tbuckley/cabot-search huggingface dataset:
Safety data from an expanded access program (EAP) of nivolumab (NIVO) in combination with ipilimumab (IPI) in patients with advanced melanoma (MEL).
Authors: Paul B. Chapman, Mario Sznol, Christopher Lao, Rene Gonzalez, Gregory A. Daniels, John A. Thompson, Ragini Reiney Kudchadkar, William Howard Sharfman, Michael B. Atkins, Anna C. Pavlick, Jeffrey R. Infante, Kevin Kim, Jeffrey S. Weber, Sapna Pradyuman Patel, Suresh Nair, C. Lance Cowey, Evan J. Lipson, Sue Lee, Alexandre Avila, F. Stephen Hodi
Journal: Journal of Clinical Oncology (2016)

9525 Background: NIVO (anti-PD-1) and IPI (anti-CTLA-4), alone and in combination, are FDA-approved for the treatment of patients (pts) with MEL. Clinical trials have shown numerically longer progression-free survival with NIVO+IPI than with either agent alone. However, in the phase III study CheckMate 067, treatment-related grade 3/4 AEs were more common with NIVO+IPI (55%) than with NIVO (16%) or IPI (27%). Here, we report safety data from an EAP in the United States of NIVO+IPI in pts with MEL (CheckMate 218, NCT02186249). Methods: Pts received NIVO 1 mg/kg + IPI 3 mg/kg Q3W x 4, then NIVO 3 mg/kg Q2W until progression or a maximum of 48 weeks from the first monotherapy dose. Assessments included incidence of treatment-related AEs and select AEs (ie, those with a potential immunologic etiology). Data are from the first 6 months of treatment (database lock: November 2015). Results: Among 252 pts, median age was 59 years, 68% were male, 29% received ≥ 1 prior therapy, 98% had ECOG PS of 0 or 1, 77% had stage IV MEL, and 50% had M1c disease. The median number of NIVO doses received was between 3 and 4 (3.5, range: 1–22) and the median number of IPI doses received was 3 (range: 1–4). After treatment with NIVO+IPI, 99 pts (39%) continued to receive NIVO alone. 106/252 pts (42%) are still on treatment. Treatment-related AEs of any grade were reported in 233 pts (93%) and grade 3/4 in 130 pts (52%). The most common treatment-related grade 3/4 select AEs were gastrointestinal (GI) (18%) and hepatic (14%). Less common were skin (3%), renal (2%), and endocrine (2%) AEs; pancreatitis and pneumonitis occurred at < 1%. No treatment-related deaths were reported. Median time to onset for treatment-related grade 3/4 GI AEs (n = 46) was 6.6 weeks (range: 0.4–16.1) and for hepatic AEs (n = 36) was 8.6 weeks (range: 1.0–17.0). Treatment-related grade 3/4 AEs leading to discontinuation were reported in 58 pts (23%). Conclusions: Pt demographics in this EAP were similar to those reported in the phase III study CheckMate 067, except that there were pts on the EAP who received prior systemic therapies for MEL. The overall safety profile in this EAP was consistent with prior clinical trial experience. Clinical trial information: NCT02186249.
Impact of TNM staging, treatment, primary site on survival rates of hypopharyngeal squamous cell carcinoma: A population-based analysis.
