tbuckley/cabot-search huggingface dataset:
Dovitinib as second-line therapy in patients with fibroblast growth factor receptor 2 (FGFR2)-mutated or non-mutated advanced and/or metastatic endometrial cancer (EC): A single-arm, multicenter, phase II study.
Authors: Gottfried E. Konecny, Neil Finkler, Agustin Garcia, Francesco Raspagliesi, Carolina Muriel Lopez, Michael McCollum, M Jesus Rubio, Matthew Squires, Nicoletta Pirotta, Allison Upalawanna, Alejandro Javier Yovine, Rodney Paul Rocconi
Journal: Journal of Clinical Oncology (2013)

TPS5616 Background: Despite the use of combination chemotherapy and introduction of novel targeted agents, the prognosis for advanced and/or metastatic EC is challenging. The occurrence of somatic activating FGFR2 mutations in EC suggests an opportunity for testing FGFR inhibitors. Dovitnib (DOV) is a potent receptor tyrosine kinase inhibitor of vascular endothelial growth factor receptor, platelet-derived growth factor receptor and FGFR. The objective of the study is to investigate the efficacy and safety of DOV as second-line therapy in patients (pts) with advanced and/or metastatic EC. Methods: This multicenter, non-randomized, open label, single-arm, phase II study (NCT01379534) will enroll adult female pts (N~80) with either FGFR2 mutated (group 1) or non-mutated (group 2) histologically confirmed advanced and/or metastatic EC, who have documented radiological evidence of progressive disease (RECISTv1.1) after 1 prior line of chemotherapy, excluding adjuvant therapy. Eligible pts also need to have ≥1 measurable lesion (RECISTv1.1) and ECOG performance status ≤ 2. Pts will receive oral DOV of 500 mg/day, on a 5-days-on / 2-days-off dosing schedule until disease progression, unacceptable toxicity, death, or discontinuation due to any other reason. Primary endpoint is 18-week progression-free survival (PFS) rate (local review; RECIST v1.1) and secondary endpoints include overall response rate, disease control rate, duration of response, PFS, overall survival, safety, tolerability, pharmacokinetics, and pharmacodynamic effect of DOV on soluble plasma biomarker expression level. A 2-stage design with Bayesian interim monitoring (interim for futility analyses) will be used in each group. For stage 1, 20 pts will be enrolled into each group. If ≥ 8 of the first 20 pts with measurable disease at baseline in either group are progression-free after 18 weeks of treatment, 20 additional pts will be enrolled into that group in stage 2. Preliminary results for each group will be evaluated in the interim analysis. As of 20 January 2013, 43 pts have been enrolled (12 with and 31 without FGFR2 mutations). Clinical trial information: NCT01379534.
Array CGH and DNA sequencing to personalize targeted treatment of metastatic breast cancer (MBC) patients (pts): A prospective multicentric trial (SAFIR01).
Authors: Fabrice Andre, Thomas Denis Bachelot, Mario Campone, Monica Arnedos, Veronique Dieras, Magali Lacroix-Triki, Vladimir Lazar, David Gentien, Pascale Cohen, Anthony Goncalves, Ludovic Lacroix, Max Chaffanet, Florence Dalenc, Marie-Christine Mathieu, Ivan Bieche, Sylviane Olschwang, Qing Wang, Frederic Commo, Marta Jimenez, Herve R. Bonnefoi
Journal: Journal of Clinical Oncology (2013)

