tbuckley/cabot-search huggingface dataset:
Quality of life EQ-5D results from the AETHERA trial: A phase III study of brentuximab vedotin consolidation following autologous stem cell transplant for HL.
Authors: Scott David Ramsey, Auayporn Nademanee, Tamás Masszi, Jerzy Holowiecki, Muneer Abidi, Andy I. Chen, Patrick J. Stiff, Simonetta Viviani, Yanyan Zhu, Vijayveer Bonthapally, Elizabeth Thomas, Naomi N. H. Hunder, Jan Andrzej Walewski
Journal: Journal of Clinical Oncology (2015)

6568 Background: The AETHERA trial demonstrated that early consolidation treatment with brentuximab vedotin (BV) post-ASCT significantly improved PFS in pts with HL. Peripheral neuropathy (PN) was the most common adverse event. Here, we report the results of the Quality of Life (QoL) component of the trial. Methods: After ASCT, 329 pts were randomized to BV 1.8 mg/kg q3wk or placebo for up to 16 cycles. The EQ-5D questionnaire, including the descriptive system and visual analog scale (VAS), was administered at each cycle, end of treatment (EOT), and q3 mos during follow up until 24 mos from Day 1. Utility index value scores were calculated using the time trade-off (TTO) method for US- and UK-based value sets. Differences between arms were compared to the lower bound of an estimated minimally important difference (MID) in cancer pts (Pickard et al 2007). Results: In both arms, EQ-5D scores declined from baseline to 24 mos. Slightly lower scores were seen with BV vs placebo from mos 9-18, but this resolved by end of follow up. In the analysis as randomized (US TTO), the difference between arms was <0.06 (MID) at all timepoints except for mos 15 and 18. Scores by cycle were similar in the 2 arms; mean differences did not reach the MID threshold. In both arms, scores for pts with PD per investigator were lower over time vs. pts with no PD. In the BV arm, scores for pts reporting PN were similar to those who did not. Similar results were obtained with US- or UK-based value sets. EQ VAS scores did not show an important difference between arms at any timepoint. Conclusions: As assessed using the EQ-5D questionnaire, treatment with BV did not have a sustained impact on QoL in HL pts. In both arms, decreased QoL was observed after progression. Clinical trial information: NCT01100502.US-indexed EQ-5D TTO scores. BV N=165 Placebo N=164 BV-placebo Mean Mean Mean Difference (95% CI) Baseline 0.897 0.907 -0.010 (-0.035, 0.014) 3 mos 0.869 0.884 -0.014 (-0.048, 0.019) 6 mos 0.868 0.872 -0.004 (-0.041, 0.032) 9 mos 0.816 0.860 -0.043 (-0.087, 0.001) 12 mos 0.799 0.859 -0.059 (-0.109, -0.010) 15 mos 0.782 0.852 -0.071 (-0.126, -0.015) 18 mos 0.776 0.837 -0.061 (-0.121, 0.000) 21 mos 0.783 0.814 -0.029 (-0.094, 0.037) 24 mos 0.757 0.787 -0.030 (-0.102, 0.042)
Toxicity, quality of life outcomes, and dosimetric impact in phase III trial of hypofractionated or standard fractionated proton therapy for low-risk prostate cancer patients: PCG GU 002.
