tbuckley/cabot-search huggingface dataset:
Cost-effectiveness for metastatic colorectal cancer.
Authors: Linli Yao, Jiaqi Han, Longjiang She, Dong Ding, Mengting Liao, Huabin Hu, Shan Zeng, Liangfang Shen, Jin Huang
Journal: Journal of Clinical Oncology (2019)

e15003 Background: As standard third-line treatments for metastatic colorectal cancer, regorafenib and fruquintinib, compared with placebo, increase median overall survival by 2.5 months and 2.7 months, respectively. Given the incremental clinical benefit, we aim to estimate the cost effectiveness of regorafenib versus fruquintinib in the third-line treatment for patients with metastatic colorectal cancer from Chinese payer perspective. Methods: A mathematical Markov model was established to project the cost-effectiveness of regorafenib versus fruquintinib from the CONCUR and FRESCO clinical trials. Quality-adjusted-life-years (QALYs) were analyzed with extracted data from the trials. Willingness to pay (WTP) of $26508 was used. Drug costs were estimated from the perspectives of the health care system in the People’s Republic of China. One way sensitivity and scenario analyses were performed by varying potentially modifiable parameters of the model. Results: Fruquintinib, compared with regorafenib, provided an additional 0.028 QALYs (0.274 QALYs versus 0.246 QALYs) at less cost ($33536 versus $35607). Conclusions: Fruquintinib is more cost-effective than regorafenib as the third-line management for patients with metastatic colorectal cancer when WTP is $26508.
Retrospective review for outcomes of IDH mutant, 1p/19q co-deleted gliomas based on initial treatment.
Authors: Christopher Ray Trevino, Shiao-Pei S. Weathers, Kristin Alfaro-Munoz, Gemma Hallatt, Garret L. Wiliford, Minjeong Park, Diane D. Liu, Tim Overeen, Jacob Joseph Mandel, John Frederick De Groot
Journal: Journal of Clinical Oncology (2019)

2063 Background: Treatment for oligodendroglioma in the molecular era is based on trials that used histologic criteria alone and has evolved over time to include observation and a combination of radiation (RT) and chemotherapy. In particular, treatment for high-risk patients is variable including sequential RT followed by temozolomide (TMZ) or procarbazine, lomustine, and vincristine (PCV) or chemoradiation with TMZ. This is a single institutional review of outcomes of molecular IDH mutant, 1p19q co-deleted oligodendroglioma based on initial treatment. Methods: Using both Palantir Foundry and direct record review, we stratified adult patients with grade II/III gliomas diagnosed from 1997-2017 harboring an IDH mutation and 1p/19q co-deletion based on initial treatment and excluded patients without molecular testing. Overall survival (OS) and progression free survival (PFS) were calculated by Kaplan-Meier analysis. Results: 187 patients were initially managed as: 55 (31%) observation, 16 (9%) RT alone, 51 (29%) chemotherapy alone, 39 (22%) sequential RT and chemotherapy, and 17 (10%) chemoradiation. For all patients, a subtotal (STR) or gross total resection (GTR) was associated with prolonged OS vs biopsy (NR vs 123 mos, p = 0.007). Age &lt; 40 did not correlate with OS (p = 0.87). In the chemotherapy group, although PCV demonstrated improved PFS vs TMZ (157 vs 45 mos, p = 0.004) there was no difference in OS, only 3 patients received PCV. For patients treated sequentially with RT and PCV or TMZ vs chemoradiation, there were no differences in OS (NR vs 140 mos; p = 0.87) or PFS (49 vs 45 mos, p = 0.52), though sequential treatment trended toward prolonged survival. Conclusions: This data supports both STR and GTR as prognostic for overall survival. Despite the prolonged PFS observed with patients treated with PCV alone which did not translate to improved OS, the small PCV sample size limits the strength of this evidence. We did not find significant survival differences between sequential RT and chemotherapy vs concurrent, but interestingly, there was a trend toward improved OS in sequentially treated patients.
Diverse RB1 mutations and co-occurring molecular alterations in advanced NSCLC.