Authors: Gehad Mohamed Tawfik, Muhammad Salman Faisal, Nguyen Lam Vuong, Muhammed Khaled Elfaituri, Amr Ebied, Thuan Minh Tieu, To Kim Sang, Amr G. Shafik, Nguyen Tien Huy
Journal: Journal of Clinical Oncology (2018)

e18028 Background: Our aim to analyze associations between (TNM staging, treatment modalities, primary site) and hypopharyngeal cancer survival in US between 2004 and 2013. Methods: A retrospective cohort study of 3,433 hypopharyngeal cancer patients with SCC, identified in SEER database. They were evaluated for survival rates with prediction of cause-specific survival and overall survival by using Kaplan-Meier analysis and univariate and multivariate Cox regression. Results: Compared to 2004, there were significant decreases in all-cause mortality in 2006 and 2007, HR [95%CI] were 0.825 [0.695-0.978] and 0.836 [0.704-0.991], respectively. Posterior pharyngeal wall showed worse survival compared to pyriform sinus (1.192 [1.001-1.420]). Regarding treatment modality, radiation combined with surgery have better survival rate compared to radiation only (1.345 [1.179-1.533]) and surgery only (1.539 [1.197-1.978]). Regarding TNM staging, in AJCC stage 3, T3N0M0 and T3N1M0 had significantly worse survival than T1N1M0 (1.750 [1.170-2.618] and 1.703 [1.122-2.584], respectively). In AJCC stage 4A, T2N2M0, T3N2M0, T4aN0M0, T4aN1M0 and T4aN2M0 had significantly worse survival than T1N2M0 (1.452 [1.083-1.947], 1.622 [1.192-2.208], 1.963 [1.429-2.696], 2.278 [1.655-3.135] and 2.194 [1.641-2.933], respectively). In stage 4B, T4bN1M0 and T4bN3M0 had significantly worse survival than T1N3M0 (2.328 [1.035-5.236] and 3.717 [1.578-8.754], respectively). Multivariate analysis revealed that older age, race (Black compared to White), marital status (single, divorced or widowed compared to married), primary site (Posterior wall of hypopharynx compared to pyriform sinus) and treatment (surgery combined with radiation compared with surgery or radiation only) were all significantly associated with worse survival. Conclusions: Primary site in posterior wall of hypopharynx has worse survival compared to pyriform sinus. In each of stage 3, 4A and 4B, increase T-stage is associated with worse survival. Radiation combined with surgery is associated with improved survival compared with radiation/surgery only.
The impact of clinical stage at primary melanoma diagnosis on post-recurrence survival.
Authors: Kierstin Utter, Brooke E Rosenbaum, Sung Won Han, Judy Zhong, Una Moran, Eleazar Vega-Saenz de Miera, Farbod Darvishian, David Polsky, Russell S. Berman, Richard L. Shapiro, Iman Osman, Anna C. Pavlick, Melissa Wilson
Journal: Journal of Clinical Oncology (2016)

9550 Background: Time to metastatic recurrence from primary melanoma diagnosis is known to vary based on original stage at diagnosis. However, little is known on whether recurrent melanoma originating from distinct primary stages will converge to similar clinical behavior once they are metastatic. We investigated the association between initial clinical stage at original diagnosis (ICS) and overall survival following diagnosis of stage IV disease (OS). Methods: Stage IV melanoma patients prospectively accrued in the NYU melanoma database from 2002-15 were identified. Patients were categorized into groups based on ICS as defined by AJCC criteria. Kaplan-Meier (KM) was used to evaluate OS based on ICS and treatment type. Univariate and multivariate Cox regression analyses were used to test association between ICS and OS. Results: Of 388 stage IV patients studied, 97 (26%) presented at ICS-I, 101 (27%) at ICS-II, 114 (31%) at ICS-III, and 61 (16%) at ICS-IV. KM analysis showed that patients initially diagnosed at ICS-I had longer OS than those diagnosed at ICS-II, III, or IV (mOS 1.4y, 1.1y, 1.1y, 0.9y, respectively; p = 0.03). Patients who received prior adjuvant therapy had better OS than those who did not (mOS 2.0y vs 1.1y; p < 0.01), as did patients who received immunotherapy at the time of metastatic disease compared to those who did not, regardless of ICS (mOS 1.4y vs 0.8y; p < 0.01). No difference in OS was observed with targeted therapy or chemotherapy. On univariate analysis, patients who presented at ICS-II, III, or IV had increased risk of death compared to those who presented at ICS-I (HR 1.41 p = 0.05, HR 1.44 p = 0.03, HR 1.59 p = 0.02, respectively). In multivariate analysis controlling for clinicopathologic characteristics, patients who presented at ICS-II, III, or IV did not have a significantly increased risk of death compared to those who were diagnosed at ICS-I (HR 1.21 p = 0.79, HR 1.09 p = 0.91, respectively). Conclusions: Our data suggest a possible difference in tumor progression among stage IV melanoma patients based on ICS, despite their convergence to metastatic disease. Our findings warrant further evaluation of the potential implications of initial clinical stage and adjuvant therapy on outcomes in stage IV melanoma patients.