511 Background: The aim of the present study was to profile the metastatic lesion of pts using high throughput technologies, and to treat them accordingly. Methods: SAFIR01 trial aimed to include 400 pts with MBC, selected for not presenting a progressive disease at the time of biopsy. A biopsy was done in a metastatic site. DNA was extracted if the tumor contained &gt;50% cancer cells, and sent to one of the 5 genomic centers who performed array CGH (copy number changes) and sanger sequencing on PIK3CA (exon 10/21) and AKT1 (exon 3). A targeted therapy matched to the genomic alteration was expected to be proposed at the time of progressive disease. The primary endpoint was the % of pts who received a targeted therapy according to the genomic alteration. Results: A biopsy of metastatic site was done successfully in 408 out of the 423 included pts. Biopsy was complicated by a serious adverse event in 9 pts. A discrepancy between primary and metastatic lesion was observed in 8% and 19% of pts for Her2 and HR. Array CGH and sequencing were successfully obtained in 277 (68%) and 295 (72%) pts. The main reason for failure of genomic test was the low cellularity (n=93). A targetable genomic alteration was identified in 204 pts. The most frequent genomic alterations were PIK3CA mutations, CCND1, FGF4 and FGFR1 amplifications. 76 pts presented a rare targetable genomic alteration (&lt;5%), including AKT1 mutations, EGFR, FGFR2, PIK3CA, MDM2 amplifications. Early Feb 2013, 4 6 out of 277 pts with genomic analyses (17%) had received a targeted therapy matched to the genomic alteration, covering twelve different targets. Updated results on number of pts treated, together with efficacy data will be presented. Next generation sequencing on metastatic lesions is ongoing and results will be presented. Conclusions: This trial evaluated the concept of personalized medicine for MBC and provided a large scale genomic analysis of metastatic tissue. This study suggests that assessing the biology of metastatic tissue could allow driving pts to targeted therapy. A randomized trial (SAFIR02) testing this approach is expected to start during summer 2013. Clinical trial information: NCT01414933.
Prevalence of prescribing errors resulting in administration of incorrect dosages of antineoplastic treatment.
Authors: Thea Otto Mattsson, Bente Holm, Hanne Marie Michelsen, Janne Lehmann Knudsen, Kim Brixen, Jorn Herrstedt
Journal: Journal of Clinical Oncology (2014)

6614 Background: The prevalence of non-intercepted prescribing errors and the impact of computerized order entry systems (CPOE) in preventing such errors are not known. Our objective was to evaluate both prevalence and severity of non-intercepted prescription dose errors as well as the impact of a CPOE system on these in a setting of adult cancer patients. Methods: A prospective observational case control study in two clinical oncology units. One institution used a parallel CPOE system with no connection to the electronic patient chart data, while the other used paper based prescription forms. All standard prescriptions from both institutions were included and reviewed. Doses were recalculated according to the guidelines of each of the institutions using the patient data as documented in the chart, on the paper based form or in the CPOE system at the time of prescription. A non-intercepted prescription dose error was defined as ≥ 10% difference between the administered and the recalculated dose. Main outcome measures were prevalence and severity of prescription errors using validated harm categories. Results: Data were collected from November 1, 2012 til January 31, 2013. A total of 5,767 physician prescriptions were evaluated. 2,677 from the institution using CPOE and 3090 from the institution with paper based prescription forms. Crude analysis showed an overall risk of a prescription dose error of 1.73 per 100 prescriptions. CPOE resulted in 1.60 and paper based prescription forms in 1.84 errors per 100 prescriptions. OR = 0.87 (95%CI 0.59-1.29, P=0.49). Furthermore, no significant difference between institutions in severity of errors was observed. Conclusions: Non-intercepted prescribing dose errors are relatively common in clinical oncology units. Non integrated CPOE systems without decision support do not seem to significantly reduce the risk of prescription errors or affect severity of errors. Based on the results of this study strategies to prevent future prescription errors are highly warranted.
Pressure pain sensitivity: a new method of stress 2 measurement in patients with ischemic heart disease
Authors: N. Bergmann, S. Ballegaard, P. Holmager, J. Kristiansen, F. Gyntelberg, L. J. Andersen, A. Hjalmarson, P Bech, Lars Arendt-Nielsen, Jens Faber
Journal: Psychotherapy and Psychosomatics (2013)
The predictive value of protein, glucose, and lactate for a diagnosis of neoplastic meningitis.
Authors: Jonathan McClain, Michael J. Glantz
Journal: Journal of Clinical Oncology (2012)