Authors: Jie Huang, Lun-Xi Peng, Jin-Ji Yang, Yi-Long Wu
Journal: Journal of Clinical Oncology (2019)

e20672 Background: Retinoblastoma transcriptional corepressor 1 (RB1) mutation is strikingly more frequent in non-small cell lung cancer (NSCLC) with SCLC transformation (SCLC-T) than that remain NSCLC. However, NSCLC patients harboring RB1 mutations do not necessarily transform to SCLC. Thus, exploring RB1 mutation frequency and co-occurring genomic alterations is potentially important to understand the SCLC-T mechanism. Methods: We investigated 47 NSCLC pts with RB1 aberrations at our institution. Submitted samples (tissue, plasma, cerebrospinal fluid and pleural effusion) were analyzed using next-generation sequencing across at least 139 genes (139-520). Demographics, molecular features and outcomes were analyzed. Results: Among 47 pts (27F/20M), median age was 58. Twenty (47%) had brain metastases and 7 (15%) underwent SCLC-T. A total of 39 types of RB1 mutations were identified, in which copy number deletion is the most common (40%). RB1 mutations were present from early NSCLC and were detected in 88%(29/33), 82%(9/11), 70%(9/13) and 42% (20/48) of tissue, pleural effusion, CSF and plasma samples, respectively. The most frequent co-occurring alterations were TP53 (100%, 95%) and EGFR (100%, 93%) in both SCLC-T group and non-transformed group. Besides, mutations involving in the PI3K pathway were often detected: PIK3CA (57%, 20%), AKT (43%, 10%), PTEN (14%, 15%), MET (14%, 15%), NTRK1 (14%, 13%). Notably, RB1 also co-occurred with ALK fusion (1/47). Moreover, SCLC-T group harbored significant higher frequency of RB1 mutation compared with non-transformed group. Conclusions: RB1 mutations in NSCLC are associated with a trend toward SCLC-T, and the mechanisms may be increased frequency of RB1 mutations and co-occurring similar molecular alterations to those in SCLC.
Correlation between K-RAS mutant subsets, TP53 mutation, and PD-L1 status in non-small cell lung cancer (NSCLC).
Authors: Nagla Fawzy Abdel Karim, Chisom Onuoha, Imran Ahmad, Ihab Eldessouki, Patrick C. Ma, Rebecca Feldman, Hirva Mamdani, David Craig Portnoy, Alexander I. Spira, Stephen V. Liu, Abdul Rafeh Naqash
Journal: Journal of Clinical Oncology (2019)

e14272 Background: K-RAS is a non-targetable mutation with no established predictive value. However, PD-L1 is the only approved predictive marker for immunotherapy in NSCLC. K-RAS mutation like PD-L1 has been associated with smoking. TP53 and K-RAS mutations have been identified in aggressive neoplasms. We hypothesized that K-RAS mutant NSCLC has higher PD-L1 expression suggestive of improved response to immunotherapy. Methods: The Caris database from 2016 - 2018 was queried and patients with NSCLC were identified. ≥1% staining for PD-L1 (22c3 antibody) was considered positive. PD-L1 expression as well as K-RAS and TP53 mutation status were analyzed and correlation between different variables were identified using ANOVA. Results: We identified 8,471 patients with NSCLC, where 66% had TP53 mutation and 26.9% had K-RAS mutation; both mutations were identified in 12% of the patients. In the subset of combined K-RAS and TP53 mutations there were 71.48% having positive PD-L1 expression with female predominance 1.4:1. Of the eight main K-RAS mutation subsets, G12C subset was the most common. Compared to other K-RAS subtypes, G12C was associated with the higher occurrence of PD-L1 positivity (62.68%,p &lt; 0.04; Table). Conclusions: In comparison to other subsets of K-RAS mutation, G12C had the highest occurrence of PD-L1 expression, suggestive of improved response to immunotherapy. However, the subset of patients with combined K-RAS and TP53 mutations had a higher occurrence for the PD-L1 positive status of 71.48%. [Table: see text]
Evaluation of Electronic Activity Monitors (EAMs) during phase I clinical trials.
