response rate (ORR) of 41% (95% CI, 29, 54), median progression-free survival (mPFS) interval of 7.1 months (95% CI, 4.9, 9.5), and median duration of response (mDOR) of 8.6 months (95% CI, 4.9, 14.9). In a subset analysis of pts (n = 16) who were bevacizumab-naïve, had 1-2 prior therapies, and medium/high FRα levels (i.e., ≥ 50% of cells with at least moderate staining intensity) the ORR was 56% (95% CI, 30, 80), mPFS 9.9 months (95% CI, 4.1, 15.9), and mDOR 12 months (95% CI, 6.0, 14.9). Conclusions: The combination of mirvetuximab soravtansine with BEV exhibits favorable tolerability in pts with platinum-resistant ovarian cancer, characterized by a manageable side-effect profile. The encouraging efficacy compares favorably to reported outcomes for BEV and chemotherapy seen in similar patient populations. These data support continued exploration of the combination in ovarian cancer. Clinical trial information: NCT02606305.
Evaluating use of interpreters in educating immigrants on cancer prevention and screening guidelines.
Authors: Linda Bulone, Beatriz Korc-Grodzicki, Natalie Gangai, Ruth Manna, Rosario Costas-Muñiz, Margaret Kemeny
Journal: Journal of Clinical Oncology (2019)

e18149 Background: Community outreach is commonly used to disseminate cancer prevention &amp; screening guidelines (CPSG). Minority, immigrant populations with language barriers tend to be excluded from these activities due to the lack of bilingual professionals available to deliver this education. This program was aimed to test whether CPSG education improves knowledge after being taught by an English-speaking medical professional and nonmedical, community-based interpreters working in South Asian and Hispanic communities in New York City (NYC). Methods: Team members from two cancer centers and community-based minority organizations in NYC partnered to create and deliver programs on CPSG to linguistically diverse communities by an English-speaking medical professional utilizing community-based interpreters. Participant knowledge was assessed using matched pre-post surveys in participants’ respective languages. Behavioral intention was measured using a Likert scale from 1-4 with anchors at 1) “Will not do it” and 4) “Already have/doing it”. Paired t-tests were used to compare pre to post mean score and a p-value &lt; 0.05 was considered statistically significant. Behavioral intention rated positively if participants endorsed “will do it” or “already doing” the healthy behavior. Results: 188 community dwelling adults participated in 5 educational sessions, 122 completing pre and post assessments. Median age was 68, two thirds (69%) were female. 94% were born outside of the US, coming from 12 different countries, speaking 6 different primary languages. Knowledge increased from an average of 33% correct responses pre-session to 63% correct post-session – a statistically significant change ( t (121) = -10.58, p &lt; .001). Behavioral intention scores reveal 83-96% participants reporting they will continue to or plan to seek screening and screening information from their doctors as well as make lifestyle changes related to decreasing their cancer risk. Conclusions: This program demonstrates CPSG can not only be taught in English with use of interpreters, but can be successfully received by immigrant community participants who historically may not have these programs available to them due to language barriers.
Suppression of testosterone production using abiraterone acetate (AA) with or without androgen deprivation therapy (ADT) in metastatic castration resistant prostate cancer (mCRPC).
Authors: Gautam Gopalji Jha, Engle Jeff
Journal: Journal of Clinical Oncology (2019)