Abstract 18972: Iron Quantification in Carotid Artery Atherosclerosis Predicts Downstream Injury by Magnetic Resonance Imaging
Authors: Travis P Sharkey-Toppen, Tam Tran, Suzanne Smart, Beth McCarthy, Xuan Nguyen, Subha V Raman
Journal: Circulation (2014)

Introduction: Luminal stenosis is the primary imaging parameter used to guide management of patients with carotid artery atherosclerosis (CAA). However, neuroimaging identifies subclinical events in patients with CAA not meeting anatomic guidelines for intervention. Strategies to characterize atherosclerotic plaque beyond %stenosis may help reduce the downstream ischemic burden of atherosclerotic disease. Hypothesis: Using noncontrast MRI T2* tissue mapping that we have previously validated for plaque iron characterization, we tested the hypothesis that carotid plaque T2* better predicts ischemic injury by brain MRI than symptom history. Methods: We enrolled 26 individuals with carotid artery stenosis ≥50%. Each subject underwent MRI that included carotid plaque T2* mapping (TR=75ms, 5 TEs, 20° flip angle, 0.44x0.44x2mm resolution), brain diffusion weighted imaging (TR=4436ms, TE=93ms, 0.9x0.9x3mm resolution) and brain fluid attenuated inverse recovery imaging (TR=13970ms, TE=2500ms, 150° flip angle, and 0.9x0.9x3mm resolution). Plaque T2* quantification and brain MRI were independently assessed by experienced observers blinded to patient history and other results. Brain MRIs with Wahlund score ≥2 were classified as positive for ischemic damage. Results: Patients with brain imaging positive for ischemic damage had shorter intraplaque T2* compared to patients with negative brain MRI (17.2±2.9 vs. 20.3±3.2ms, p=.012, Figure). Conversely, presence/absence of brain injury did not correlate with symptoms (p=.352). Conclusions: Noncontrast atherosclerosis imaging using an MRI biomarker of intraplaque iron in patients with carotid artery disease can discriminate between patients with vs. those without ischemic brain injury. Prospective studies that couple plaque characterization with anatomic and clinical factors may better identify at-risk patients with carotid artery disease before significant ischemic brain injury has accrued.
Outcomes by number of induction cycles with CPX-351 vs 7+3 chemotherapy in older adults with newly diagnosed, high-risk/secondary acute myeloid leukemia (sAML).