Authors: Mariana Scaranti, Raghav Sundar, Robert Daly, Dearbhaile Catherine Collins, David Dolling, Spyridon Gennatas, Bindumalini Rao Baikady, Stan B Kaye, Udai Banerji, Juanita Suzanne Lopez, Johann S. De Bono, Anna Rachel Minchom
Journal: Journal of Clinical Oncology (2019)

e18175 Background: EAMs are wearable devices that record aspects of activity, including heart rate and step count. Medical oncologists use performance status (PS) (such as ECOG and Karnofsky) to assess patient’s physical function and to aid treatment decisions. These are subject to patient and physician bias. Our study evaluated the use of EAMs (Fitbit ®) during phase I trials, correlating EAM indices with PS and patient outcomes. Methods: We recruited patients in an academic hospital Drug Development Unit. Patients participating in a phase I trial consented to wear an EAM prior to starting and during the first treatment cycle. Physicians assessed PS at 4 timepoints. Outcomes (progression free survival (PFS), overall survival (OS), adverse events) were recorded. Results: Twenty-five patients were enrolled. At the time of data analysis results were available for 16 patients. Patients wore the EAM for an average of 70.3% (standard deviation 21%) of their time on study, defined as time with recordable heart rate. Mean step count per day varied with ECOG PS although the correlation did not reach statistical significance (co-efficient -1611.1 steps for each change in ECOG PS, p = 0.07, mixed effect regression model). A higher mean step count/day correlated with longer OS (HR0.67, p = 0.01, Cox proportional hazard model). Physician-assessed PS did not correlate with OS (HR2.65, p = 0.37, Cox proportional hazard model). There was no correlation between mean step count and PFS (HR1.7, p = 0.39, Cox proportional hazard model). Conclusions: The use of EAMs is feasible in this patient group. A higher step count correlated with longer OS whereas physician-assessed PS did not. Further research into the potential of EAMs as a means of predicting patient survival to guide decisions on eligibility for phase I trials and the potential for devising a revised Royal Marsden prognostic score incorporating EAM indices is warranted. Clinical trial information: SE536. [Table: see text]
Plinabulin (Plin) combined with half-dose pegfilgrastim (Peg) compared with full-dose peg alone for chemotherapy- induced-neutropenia (CIN): Neutrophil, bone pain, and immunosuppressive effects.
Authors: Douglas W. Blayney, Stephan Ogenstad, Yuankai Shi, Qingyuan Zhang, Jifeng Feng, Tao Sun, Lihua Du, Lan Huang, Ramon Mohanlal
Journal: Journal of Clinical Oncology (2019)

e12017 Background: Peg is used for CIN prevention. Plin, a novel, non-G-CSF agent is in Phase (Ph) 3 trials for CIN prevention and as an anticancer (NSCLC) agent. In contrast to Peg, Plin does not cause bone pain and maintains absolute neutrophil counts (ANC) within the normal range. Furthermore, Peg, but not Plin, increases Neutrophil-to-Lymphocyte Ratio (NLR) and Lymphocyte-to-Monocyte Ratio (LMR) to immune suppressive values; i.e. NLR&gt;5 and LMR&lt;3.2 (Blayney, ASCO 2018, ESMO 2018, ASCO-SITC 2018). We tested the effects on CIN, bone pain and immune-suppressive profile (i.e. NLR&gt; 5 and LMR&lt;3.2), comparing Plin+half Peg dose to full dose Peg alone (the current CIN standard of care). Methods: Early stage Breast Cancer patients (pts) received high febrile neutropenia (FN) risk TAC (docetaxel, doxorubicin, cyclophosphamide) and either full dose Peg 6 mg (Peg6; n=22) or Peg 3 mg (half dose) + Plin 20 mg/m2 (Peg3/Plin; n = 21) in a Ph 2 trial (NCT03294577). Peg was given ~24 hrs after TAC, and Plin ~30 min after TAC. Blood was drawn for ANC, NLR, MLR daily on Day (D) 0 to D15 in cycle 1. Validated bone pain assessments were done at predose D1, 2,3,4,6,7 and 8 in cycle 1. NLR and LMR were calculated from D6 on (ANC effects with Peg or Plin occur after D6). Results: Grade 4 and Grade 3/4 Neutropenia occurred in 59.1% and 81.2% of pts in the Peg6 arm vs 52.4% and 57.1% in the Peg3/Plin arm. Peg3/Plin was well-tolerated and non-inferior to Peg6 for duration of severe neutropenia (P&lt;0.05). FN occurred in 1 pt each in Peg6 and Peg3/Plin. Bone pain with Peg3/Plin was less vs Peg6: frequency of pts with at least 1,3 or 5 days of bone pain was 90.9%, 36.7% and 18.2 % with Peg6, whereas 33.3%, 14.3% and 4.76% with Peg3/Plin (p&lt;0.0001 for at least 1 day). Frequency of NLR≥5 and LMR≤3.2 was higher with Peg6 vs Peg3/Plin (p&lt;0.045 to P&lt;0.0004 between D8 to D15). Clinical trial information: NCT03294577. Conclusions: Half dose Peg combined with Plin is equally effective against CIN as full dose Peg, but with much less bone pain and immune-suppressive potential.[Table: see text]
Reporting of patient reported outcome (PRO) in clinical trials: A systematic review of clinical trials.