e12005 Background: Neoplastic Meningitis (NM) is a complication of many common cancers that occurs with an incidence as high as 15% in some cancer types. Diagnosis remains elusive with poor screening tools and insensitive diagnostic options. Methods: A retrospective analysis of 341 consecutive patients with suspected NM was undertaken. Clinical presentation, demographic, cytologic and MRI data were recorded. Using cytology as the diagnostic gold standard, sensitivity, specificity, ROC curves and likelihood ratios were calculated. Results: 210 patients met inclusion criteria, 87 with primary brain tumors (PBT), 72 with non-CNS solid tumors, and 44 with lymphomas. 111 patients were male; 123 (58.6%) ultimately had a positive cytology. Only 59% of patients with positive cytology presented with symptoms concerning for NM. 32.9% of patients with PBTs and positive CSF cytology exhibited neurologic symptoms suggestive of NM. Patients with non-CNS solid tumors and positive CSF cytology presented with symptoms concerning for NM 80% of the time. Patients with cytology-positive, MRI-positive and symptom-positive NM had very different survivals. Potentially informative CSF values are in table below. Conclusions: A definitive diagnosis for patients with suspected NM remains elusive without a positive cytology, but some clinical, radiographic, and CSF findings are useful for raising diagnostic concern, and for screening in at-risk populations. Symptom-positive or MRI-positive NM may represent different diseases than cytology-positive NM. [Table: see text]
Development and validation of the functional assessment of cancer therapy: Antiangiogenesis (FACT-AntiA).
Authors: Susan Yount, Karen Kaiser, Jennifer L Beaumont, Kimberly Webster, Lynne I. Wagner, Tom L. Schenk, Timothy Kuzel, David Cella
Journal: Journal of Clinical Oncology (2013)

e20527 Background: Anti-angiogenesis therapies represent a significant and promising advancement in cancer treatment. Side effects from angiogenesis inhibitors, although generally milder than chemotherapy side effects, have the potential to impact Health-related Quality of Life (HRQOL) and may lead to dose reduction or discontinuation. Currently, there are no patient-reported outcomes (PRO) measures that specifically assess HRQOL related to anti-angiogenesis therapy. This study describes the development and validation of a PRO questionnaire for anti-angiogenesis therapy, the FACT-AntiA. Methods: Scale development included identification of 59 anti-angiogenesis side effects from the literature and clinician and patient input. Patient and clinician ratings of the importance of these side effects led to the development of a 24-item scale. Cognitive interviews with 10 patients confirmed item wording and meaning. To assess psychometric properties of the scale, 132 kidney cancer patients completed the FACT-AntiA and other PRO measures including the Functional Assessment of Cancer Therapy-General (FACT-G), the FACT-Kidney Cancer Symptom Index-19 (FKSI-19), and PROMIS Global Health at 3 time points. Patient responses to the FACT-AntiA were analyzed for internal consistency, test-retest reliability, convergent and discriminant validity, and responsiveness to change in clinical status. Results: FACT-AntiA side-effect subscales scores and total score were found to have good internal consistency reliability (most Cronbach’s alpha &gt; 0.70). Test-retest reliability was greater than 0.70 for most subscales and individual items. All single items (except nosebleeds), subscales, and the total score significantly differentiated between groups defined by level of side effect bother. Conclusions: The number of patients who reported a change in their side effect bother was small so evaluation of FACT-AntiA responsiveness to change requires further study. The FACT-AntiA was developed and validated as a tool to enhance treatment decision-making and side effect management for patients receiving anti-angiogenesis therapies and is a reliable and valid index for evaluation of therapy side effects.
Updated results of a phase 1 study combining the matrix metalloproteinase 9 inhibitor GS-5745 and mFOLFOX6 in patients with advanced gastric/gastroesophageal junction cancer.
Authors: Manish A. Shah, Alexander Starodub, Jordan Berlin, Carrie Baker Brachmann, Xi Huang, Victoria Smith, Julia D. Maltzman, Zev A. Wainberg, Johanna C. Bendell
Journal: Journal of Clinical Oncology (2017)