Authors: Tara L. Lin, Bruno C. Medeiros, Geoffrey L. Uy, Laura Fugal Newell, Ellen K. Ritchie, Robert K. Stuart, Stephen Anthony Strickland, Donna Hogge, Scott R. Solomon, Richard M. Stone, Dale L. Bixby, Jonathan E. Kolitz, Gary J. Schiller, Matthew Joseph Wieduwilt, Daniel H. Ryan, Robert J Ryan, Michael Chiarella, Arthur Chin Louie, Jeffrey E. Lancet, Jorge E. Cortes
Journal: Journal of Clinical Oncology (2018)

7040 Background: CPX-351, a liposomal encapsulation of cytarabine (C) and daunorubicin (D) at a synergistic ratio, is approved in the US for treatment of adults with newly diagnosed therapy-related AML or AML with myelodysplasia-related changes. In a phase 3 study, CPX-351 improved survival and remission rates vs 7+3 in patients (pts) aged 60-75 y with newly diagnosed high-risk/sAML. This exploratory analysis compared outcomes in 1 vs 2 induction phases. Methods: Pts were randomized 1:1 to receive 1-2 inductions of CPX-351 (100 units/m2 [C 100 mg/m2 + D 44 mg/m2] on Days 1, 3, 5 [2nd induction: Days 1, 3]) or 7+3 (C 100 mg/m2/d continuously for 7 d [2nd induction: 5 d] + D 60 mg/m2 on Days 1-3 [2nd induction: Days 1-2]). Pts achieving complete remission (CR) or CR with incomplete platelet or neutrophil recovery (CRi) could receive up to 2 consolidations. Results: 304 pts were treated with CPX-351 (n = 153) or 7+3 (n = 151). A greater proportion of pts treated with CPX-351 achieved remission after 1 induction vs 7+3 (CR: 45% vs 28%; CR+CRi: 55% vs 34%; Table). Remission rates after 2 inductions were comparable between arms (CR: 21% vs 24%; CR+CRi: 31% vs 35%; Table). The frequency of grade 3-5 treatment-emergent adverse events (TEAEs) in pts with 1 induction was similar for CPX-351 (75/105 [71%]) vs 7+3 (74/100 [74%]). In pts with 2 inductions, fewer pts had grade 3-5 TEAEs with CPX-351 (38/48 [79%]) vs 7+3 (48/51 [94%]). Febrile neutropenia was the most common grade 3-5 TEAE with both CPX-351 and 7+3 (1 induction: 58% vs 57%; 2 inductions: 60% vs 80%). Serious TEAEs were similar with CPX-351 and 7+3 (1 induction: 33% vs 33%; 2 inductions: 29% vs 26%). Conclusions: Pts treated with CPX-351 were more likely to achieve remission after 1 induction vs 7+3; remission rates were similar after 2 inductions. Pts who received CPX-351 had a similar frequency of grade 3-5 TEAEs after 1 induction and fewer grade 3-5 TEAEs after 2 inductions vs 7+3 pts. Clinical trial information: NCT01696084. 1 induction 2 inductions CPX-351 7+3 Odds ratio CPX-351 7+3 Odds ratio (n = 105) (n = 100) (95% CI) (n = 48) (n = 51) (95% CI) CR, n (%) 47 (45) 28 (28) 2.08 (1.17, 3.73) 10 (21) 12 (24) 0.86 (0.33, 2.21) CR+CRi, n (%) 58 (55) 34 (34) 2.40 (1.36, 4.21) 15 (31) 18 (35) 0.83 (0.36, 1.93)
Phase II trial of nintedanib in patients with recurrent or metastatic salivary gland cancer: A multicenter phase II study.
Authors: Youjin Kim, Su Jin Lee, Keunchil Park, Se-hoon Lee, Jong Mu Sun, Bhumsuk Keam, Ho Jung An, Jae Yong Cho, Jin-Soo Kim, Ha-young Lee, HyeRyun Kim, Kyoung Eun Lee, Moon Young Choi, Ki Hyeong Lee, Myung-Ju Ahn
Journal: Journal of Clinical Oncology (2016)

6090 Background: Salivary gland cancers (SGC) are histologically uncommon but heterogeneous, accounting for less than 5% of all head and neck cancers. No specific therapy including targeted agents has been associated with improved clinical outcome in recurrent/metastatic SGC. Recent studies suggest VEGF and PDGFR might play an important role in SGC. Nintedanib is a potent small molecule triple receptor tyrosine kinase inhibitor (VEGFR1-3, FGFR 1-2, and PDGFR α/ß). We sought to determine nintedanib’s antitumor activity in patients with recurrent or metastatic SGC. Methods: This open-label, multicenter, phase II, single-arm study was conducted at 11 hospitals in Korea. Patients with pathologically confirmed recurrent and/or metastatic SGC who had undergone cytotoxic chemotherapy were enrolled. Nintedanib was given orally at 200mg twice daily until disease progression or unacceptable toxicity. The primary endpoint was response rate. Secondary endpoints were progression-free survival, overall survival, toxicity, and disease control rates. Simon two-stage optimal design was used. Results: Median age was 54 years, 62% of patients were female, and 95% had an ECOG performance status of 0 or 1. The majority of patients had adenoid cystic carcinoma (65%), and 40% of all of patients had received at least two prior chemotherapies. After 20 patients were enrolled, the study was stopped because no responder was observed at Stage I. There was no partial response, but the disease control rate was 75% (15/20). The median duration of stable disease was 8.3 months (range 3.5-12.4). At the time of data cutoff with median follow-up of 9.5 months, median overall survival had not been reached, and the progression-free survival rate at 6 months was 60% (CI.0.34-0.79). Grade 3 adverse events included liver enzyme elevation (25%) and nausea/vomiting (5%). Five patients required dose reduction. Conclusions: Single agent nintedanib did not show partial response, but did achieve a 75% control rate with long stabilization in these SGC patients. Nintedanib was tolerable and toxicities were manageable. Given the high rate and long duration of disease control, further investigation is needed. Clinical trial information: NCT02558387.