Authors: Matthew Q. Schmidt, Carlos E. Vargas, William F. Hartsell, Megan Dunn, Sameer R. Keole, Lucius Doh, John Han-Chih Chang, Christopher Sinesi, Gary L. Larson
Journal: Journal of Clinical Oncology (2017)

48 Background: The purpose of this study is to identify differences in toxicity, quality of life (QOL), and dosimetric endpoints among patients with low-risk prostate adenocarcinoma treated with either standard fractionation or hypofractionation proton-beam therapy. Methods: We analyzed the results of the first 75 patients treated in our phase III trial comparing 38Gy relative biological effectiveness (RBE) in 5 fractions (fx) (n = 46) vs. 79.2Gy (RBE) in 44 fx. (n = 29). All patients had low-risk prostate cancer and were treated with proton radiation using fiducial markers and daily image guidance. We evaluated American Urological Association (AUA) Symptom Index, adverse events (AEs), and Expanded Prostate Index Composite (EPIC) domains at pretreatment and 3, 6, 12, 18, 24, 36 and 48 months. Doses to the prostate were selected based on similar long term effects to normal tissue based on an α/β = 3.5 for an EQD2 of 76Gy. Results: The median follow-up was 36 months for both groups; 23 (30%) patients reached a follow-up of 48 months. We observed a small difference in AUA score (3.2 vs. 8.6, p = 0.002) at 1-year favoring the 79.2Gy arm. AUA scores were not statistically different at 18 months and after. Similarly, EPIC Urinary symptoms favored the 79.2Gy arm at 1 year (92.3 vs. 84.5, p = 0.009) and 18 months (92.3 vs. 85.3, p = 0.03); bother scores were not significantly different at any other time points. G2 or higher GU toxicity was similar between arms (p = 0.8). No differences in EPIC Bowel symptoms, EPIC Sexual symptoms, or bowel G2 or higher toxicities were seen. One death was observed in the 38Gy arm due to an unrelated case of multiple myeloma. The bladder V80 (79.2Gy arm, p = 0.04) and V39 (38Gy arm, p = 0.05) were predictive for G2 or higher GU AE. There was no association observed between rectal dose and G2 or higher rectal toxicity. Conclusions: Patients treated in the hypofractionated and standard arms tolerated treatment well. A small and temporary difference in the GU domain was seen favoring the standard arm. As predicted long term effects on the GU domain and bowel were similar for both arms, suggesting that the α/β is similar to 3.5 for long term effects. Clinical trial information: 01230866.
Impact of pharmacist-led monitoring of olaparib (O) for metastatic castrate resistant prostate cancer (mCRPC).
Authors: Andrea McNatty, Elizabeth Dow, Alan Haruo Bryce
Journal: Journal of Clinical Oncology (2017)

e569 Background: O is a PARP inhibitor that has received breakthrough designation for use in mCRPC based on a study in which a subset of 16 patients with DNA repair defects had an 80% response rate. O is an oral tablet taken twice daily. Studies have demonstrated that compliance with oral agents is often poor, and the less frequent contact with medical staff increases the risk of toxicities when compared to IV therapies. This is compounded by a bias where oral medications are thought of as less toxic than IV medications. The toxicities of O include myelosuppression, nausea, vomiting, and fatigue. Our practice employs a pharmacist to conduct weekly phone calls for toxicity management, monitor patient adherence, and monitor for drug-drug interactions. We report our experience with patient adherence, toxicities, and response with O in mCRPC. Methods: A single institution, retrospective review was performed on 14 mCRPC patients treated with O from November 2015 - October 2016. Adherence and toxicity data were assessed and documented via phone calls conducted by a clinical pharmacist. The primary outcomes were number of missed doses, incidence of toxicities, and dose modifications. The secondary outcome was response rate, defined as a 50% reduction in PSA or radiographic response according to RECIST 1.1 for a duration of greater than 3 months. Results: Patients reported taking 99% of the prescribed doses. The toxicities observed most commonly were fatigue (64%), nausea (57%) and anemia (57%). As a result of toxicities, four patients required a dose reduction to 300 mg BID, three patients required a dose reduction to 200 mg BID and two patients were initiated on 200 mg BID and maintained on that dose until progression. Partial responses were seen in 6 of 14 patients. Conclusions: Our pharmacist led adherence program facilitated timely dose adjustments and high patient adherence. Response rates were comparable to published data.
A survey of medical oncologist’s opinions and perceptions regarding the management of dermatologic toxicities among mCRC patients treated with panitumumab in the United States.