108 Background: GS-5745 is a monoclonal antibody inhibitor of matrix metalloproteinase 9 (MMP9), an extracellular enzyme involved in matrix remodeling, tumor growth, and metastasis. We present updated data from a phase I study of patients (pts) with advanced gastric/gastroesophageal adenocarcinoma (GC) treated with GS-5745 and mFOLFOX6 (NCT01803282). Methods: Following a monotherapy dose finding stage, pts with Human Epidermal Growth Factor Receptor 2 (HER2)-negative advanced or metastatic GC received mFOLFOX6 and GS-5745 (800 mg IV) every 2 weeks. Treatment continued until disease progression, unacceptable toxicity or withdrawal of consent. Response was assessed every 8 weeks per RECIST version 1.1 criteria. Results: As of April 2016, 40 pts were enrolled in the expanded cohort (12 continue to receive GS-5745). The most frequently observed adverse events (AEs) of any grade include nausea (62.5%), fatigue (60%), diarrhea (45%), peripheral neuropathy (45%) and neutropenia (37.5%). Grade ≥ 3 AEs observed in ≥ 10% of pts include neutropenia (20%) and nausea and neutrophil count decreased (10% each). Among 29 treatment naïve pts, median progression free survival (PFS) is 12 (90% confidence interval (CI) 5.5-18) months (mos), median duration of response (DOR) 10.6 mos and objective response rate (ORR) of 55.2%. For all pts (n=40), PFS is 7.8 (90% CI 5-13.9) mos, median DOR 10.1 mos and ORR of 50%. Median baseline circulating MMP9 was 44.7 (range 16.8-1395.3) ng/mL and all 34 patients with post-baseline samples had undetectable MMP9 levels within 8 weeks. Conclusions: The combination of GS-5745 with mFOLFOX6 is well tolerated and demonstrates activity, particularly in treatment naïve pts. Reduction in circulating MMP9 level after treatment with GS-5745 suggests specific target engagement. A phase III registration study of mFOLFOX6 +/- GS-5745 in treatment naïve metastatic GC pts is underway. Clinical trial information: NCT01803282.
Outcome and prognostic factors in BRAF mutation positive metastatic melanoma treated with a BRAF inhibitor: A population-based study in British Columbia.
Authors: Joanna Vergidis, Richard John Klasa, Youwen Zhou, Elena Moon, Debbie Jepson, Kerry J. Savage
Journal: Journal of Clinical Oncology (2013)

e20045 Background: BRAF mutations are present in approximately 40-60% of cutaneous melanomas. The BRAF inhibitor vemurafenib has demonstrated dramatic anti-tumour activity in phase III trials in BRAF mutation positive (BRAFm) metastatic/unresectable melanoma; however, there is limited data outside of clinical trials. Methods: All patients &gt; 18 years of age, PS 0-2, with metastatic/unresectable melanoma considered for treatment with vemurafenib in British Columbia between March 2011 to December 2012 were identified. CNS disease, if present, had to be radiographically stable/asymptomatic and treated with radiation and/or surgery. The BRAF V600E mutation status was evaluated centrally on primary or metastatic biopsies using a real-time PCR assay (Cobas 4800 BRAF Mutation Test, Roche Molecular Systems). Vemurafenib was initially provided through an Expanded Access Program/Roche patient assistance program and subsequently through provincial funding. Results: In total, 84 patients were identified that had undergone BRAF mutation screening, 49(58%) were BRAFm, 35(42%) were BRAFwt. For the BRAFm patients 33 have received 1 cycle of vemurafenib and are included in the present analysis (n=21 (64%) 1st line therapy; 12(36%) &gt; 1st line therapy). BRAFm patients: median age 53 y; 64% male; PS 0/1 76%; LDH elevated 51.5%; M1c 91%; 27% history CNS metastases. With a median follow-up of 4.9 m the median PFS, measured from the 1st dose of vemurafenib, was 9 m and the median OS was 12.4 m. The 1 year PFS and OS were 47% and 50%, respectively. The median OS of patients who progressed following vemurafenib was only 2 months. There was an inferior PFS in patients with an elevated LDH (median PFS 5 m vs not reached, p=0.024) prior to receiving vemurafenib. Conclusions: The efficacy of vemurafenibin BRAF + melanoma in this population-based analysis compares favorably to estimates in the clinical trial setting. The survival of patients who progress on vemurafenib is short, highlighting the need to explore combination therapies. An updated analysis will be presented.
Validation of the total illness burden index for prostate cancer (TIBI-CaP) in men with castration-resistant prostate cancer (CRPC): Data from TRUMPET.
Authors: Scott Flanders, Samuel D. Wilson, Janet Kim, Sheldon Greenfield, Sherrie H. Kaplan, John Billimek, Arie Barlev, Elaine Wong, Daniel W. Lin, Lawrence Ivan Karsh, David I. Quinn, Daniel H. Shevrin, Neal D. Shore, James Thomas Symanowski, David F. Penson
Journal: Journal of Clinical Oncology (2017)