BPI-9016M, a novel c-Met inhibitor, in pretreated advanced solid tumor: Results from a first-in-human, phase I, dose-escalation study.
Authors: Xingsheng Hu, Xin Zheng, Hongnan Mo, Xinge Cui, Lieming Ding, Fenlai Tan, Pei Hu, Yuankai Shi
Journal: Journal of Clinical Oncology (2018)

e21108 Background: BPI-9016M (Betta Pharmaceuticals Co, Ltd, Hangzhou, China) is a potent targeted therapy that inhibits MET and Axl. This first-in-human study is to assess the safety, tolerability, and PK of BPI-9016M in patients with advanced solid tumor malignancy, and to determine the MTD and RP2D for the phase Ib/II study. Methods: Eligible patients were enrolled into sequential dose-escalating cohorts from 100 mg to 1000 mg given orally once per day continually following the conventional 3+3 design. The primary endpoint was safety and tolerability. MTD was defined as the highest dose level resulting in < 1 of 3 DLTs. Blood levels of BPI-9016M were evaluated after single and multiple administration. This study was registered on ClinicalTrials.gov as NCT02478866. Results: Twenty patients were enrolled and treated in 6 of 7 predefined dose cohorts (100 mg n = 4, 200 mg n = 3, 300 mg n = 3, 450 mg n = 4, 600 mg n = 3, 800 mg n = 3), all had stage IV non-small cell lung cancer (NSCLC) progressed on previous systemic therapy (including previous EGFR TKI in 16 patients). BPI-9016M was well-tolerated in all dose cohorts without DLT. The incidence of overall and grade 3/4 TRAEs was 85% and 45%, respectively. Common TRAEs included elevated ALT (45%), constipation (30%), elevated bilirubin (25%), and oral paresthesia (25%). Tumor response was seen in 1 patients in the 800 mg dose cohort. Systemic exposure to BPI-9016M (maximum plasma concentration and AUC) increased with increasing dose. Mean time to maximum plasma concentration and half-life were 10.07 to 22.19 hours and 2 to 5.33 hours, respectively. Two metabolites (M1, M2-2) were detected. Conclusions: BPI-9016M was well tolerated in patients with advanced solid tumor. A phase Ib study is ongoing to investigate the safety and activity of BPI-9016M in patients with c-Met-dysregulated advanced NSCLC (NCT02929290). Clinical trial information: NCT02478866.
Using the GeneReader NGS system and QIAact lung all-in-one assay to detect complex mutations and fusions.