Authors: Kimberly Lowe, Rachel Bergstresser, Kristina Hool, George Kafatos, Tamer Garawin, Michelle McNamara, Michael Anthony Kelsh, Seth Collins, Bruce A. Bach
Journal: Journal of Clinical Oncology (2017)

639 Background: Dermatologic toxicity can be a limiting factor for the use of anti-EGFR therapy such as panitumumab. There is a paucity of real world data regarding the management of dermatologic toxicity among metastatic colorectal cancer (mCRC) patients treated with panitumumab in the United States (U.S.). The objective of this study is to describe oncologist's opinions regarding timing of skin rash management in relation to the initiation of treatment and perceptions regarding rash management strategies. Methods: A total of 125 oncologists were recruited from a national database via a third independent party. Eligible oncologists (i.e.: licensed and practicing oncologist who had treated at least three new or continuing mCRC patients with panitumumab in the last year) completed an online survey to report their opinions regarding the grade and type of dermatologic toxicities seen and their perceptions about management strategies for mCRC patients who are treated with panitumumab. The timing of rash management initiation was defined as pre-emptive (prior to the appearance of the rash) or reactive (after any signs of skin rash). Results: Based upon their collective experience, oncologists expect that 44% of patients will develop acneiform rash while on treatment. More than half (58%) of the oncologists reported they did not follow any practice guidelines regarding the management of dermatologic toxicities. The oncologists reported that they pre-emptively initiated the management of dermatologic toxicities in 53% of their patients. Skin moisturizer and sunscreen were reported to be the most critical preemptive management approach, while skin moisturizer, over-the-counter topical steroids, and oral antibiotics were reported to be the most critical reactive management tools for Grades 1, 2, and 3, respectively. Conclusions: Despite evidence from randomized controlled trials, a majority of oncologists do not follow guidelines for dermatologic management of EGFR-I rash. There is a clear need for better physician education and awareness of mitigation strategies for skin toxicity management in mCRC patients treated with panitumumab.
Quality of life (QL) of patients (pts) treated for muscle invasive bladder cancer (MIBC) with radiotherapy (RT) +/- chemotherapy (CT) in the BC2001 trial (CRUK/01/004): Analysis of impact of treatment at an individual level.
Authors: Robert Anthony Huddart, Emma Hall, Miguel Miranda, Malcolm Crundwell, Peter Jenkins, Christine Lisa Rawlings, Jean Tremlett, Carey Hendron, Rebecca Lewis, Nuria Porta, Syed A. Hussain, Nicholas D. James
Journal: Journal of Clinical Oncology (2017)

292 Background: BC2001 showed that adding 5FU+MMC CT (cRT) to RT significantly improved locoregional disease free survival [James 2012] &amp; using reduced high dose volume RT (RHDVRT) rather than standard RT (stRT) did not reduce late side effects [Huddart 2013]. Here we report the impact of treatment on QL at the individual level. Methods: 458 (pts) were randomised to RT (178) vs. cRT (182) (CT comparison) &amp;/or to stRT (108) vs. RHDVRT (111) (RT comparison). Pts completed Functional Assessment of Cancer Therapy-Bladder (FACT-BL) questionnaires at baseline (bl), end of treatment (EoT), 6, 12, 24, 36, 48 &amp; 60 months (m). Mean changes from bl were compared between randomised groups. A minimal clinically relevant change from bl score was defined as 3 points in bladder cancer subscale (BLCS) &amp; 7 points in total FACT-BL (TOTAL). The proportion of pts with an improvement, no difference &amp; worsening at 12m were compared by Chi squared/Fishers exact test (1% significance). Results: Data were available for 331 (92%) &amp; 204 (93%) pts at bl &amp; 181 (50%) &amp; 107 (49%) at 12m for the CT &amp; RT comparison respectively. QL scores were significantly reduced