Authors: Liat Vidal-Fisher, Laura Vidal Boixader, Vasily Andrianov, Kelly Kevelin Curtis, Daniel Shepshelovich, Keren Rachel Moss
Journal: Journal of Clinical Oncology (2019)

6590 Background: Clinically relevant outcomes as improvements in overall survival (OS) or quality of life (QOL) should guide decision-making. The FDA encourages the implementation of patient-centric measures in clinical trials. Over the past decade a growing number of protocols have included PROs in their outcome measures. We aimed to evaluate the frequency at which PRO measures, incorporated into clinical trials, are made publicly available, when trial results are published. Methods: We searched Citeline Trialtrove database, a registry of clinical trials, for randomized phase 3 trials of patients with non-small cell lung cancer (NSCLC), recruiting during 2006-2016, with PRO listed. We excluded trials evaluating supportive treatment, and those unpublished. We identified publications associated with the trial, and extracted various parameters, including whether or not PRO outcome was published. Results: Of 158 NSCLC trials identified, 99 listed at least 1 PRO. 24 trials were excluded (supportive care, unpublished). The commonly used scales were EORTC-QLQ C30, QLQ-LC13, LCSS, FACT-L, and EQ-5D. Study sponsor was industry in 45 trials, and industry-academic in 12 trials. Of 75 trials analyzed, 41 (55%) published the results of the PRO endpoint. Only 37% of the 75 included a comprehensive report of PRO, and many publications referenced the PRO briefly. Of 41 trials that reported PRO, only 21 (51%) provided information about missing PRO data. 59 trials were published as full-text, of which 40 (68%) reported the PRO, and 53% reported the PRO more than 6 months after the initial full publication. Of the trials that showed PFS benefit, with no OS benefit, 22/34 (65%) published the results of the PRO endpoints. Conclusions: Despite a growing emphasis on QOL and the inclusion of PROs in oncology clinical trials, and despite patient and healthcare provider efforts to record PRO data, a significant number of NSCLC randomized trials do not report the PRO. The collection of PRO data should result in routine, timely and appropriate reporting as part of the trial outcome publication, to allow for a thorough assessment of investigational clinically relevant treatment effect.