256 Background: The TRUMPET registry is a prospective, observational cohort study of patients (pts) with CRPC designed to evaluate treatment patterns and health-related quality of life (HRQoL) outcomes associated with CRPC and its management in a real-world setting. Comorbidities may influence how physicians approach CRPC treatment; therefore, evaluation of comorbidity presence and severity is important. The TIBI-CaP questionnaire measures comorbidity, with the aim of this analysis to validate TIBI-CaP in CRPC. Methods: Data were collected from 302 enrolled CRPC pts treated in academic and community-based sites under routine care. Baseline data collected included clinical history and self-reported demographics, comorbidities, and HRQoL. TIBI-CaP scores were analyzed based on correlation analysis and analysis of variance (ANOVA). Estimated correlations were used to verify the association of TIBI-CaP scores to scores on the SF-12v2 and FACT-P questionnaires. ANOVA models were run with SF-12v2 and FACT-P as response and quartile ranges for TIBI-CaP scores as predictor. Results: Mean age was 73.7 years. 84.7% were white; 13.9% were black. 87.8% had M1 CRPC at study entry. Mean (SD) TIBI-CaP score was 5.3 (2.72) [range 0-13], with 42.4% of CRPC pts presenting with moderate/severe comorbidity burden (higher scores). TIBI-CaP scores had statistically significant (p value &lt; 0.0002) negative correlations with all SF-12v2 composite and domain scores. Correlation estimates for physical condition and mental condition scores were -0.46 and -0.23, respectively. TIBI-CaP scores also had statistically significant (p value &lt; 0.02) negative correlations with FACT-P total scores and all subscales. FACT-P total scores had a -0.44 correlation estimate. F-tests showed significant differences across the four quartiles of TIBI-CaP scores and SF-12v2 and FACT-P (all p values &lt; 0.05). Conclusions: At baseline, TIBI-CaP scores were negatively correlated with CRPC pts baseline functional status as measured by the SF-12v2 and FACT-P questionnaires. TIBI-CaP was strongly associated with HRQoL physical subscales. This analysis demonstrates validity of TIBI-CaP in CRPC pts.
Efscalefect of lenalidomide, bortezomib, and dexamethasone (RVD) induction therapy in transplant-eligible patients (Pts) with newly diagnosed multiple myeloma (MM) on CR rates and survival.
Authors: Charise Gleason, Ajay K. Nooka, Samatha Muppidi, Leonard T. Heffner, Conor E Steuer, Mukesh Kumar, Daniela Casbourne, Amelia A. Langston, Melanie Watson, Lawrence Boise, Jonathan L. Kaufman, Sagar Lonial
Journal: Journal of Clinical Oncology (2012)

8101 Background: Addition of lenalidomide to bortezomib and dexamethasone (RVD) demonstrated to be an effective and well tolerated regimen in phase II trials with overall response rate (ORR) &gt;95% (Richardson P et al). Given the lack of phase III data, we have evaluated our institutional experience of pts treated with RVD induction therapy, to support this triplet combination. Methods: 286 transplant-eligible pts with newly diagnosed MM were treated with RVD induction therapy [R - 25 mg/day (days1–14), V - 1.3 mg/m2 (days 1, 4 8, 11) and D - 40 mg once/twice weekly as tolerated every 21 days] from January 2008 until January 2012. 148 pts underwent ASCT and 138 pts opted for delayed transplant. Post-ASCT 56% pts are on maintenance therapy tailored to their risk (R-40%; RVD-10%; V-6%). Demographic and outcomes data for the pts that underwent ASCT were collected and responses were evaluated per IMWG Uniform Response Criteria. Results: Median age of the pts is 60 years (range 32-77). Other pt characteristics include: M/F 55%/45%; ISS I/II/III 40%/30%/30%; Isotype IgG/IgA/FLC/IgM 61%/20%/18%/1%; high risk/standard risk 13%/87%. Pts received a median of 4 cycles (2-9) of RVD. Median CD34+ stem cell collection was 11.24 x 10 6 /kg. 18% pts required dose reductions (R/V/D-5%/9%/2%) and discontinuation in 2% pts for progressive disease. 49%/8% pts had G1-2/G3-4 PN. Median estimated PFS is 47 months and median OS has not been reached. Response rates are included in the table. Conclusions: RVD is an active induction regimen with superior response rates of &gt; 80% ≥VGPR rates post-ASCT and is well tolerated in newly diagnosed MM pts. Incorporation of lenalidomide did not impact the stem cell collection. Until phase III data are available, our institutional experience could provide a perspective in the choice of RVD as an effective induction regimen in improving ORR and prolonging survival. [Table: see text]