5049 Background: Patients with metastatic prostate cancer (mPC) are treated with lifelong ADT even after progression and every treatment for mPC has been tested only in the setting of androgen deprivation. Androgen synthesis inhibitor AA which inhibits synthesis of androgen that later get converted to testosterone has been studied and approved only alongside ADT similar to all other agents that have no or limited activity on testosterone suppression. We reviewed the ability of AA to sufficiently suppress testosterone levels as compared to AA plus ADT and its potential impact on cost savings. Methods: This retrospective study included consecutive patients with mCRPC treated with AA alone or in combination with ADT (in absence of orchiectomy) who had been followed with serial testosterone values on therapy. A cost analysis was performed to determine the cost avoidance by omitting leuprolide injections while on AA. The cost avoidance was calculated by multiplying the total number of injections by the wholesale acquisition cost of $5252.86 for a three month leuprolide injection. Results: Of 57 patients included in the final analysis, 36 received AA plus ADT, 10 received AA alone, and 11 started off with AA plus ADT before transitioning to AA alone. Testosterone levels were drawn 235 times. Testosterone was undetectable (below &lt; 2 ng/dl) in both arms, 134 of 152 in combination arm and 86 of 99 in the AA alone arm. The median testosterone concentration when detectable was 3 ng/dL in AA alone and 3.5 ng/dL in AA plus ADT. None in the combination arm and only one testosterone value in AA arm had testosterone &gt; than 30 ng/dl. The mean duration of AA use in this study was close to one year, and the total duration of therapy was approximately 61 years which could result in elimination of 244 leuprolide administrations and approximately $1.29 million in total cost savings. Conclusions: AA alone is able to effectively suppress testosterone synthesis in patients with prostate cancer. ADT with GnRH agonist or antagonist can be safely withheld while on therapy with AA and testosterone values followed to confirm adequate androgen suppression. This has acquired new significance after studies in patients with hormone sensitive disease where median duration of treatment was 33 months which could translate to an avoidable expense of $55.5 million for 960 patients in ‘STAMPEDE’ study and $34.5 million in ‘LATITUDE’ study from leuprolide administration in combination arm.
Abstract 15612: The Effect of Right Ventricular Volume Overload on Ventricular Deformation - Differential Response in Patients with Atrial Septal Defect and after Tetralogy of Fallot Repair.
Authors: Andreea Dragulescu, Lars Grosse-Wortmann, Luc Mertens
Journal: Circulation (2011)

Background: Right ventricular (RV) volume overload results in RV dilatation. RV strain (S) and strain rate (SR) imaging allow a quantitative assessment of RV function which is influenced by RV geom...
Novel anti-EGFRvIII bispecific T cell engager (BiTE) antibody construct in glioblastoma (GBM): Trial in progress of AMG 596 in patients with recurrent or newly diagnosed disease.
Authors: Mark Rosenthal, Carmen Balana, Myra Ellen Van Linde, Cyrus Sayehli, Walter M. Fiedler, Martin Wermke, Christophe Massard, Agnes Ang, Johannes Kast, Sabine Stienen, Timothy Francis Cloughesy
Journal: Journal of Clinical Oncology (2019)

TPS2071 Background: GBM is the most aggressive primary brain tumor in adults and is extremely difficult to treat. Patients with GBM tend to progress rapidly within weeks or months. Median overall survival is only 12–15 months despite aggressive treatment, and less than 5% of patients survive 5 years. GBM also severely impacts quality of life and cognitive function. Approximately 50% of GBM tumors test positive for amplification or mutation of the epidermal growth factor receptor (EGFR), the most common of which is the EGFRvIII gain-of-function mutation. AMG 596 is a bispecific T cell engager (BiTE®) antibody construct designed to crosslink and engage CD3-positive T cells to EGFRvIII-positive tumor cells, inducing tumor cell lysis and T cell proliferation. A clinical trial is being conducted for this novel immunotherapy agent in patients with EGFRvIII-positive GBM. Methods: NCT03296696 is a phase 1, first-in-human, open-label, sequential dose-escalation and dose-expansion study evaluating the safety, tolerability, and pharmacokinetics and pharmacodynamics (PK/PD) of AMG 596 in patients with EGFRvIII-positive GBM. AMG 596 is administered via continuous intravenous infusion. The study is expected to enroll approximately 82 patients total and comprises two groups (Group 1: patients with recurrent GBM; Group 2: patients with newly diagnosed GBM in the maintenance treatment phase after standard of care). Key inclusion criteria include: male or female; ≥ 18 years of age; with pathologically documented and diagnosed grade IV GBM; Eastern Cooperative Oncology Group performance status ≤ 1; life expectancy ≥ 3 months per study investigator; and acceptable renal, hematological, and hepatic function. The primary endpoint evaluates the safety and tolerability of AMG 596 via collection of treatment-emergent adverse events. Additional endpoints include objective response rate per modified Response Assessment in Neuro-Oncology Criteria and PK/PD analyses of AMG 596 in serum. The study began enrolling patients in April 2018 and enrollment is ongoing. For more information, please contact Amgen Medical Information: medinfo@amgen.com. Clinical trial information: NCT03296696.
Unveiling the real-world outcomes of breast cancer (BC) patients with taxanes-induced neuropathy using a digital patient-powered network (PPN).
Authors: Raanan Berger, Lior Hasid, Irad Deutsch, Eliran Malki, Maytal Bivas-Benita
Journal: Journal of Clinical Oncology (2019)