AB0589 ANCA ASSOCIATED VASCULITIS: OUR EXPERIENCE FROM A TERITIARY CARE CENTER OVER 10 YEARS
Authors: Anjani Gummadi, Ankita Singh, Sandesh Guleria, Pandiarajan Vignesh, Anju Gupta, Deepti Suri, Ankur Jindal, Biman Saikia, Amit Rawat, Surjit Singh
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> The anti-neutrophil cytoplasmic antibody (ANCA)- associated vasculitides (AAV) are a group of disorders characterized by necrotizing inflammation of the small to medium vessels in association with autoantibodies. Childhood ANCA vasculitides are rare but can cause organ or even life-threatening systemic vasculitis. Children most frequently present with rapidly evolving, severe disease. <h3>Objectives:</h3> To describe the clinical spectrum of ANCA associated vasculitis, the treatment given and follow up <h3>Methods:</h3> A single-centre retrospective analysis of ANCA associated vasculitis over a period of 10 years from 2008 to 2018 <h3>Results:</h3> Six children (2 boys; 4 girls) were diagnosed to have AAV during this period. Median age at diagnosis was 11.25 years (range 8-18 years). Median delay in diagnosis was 1.5 months (range 1-8 months). Presenting clinical features included lung disease- 4 children; arthritis- 3 (knee, right ankle-left 3<sup>rd</sup> MCP, left elbow-knee) hemoptysis- 2 children; ear discharge- 1; redness of eye-1; oliguria, gross hematuria-2; anasarca-2; 2 children had concomitant neurological symptoms (left foot drop, quadriparesis with seizures). All children had fever at presentation. Laboratory investigations showed elevated erthrocyte sedimentation rate(ESR) and C-reactive protein(CRP). ANCA testing was positive in 6 children (3 c-ANCA, +PR3, 3 p-ANCA, +MPO). Deranged renal function tests, proteinuria, microscopic hematuria) were seen in 4 out of 6 children. Renal biopsy showed pauci immune glomerulonephritis in 4 cases who presented with nephritis. All patients were treated with 5 pulses of intravenous methylprednisolone(30 mg/kg/day) with tapering doses of oral steroids. Intravenous cyclophosphamide pulses was given in 5 children while 1 received additional plasmapheresis (PLEX)- 8 cycles. Mintainence therapy included azathioprine(given in 5 children), low-dose prednisolone. Thrombocytopenia was noted in 1 child while on azathioprine; this was subsequently substituted with mycophenolate mofetil. Two children have been lost to follow-up. Median duration of follow-up is 35.5 months (range 8-124 months). All 4 children have attained remission with good compliance and there are no relapses. <h3>Conclusion:</h3> While an evidence base treatment of AAV in children is limited, our data suggests that prolonged remission can be achieved with aggressive immnosupressive therapy, however prognosis of childhood AAV remains guarded. <h3>Disclosure of Interests:</h3> None declared
Association of medication (Med) and antibiotic (Abx) use with response and survival in advanced melanoma (MEL) receiving PD-1 inhibitors.
Authors: Amit Hemadri, Huang Lin, Yan Lin, Amy Rose, Cindy Sander, Yana Najjar, Hassane M. Zarour, John M. Kirkwood, Diwakar Davar
Journal: Journal of Clinical Oncology (2019)

9572 Background: Retrospective studies suggest that various med could dichotomous effects in regards to immunotherapy. These include adverse (antibiotics) and positive (aspirin, beta-blockers) influences. To evaluate potential additive or detrimental effects of various med in patients (pts) receiving PD-1 immunotherapy, we performed a retrospective evaluation of med intake in 172 pts with stage IV cutaneous MEL focusing on aspirin (asp), antacid (ant), antibiotic (abx), bisphosphonate (bisp), metformin (met) and statin (stat) intake. Methods: Pts with stage IV cutaneous MEL who received anti PD-1 therapy at the University of Pittsburgh between 2014-2018 were included in this analysis. PD-1 blockade was continued until progression or intolerable toxicity. Tumor assessment was performed at baseline and every 12 weeks and response classified per RECIST v1.1. Clinical and demographic data were obtained. Med intake was documented based on chart review in all pts. Intake was confirmed by analyzing at least one other note from a non-oncological provider. Descriptive statistics were created for all covariates. Kaplan Meier and Cox proportional hazard regression were performed to assess how categorical variables related to response (ORR), overall survival (OS) and progression free survival (PFS) measured in months (mths). Results: 172 pts with advanced MEL were evaluated. Asp, ant, abx, bisp, met and stat use was documented in 62, 82, 29, 4, 15 and 57 pts respectively. ORR was not significantly related to intake of asp, ant, bisp, met and stat use; although ORR was lower in pts who received abx (p=0.0328). There was no significant difference in PFS and OS in pts who received asp, ant, bisp, met and stat. In patients who received abx compared to those who did not, median PFS (16.6 mths vs. 19.8 mths) and median OS (23.8 mths vs. 35.4) were both lower. Abx use did not interact with other meds. Conclusions: In this retrospective series of advanced MEL pts treated with PD-1 blockade, abx use was adversely associated with response to PD-1 blockade. Abx use was also associated with poorer PFS and OS. Conversely, neither a positive nor negative association with ORR, PFS and/or OS was seen with asp, ant, bisp, met and stat use. These results validate prior studies suggesting that abx use is associated with worse outcomes in pts receiving PD-1 blockade possibly by mediating intestinal dysbiosis.