Authors: Simon Hughes, Paola Arzuffi, John Blood, Alexander Burton, Vikas Gupta, Dietrich Lueerssen, Leif Schauser, Juergen Lauber
Journal: Journal of Clinical Oncology (2018)

e21193 Background: Lung cancer is the cause of 1 in 5 cancer deaths worldwide and is frequently driven by somatic mutations acquired in key genes. Targeted Next-Generation Sequencing (NGS) is a valuable tool for identifying mutations in these genes and has improved our understanding of disease progression. However, these mutations are not limited to just single nucleotide variants (SNV) or Insertion/Deletions (InDel) but also include complex chromosomal changes such as copy number variants (CNV) and fusions. Methods: The GeneRead QIAact Lung All-in-One Assay has been designed to include 549 DNA variants and 5 CNVs, plus 79 RNA fusions (including MET exon 14 skipping) known to be important in lung cancer. Samples used in this study were formalin-fixed paraffin embedded (FFPE) reference standards, CNV positive cell lines, and FFPE lung cancer samples. Following target enrichment of DNA and RNA using the GeneRead QIAact Lung All-in-One Assay the libraries were sequenced on the GeneReader™ and mutations assessed using QIAGEN Clinical Insight (QCI™) Analyze. Results: To confirm both DNA and RNA mutation detection, Horizon® Discovery Reference Standards containing DNA (SNVs and InDels) and RNA (fusions) mutations, typical of FFPE samples (Quantitative Multiplex and ALK-RET-ROS1 Fusion RNA Reference Standard), and well-characterized cell lines were used. All expected DNA (5% allele frequency threshold appropriate for FFPE DNA) and RNA mutations were repeatedly identified both within and between runs. Testing of clinical samples consistently detected the expected RNA fusions (EML4-ALK) and DNA mutations (EGFR and KRAS mutations) previously identified by FISH or quantitative PCR (QIAGEN therascreen®), respectively. Conclusions: These data showcase the performance reliability of the QIAact All-in-One Assay on the GeneReader NGS System. This is the first study of its kind to systematically demonstrate the ability of a single assay to test for a wide range of mutations including complex chromosomal rearrangements. This allows a laboratory to accurately detect actionable lung cancer mutations with a single NGS assay in one seamless workflow, greatly improving efficiency and effectiveness.
Evaluation of capecitabine in patients with platinum-pretreated advanced or recurrent cervical carcinoma: A retrospective study of the IRCCS National Cancer Institute of Milan.
Authors: Domenica Lorusso, Stefano Lepori, Ilaria Sabatucci, Elisa Tripodi, Giuseppa Maltese, Giorgio Bogani, Umberto Leone Roberti Maggiore, Antonino Ditto, Fabio Martinelli, Diego Rossetti, Francesco Raspagliesi
Journal: Journal of Clinical Oncology (2018)

5535 Background: Cervical cancer is underrepresented in the gynecological clinical research. The objective of this retrospective study was to evaluate the activity and the safety of capecitabine in patients with platinum-pretreated recurrent cervical carcinoma. Methods: We performed a retrospective review of medical records from patients with advanced or recurrent cervical carcinoma pretreated with platinum-based therapy who received oral capecitabine at the Gynecological Units of the IRCCS National Cancer Institute of Milan (Italy). We used Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 to evaluate response to therapy and Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 to evaluate adverse events. Results: From October 2013 to August 2017, we treated with oral capecitabine dose 29 patients with advanced or recurrence cervical carcinoma, already exposed to platinum. All patients receive a combination of carboplatin plus paclitaxel as first-line therapy for advanced/recurrent disease. At first capecitabine administration the median of previous treatments was 2 (range from 1 to 5). After three cycles of oral capecitabine the clinical benefit rate (CBR) was 62% with 41.3% of PR and 20.7% of SD. Grade 3 reported toxicity were 10% neutropenia and 3% hypertransaminasemia. CBR was 83.3% in adenocarcinomas versus 47% in squamous cell carcinomas. The most frequent grade 1 or 2 adverse events were fatigue (55%), hand-foot syndrome (38%) and diarrhea (24%). Conclusions: Our study suggests that oral capecitabine should be considered an active and safe treatment in patients with platinum-pretreated advanced or recurrent cervical carcinoma.