e18248 Background: Taxanes-induced neuropathy is common in BC patients receiving taxanes, forcing dose reductions and treatment delays and posing serious challenges for the long-term patient QoL. Discovering neuropathy predictors in patients could guide better treatment decisions, improved QoL and reduce healthcare costs. Belong digital PPN is a social network for cancer patients and caregivers that supports disease management. In this study we used our artificial intelligence (AI) engine to classify the prevalence, characteristics and taxanes-induced neuropathy status of BC patients. Methods: We analyzed real-world patient-reported outcomes provided voluntarily and anonymously from users on the Belong PPN. Data from BC patients reporting treatment with taxanes was extracted and additional analysis segmented the data to those who experienced neuropathy and those who did not. Further validation of the data was performed by our research team to assure accuracy. Results: We evaluated 169 BC cancer patients from the US treated with taxanes. In the cohort 72% were Paclitaxel-treated and 28% Docetaxel-treated at various disease stages: 68% at early stage BC (0-2) and 32% at the advanced/metastatic stages (3-4). 83% of Paclitaxel-treated patients and 67% of Docetaxel-treated patients reported experiencing neuropathy in the Belong platform. These real-world reports indicated significantly higher incidence of taxane-induced neuropathy in comparison to literature summarizing data from clinical trials, suggesting neuropathy incidence of 27% for paclitaxel and 16% for docetaxel (grades 2-4). Conclusions: Real-world patient-reported outcomes from the Belong PPN captured the prevalence of taxanes-induced neuropathy in BC patients and correlated it to the specific drug in use. Evidence for higher incidence of taxanes-induced neuropathy may lead to lower patient QoL and higher healthcare costs and should stimulate better treatment decisions. Further exploration of the gap between controlled clinical studies and real-world evidence is urgently needed to understand the true patient outcomes and optimize healthcare accordingly.
HOUT-13. POSTOPERATIVE HEARING PRESERVATION IN PATIENTS UNDERGOING RETROSIGMOID CRANIOTOMY FOR RESECTION OF VESTIBULAR SCHWANNOMAS: A META-ANALYSIS OF 1,249 PATIENTS
Authors: Methma Udawatta, Vera Ong, John Sheppard, Courtney Duong, Thien Nguyen, Isabelle Kwan, Komal Preet, Quinton Gopen, Isaac Yang
Journal: Neuro-Oncology (2018)