Neoadjuvant nivolumab (N) or nivolumab plus ipilimumab (NI) for resectable non-small cell lung cancer (NSCLC): Clinical and correlative results from the NEOSTAR study.
Authors: Tina Cascone, William Nassib William, Annikka Weissferdt, Heather Y. Lin, Cheuk Hong Leung, Brett W. Carter, Frank V. Fossella, Frank Mott, Vassiliki Papadimitrakopoulou, George R. Blumenschein, Xiuning Le, Lorenzo Federico, Edwin Roger Parra Cuentas, Chantale Bernatchez, Ignacio Ivan Wistuba, Ara A. Vaporciyan, Don Lynn Gibbons, Stephen Swisher, John Heymach, Boris Sepesi
Journal: Journal of Clinical Oncology (2019)

8504 Background: Neoadjuvant immune checkpoint inhibitors (ICIs) induce major pathologic response (MPR) rates of 20 to 45% in resected NSCLCs. We report the results of NEOSTAR - a phase 2 trial of neoadjuvant N or NI for NSCLCs. Methods: Pts with stage I-IIIA (single N2) resectable NSCLC (AJCC 7 th ), PS 0-1, were randomized to N (3 mg/kg IV, D1, 15, 29) or N plus I (1 mg/kg IV, D1) followed by surgery (n = 44). Primary endpoint: MPR (≤10% viable tumor), hypothesized to be higher than MPR to induction chemotherapy historical controls. Tumor immune infiltrates and pre- &amp; post-ICI tumor PD-L1 % were assessed by flow cytometry &amp; IHC. Wilcoxon ranked sum test &amp; Fisher’s exact test were used for comparisons. Results: 44 pts were randomized, 23 N, 21 NI: mean age 66, 64% males, 18% never smokers, 59% adenocarcinomas, stages: IA 8 (18%), IB 15 (34%), IIA 7 (16%) IIB 5 (11%); IIIA 9 (20%). Only 3 pts received &lt; 3 doses due to TRAEs (7%). 34 pts had surgery post ICIs (7 not resected [7/41], 17%, [2 N, 5 NI], 3 pending). There were 10 MPRs in 41 pts overall (24%, 4 N, 6 NI), of which 6 were path CRs (15%, 2 N [9%], 4 NI [21%]). Among 34 resected pts, MPR rate was 29% (N 20%, NI 43%). Median % of viable tumor was lower post NI vs N (20% vs 65%, p = .097). ORR (RECIST v1.1) was 22% (8 PRs [5 N, 3 NI], 1 CR [NI]); 15% of pts had PD (3 N, 3 NI). The proportion of CR+PR in MPR+ was higher than in MPR- (6 [60%] vs 2 [7%], p &lt; .001). Surgical complications included 2 bronchopleural fistulas (BPFs) in N &amp; 8 air leaks (5 N, 3 NI). G3-G5 TRAEs included a death due to BPF post steroid-treated pneumonitis (G5, N); G3 pneumonia, hypoxia, hypermagnesemia (1 each, all N), G3 diarrhea (1 NI). CD3 + &amp; CD103 + tissue resident memory CD8 + TILs were higher in NI- vs N-treated tumors (CD3 + 81.2% vs 54.4%, p = .028; CD8 + 56.2% vs 38.3%, p = .069). Median pre-treatment tumor PD-L1 was higher in responders (MPR+, CR+PR) vs non-responders (80% vs 1%, p = .024), and the % of viable tumor was lower in tumors with PD-L1 &gt; 1% vs PD-L1 ≤1% (median 20% vs 80%, p = .046). Conclusions: Overall a 24% MPR rate to neoadjuvant ICIs was observed. NI induced a higher % of non-viable tumor and of tissue resident memory TILs vs N. Antitumor activity was associated with higher pre-treatment PD-L1 levels. Clinical trial information: NCT03158129.