at EoT but recovered to bl levels by 12m with no significant difference in TOTAL or BLCS mean change scores between randomised groups. By EoT ~60% pts reported worsening of QL. At 12m &amp; beyond, whilst mean change scores were not different to bl, ~30-40% reported worsening of QL (-) with a similar proportion reporting an improvement (+) (Table 1). No statistically significant differences were found between randomised groups. Conclusions: Following (c)RT a significant proportion of pts have a decline in QL at EoT but after 12m overall QL is, on average, similar to bl. At an individual level approximately equal proportions of pts report an improvement in QL as report a worsening. There is no evidence of additional impairment in QL by the addition of CT to RT. Clinical trial information: ISRCTN6832433. [Table: see text]
Erratum: ACC/AHA 2002 guideline update for the management of patients with chronic stable Angina - Summary article: A report of the American College of Cardiology/American Heart Association task force on practice guidelines (Committee on the management of patients with chronic stable Angina) (Circulation (January 7-14, 2003) 107 (149-158))
Authors: Gibbons, Jonathan Abrams, Kanu Chatterjee, Jennifer Daley, Prakash C. Deedwania, John S. Douglas, T. Bruce Ferguson, Stephan D. Fihn, Theodore D. Fraker, Julius M. Gardin, Robert A. O'Rourke, Richard C. Pasternak, Sankey V. Williams, Joseph S. Alpert, Elliott M. Antman, Loren F. Hiratzka, Valentin Fuster, David P. Faxon, Gabriel Gregoratos, Alice K. Jacobs, Sidney C. Smith
Journal: Circulation (2003)
Racial disparities in treatment patterns and clinical outcomes in patients (pts) with HER2+ metastatic breast cancer (MBC).
Authors: Adam Brufsky, Denise Aysel Yardley, Marianne Ulcickas Yood, Debu Tripathy, Peter Andrew Kaufman, Musa Mayer, Shibao Feng, Oyewale O. Abidoye, Hope S. Rugo
Journal: Journal of Clinical Oncology (2012)

1526 Background: Data examining prognosis and treatment outcomes for black pts with HER2+ MBC are limited. Methods: registHER is a large, observational cohort of pts (N=1,001) with HER2+ MBC diagnosed w/in 6 mos of enrollment and followed until death, disenrollment, or 6/09 (median follow-up 27 mos). Demographics, treatment patterns, and clinical outcomes were described for black (n=126) and white pts (n=793). Progression Free Survival (PFS) and Overall Survival (OS) were examined. Multivariate analyses adjusted for baseline and treatment factors. Results: Black pts were more likely to be obese (BMI ≥ 30), have diabetes, and a history of cardiovascular disease (CVD) than white pts (Table). Black pts were less likely to have estrogen receptor (ER)/progesterone receptor (PR)+ disease and more likely to present with stage IV MBC. In trastuzumab (T)-treated pts, incidence of cardiac safety events (grade ≥3) was higher in black (13/119 [10.9%]) than white pts (59/746 [7.9%]). Unadjusted median OS (mos) was significantly lower (blacks: 27.1, 95%CI 23.2-32.1; whites: 37.3, 95%CI 34.6-41.1) and median PFS (mos) was lower (blacks: 7.0, 95%CI 5.7-9.7; whites: 10.2, 95%CI 9.3-11.2) in black than white pts. The adjusted OS hazard ratio (HR) for black vs. white was 1.32 (95%CI 1.04, 1.69); the adjusted PFS HR was 1.31 (95% CI 1.07, 1.61). Conclusions: These population-based data show poorer prognostic factors and independently worse clinical outcomes in black vs. white pts, and represent the largest database to date with black pts with HER2+ MBC. Further research is needed to explore the basis for the differences noted in this hypothesis-generating analysis. [Table: see text]
PREDICTING THE OUTCOME OF SEVERE VARICEAL GASTROINTESTINAL BLEEDING
Authors: Mohammad A. Al-Freah, Amit Gera, Silvia Martini, Debbie L. Shawcross, Daniel Abees, Nicholas J. Taylor, Georg Auzinger, Phillip M. Harrison, John Devlin, Michael A. Heneghan, Nigel Heaton, William Bernal, Julia Wendon
Journal: Hepatology (2010)
Utilization of systemic therapy options in the routine treatment of metastatic colorectal cancer.