Vestibular schwannomas (VS) are slow-growing, benign tumors originating from over-proliferation of Schwann cells ensheathing the vestibulocochlear nerve. Sensorineuronal hearing loss is the most common presenting symptom. RESEARCH QUESTION: To investigate estimated hearing preservation (HP) rates in VS patients after retrosigmoid (RS) surgery through a meta-analysis based on published hearing outcomes. PubMed and Cochrane were used to identify applicable retrospective and prospective studies. Study heterogeneity was quantified through t2, Q, and I2 statistics. A Wald-type Q statistic was used to assess statistical significance of study heterogeneity. Assessment of study bias was performed using standard funnel plot analysis and an Eggers test for funnel plot asymmetry. Significant cross-study heterogeneity was found, with rates of HP ranging from 12–79% across studies. Aggregate HP was 23% under a fixed effects model and 37% under random study effects. Clear systematic bias was also apparent, with disproportionate numbers of studies reporting HP rates markedly higher than the aggregate estimates (P< 0.0001). As expected, rates of HP were also strongly dependent on preoperative tumor size, with rates of 59%, 37%, and 11% observed for intracanalicular, small, and large (>20 mm) tumors, respectively. SIGNIFICANCE: HP rates are likely dependent on multiple factors, with tumor size as a strong effect. It is critical to discuss the patients expectations for HP when deciding treatment plans for VS.
First subsequent treatment after discontinuation of durvalumab in unresectable, stage III NSCLC patients from PACIFIC.
Authors: David Planchard, Byoung Chul Cho, Jhanelle Elaine Gray, Luis G. Paz-Ares, Mustafa Ozguroglu, Augusto E. Villegas, Davey B. Daniel, David Vicente, Shuji Murakami, Rina Hui, Takayasu Kurata, Alberto Chiappori, Ki Hyeong Lee, Maike De Wit, Yu Gu, Catherine Wadsworth, Phillip A. Dennis, Scott Joseph Antonia
Journal: Journal of Clinical Oncology (2019)

9054 Background: In the phase 3 PACIFIC trial of unresectable, stage III NSCLC patients (pts) without progression after concurrent chemoradiotherapy (cCRT), durvalumab (durva) significantly improved PFS and OS with similar safety compared to placebo (pbo). We performed exploratory analyses to characterize first subsequent treatment (Tx) after discontinuation of durva. Methods: Pts with WHO PS 0/1 and any tumor PD-L1 status were randomized (2:1) 1–42 days after ≥2 cycles of platinum-based cCRT to durva 10 mg/kg IV or pbo Q2W up to 12 months, stratified by age, sex and smoking history. Pts were classified by the use or not of first subsequent Tx and category of first systemic Tx (platinum doublet CT [PDCT], single-agent CT [SCT], immunotherapy [IT] or targeted therapy [TT]). Results: As of Mar 22, 2018, 216/476 (45.4%) and 153/237 (64.6%) in the durva and pbo arms, respectively, had a RECIST-based PFS event per BICR (5.7% and 8.4% due to death). 195 (41.0%) and 128 (54.0%) received first subsequent Tx, most of which were systemic Tx (158 [33.2%] and 109 [46.0%]): PDCT (16.4% and 19.0%), SCT (8.6% and 8.4%), IT (4.2% and 13.5%) or TT (3.8% and 5.1%); 7.8% and 8.0% received RT only. Time to first subsequent therapy or death (TFST) was longer with durva vs pbo (HR 0.58; 95% CI 0.47–0.72; median 21.0 vs 10.4 months). Baseline characteristics of pts with or without first subsequent Tx were similar, and similar across durva or pbo arms. Among pts with systemic Tx, baseline characteristics (including pre-cCRT PD-L1 status) were generally similar, except pts on TT, more of whom were EGFR+ (70.0% vs 0–6.6% of other systemic Tx groups) with commonly associated phenotypes (more females, Asians, non-smokers and non-squamous pts). Best overall response to first systemic Tx will be presented. Conclusions: Due to longer PFS and fewer progression events with durva vs pbo, fewer pts on durva required subsequent Tx and, per TFST, much later. With the exception of IT, use of each subsequent Tx was similar between the durva and pbo arms with PDCT the most common. Baseline characteristics were similar for pts with or without first subsequent Tx and pts who received first systemic Tx, except for pts who received TT, as expected due to their molecular profile.
Prevalence of food challenge: confirmed food allergies in a large pediatric population based study in Melbourne, Australia
Authors: N. Osborne, L. Gurrin, J. Koplin, P. Martin, M. Robinson, M. Slaa, L. Thiele, L. Miles, D. Dawson, T. Dang, D. Hill, A. Lowe, M. Matheson, A. Ponsonby, M. Tang, M. Wake, S. Dharmage, K. Allen
Journal: Allergy (2010)