Authors: Rachel Lee Delahunty, Margaret Lee, Hui-Li Wong, Joseph James McKendrick, Belinda Lee, Suzanne Kosmider, Prasad Cooray, Sumitra Ananda, Ben Tran, Jeanne Tie, Jayesh Desai, Peter Gibbs, Rachel Wong
Journal: Journal of Clinical Oncology (2017)

738 Background: In the treatment of metastatic colorectal cancer (mCRC), exposure to all three active cytotoxic agents; 5-fluorouracil/capecitabine (FP), irinotecan (Ir) and oxaliplatin (Ox), and the biologic agents, bevacizumab (Bev) and cetuximab and panitumumab (EGFR-I) improves outcomes. The current uptake of systemic agents for mCRC in a community setting in Australia is poorly described. Methods: The ACCORD database was interrogated to determine demographics, treatments and outcomes for all patients diagnosed with mCRC between 1/01/2011 and 1/01/2015 at 6 Melbourne centres (3 public and 3 private). Results: 865 patients were identified: median age was 68 years. 68% were ECOG 0-1, 60% had de novo metastatic disease. RAS status was known in 59%, of whom 48% were RAS wild-type (WT). At the time of analysis 69% of all patients had received systemic treatment with 51% receiving treatment second line and beyond; 65% RAS WT, 57% RASm, 16% RAS-Unk. See Table. Metastasectomy was performed in 29% of patients of whom 38% remain disease-free. With a median follow-up of 31.3 months 46% of patients remain alive. The median overall survival was 25 months for all patients(unresected;17.6 months, resected: not reached). Conclusions: A high proportion of patients receiving routine clinical care in the community setting do not receive any systemic therapy and few patients receive all available active agents. Despite this, the overall survival of patients with mCRC in this community-based cohort was 25 months and in-line with clinical trial data. [Table: see text]
Evaluation of pharmacokinetic (PK) drug-drug interactions (DDI) between trebananib (AMG 386) and paclitaxel (PTX) in patients (pts) with advanced solid tumors.
Authors: Jennifer Robinson Diamond, Neeraj Agarwal, Daniel W. Bowles, Elaine Tat Lam, Theresa Louise Werner, Benjamin Wu, Erik Rasmussen, Erick Gamelin, Felipe Soto, Gregory R. Friberg, Yu-Nien Sun, Sunil Sharma
Journal: Journal of Clinical Oncology (2014)

2584 Background: Trebananib (AMG 386) is an investigational peptide-Fc fusion protein that inhibits angiogenesis by preventing the interaction between angiopoietin-1/2 and Tie2. In a phase 3 study, trebananib 15 mg/kg QW plus PTX improved progression-free survival in women with recurrent ovarian cancer compared with placebo plus PTX. PTX was chosen because it is a standard of care in ovarian cancer, and both PTX and trebananib are dosed weekly. This open-label phase 1b DDI study evaluated PK of PTX with/without trebananib. Methods: Pts with advanced solid tumors who were candidates for PTX treatment, had evaluable/measurable disease per RECIST v1.1, and ECOG performance status ≤2 received PTX 80 mg/m2 IV QW (3 wks on/1 wk off) beginning wk 1 and trebananib 15 mg/kg IV weekly QW beginning wk 2 until disease progression, unacceptable toxicity, or withdrawal of consent. Intensive PK sampling occurred in wks 1 (PTX only), 6 (PTX+trebananib), and 8 (trebananib only). CT/MRI was performed every 8±1 wks. The primary endpoint was Cmax/AUC of PTX with/without trebananib. Results: Thirty-five pts were enrolled. Most had ovarian (n=11) or bladder cancer (n=9). Mean PTX Cmax and AUCinf were similar with/without trebananib, and mean trebananib Cmax,ss and AUCtau,ss were similar with/without PTX (Table). All pts had ≥1 adverse event (AE), most commonly fatigue (any grade/grade 3 or 4, 57%/14%), nausea (54%/3%), peripheral edema (51%/6%), and peripheral neuropathy (46%/3%). 34% of pts discontinued trebananib due to AEs. Among 26 pts with measurable disease, 5 had partial response and 8 had stable disease (per RECIST) as best response. Conclusions: There was no evidence of clinically meaningful PK DDI between trebananib and PTX. Toxicity was as anticipated for the combination of trebananib plus weekly PTX; no new toxicity signals were identified. Clinical trial information: NCT01992341.PK of paclitaxel and trebananib. Paclitaxel Week 1 PTX alone Week 6 PTX + trebananib n Mean SD n Mean SD Cmax, ng/mL 33 2,290 896 30 2,970 932 AUCinf, ng•h/mL 33 5,200 1,590 29 6,240 1,820 Trebananib Week 6 PTX + trebananib Week 8 Trebananib alone n Mean SD n Mean SD Cmax,ss, µg/mL 31 359 98.2 28 366 90.6 AUCtau,ss, mg•h/mL 31 15.4 5.64 28 17.0 6.97
Use of adjuvant chemotherapy and outcomes in women age 70 and older with HER2-positive (HER2+) or triple-negative (TN) breast cancer (BC).
Authors: Tina Hsu, Caroline Speers, Scott Tyldesley, Stephen K. L. Chia
Journal: Journal of Clinical Oncology (2013)

1044 Background: Chemotherapy use decreases with increasing age. There is a stronger rationale for adjuvant chemotherapy in HER2+ and TN BC due to a higher risk of recurrence, known benefit of trastuzumab with chemotherapy and lack of other systemic options. Aims: 1) Characterize and compare outcomes of resected HER2+/TN BC in older women (age ≥70) (OW) vs. younger women (age 50-69) (YW) 2) Determine chemotherapy use in OW vs. YW 3) Compare outcomes in OW based on receipt of chemotherapy. Methods: Women ≥ 50 years old with newly diagnosed resected HER2+ or TN stage I-III BC in British Columbia between 2003 and 2006 were included. Demographic, prognostic and treatment characteristics were compared in OW vs. YW using Chi-Square and t-tests. Kaplan-Meier curves for relapse-free survival (RFS), breast cancer-specific survival (BCSS) and overall survival (OS) were calculated in the various cohorts. Results: OW (n=292) had larger tumors (p=0.002), more often had mastectomy and less often had adjuvant radiation (p&lt;0.001) than YW (n=946). There were no differences in nodal or receptor status. OW vs. YW were less likely to receive chemotherapy (28.1 vs. 81.3%, p&lt;0.001); odds decreased with increasing age (OR 15.9 and 7.4 for women age 50-59 and 60-69 vs. ≥70, p&lt;0.001). OW had worse 5-year RFS (75.4 vs. 83.2%, p=0.002), local RFS (93.2 vs. 95.5%, p=0.05) and distant RFS (77.5 vs. 85.5%, p=0.001). Both 5-year BCSS (79.5 vs. 88.1%, p&lt;0.001) and OS (63.7 vs. 85.8%, p&lt;0.001) were worse in OW vs. YW. OS, but not BC-specific outcomes (RFS, BCSS), was significantly better in those who received chemotherapy compared to those who did not (Table). Conclusions: OW with HER2+ and TN BC are less likely to receive adjuvant chemotherapy than YW. No difference in BCSS was noted in OW based on receipt of chemotherapy, possibly due to a small sample size. Differences in OS based on receipt of adjuvant chemotherapy suggest that oncologists in British Columbia are accurately identifying women with limited life expectancy less likely to benefit from chemotherapy. [Table: see text]