bluuebunny/crossref_metadata_2025 huggingface dataset:
Subgroup analysis of crizotinib versus either pemetrexed (PEM) or docetaxel (DOC) in the phase III study (PROFILE 1007) of advanced ALK-positive non-small cell lung cancer (NSCLC).
Authors: Solomon Benjamin J. , Gettinger Scott N. , Riely Gregory J. , Gadgeel Shirish M. , Nokihara Hiroshi , Han Ji-Youn , Hida Toyoaki , Satouchi Miyako , Baldini Editta , Siena Salvatore , Yamamoto Nobuyuki , Horn Leora , Tassell Vanessa Roberts , Polli Anna , Camidge D. Ross
Published: March 2020

8105

Background: PROFILE 1007 compared the efficacy and safety of crizotinib with that of standard-of-care chemotherapy in patients with ALK+ NSCLC. Although the study was not designed for formal assessment of patient outcomes on crizotinib vs. PEM or crizotinib vs. DOC, due to later interest, we performed retrospective efficacy and safety analyses of patient subgroups treated with crizotinib or each chemotherapy individually. Methods: Patients with stage IIIB/IV ALK+ NSCLC previously treated with 1 prior platinum-based regimen were randomized to receive crizotinib 250 mg PO BID or chemotherapy (PEM 500 mg/m2 or DOC 75 mg/m2, IV q3 wk). Patients with progressive disease on chemotherapy were offered crizotinib treatment in a separate study. In these subgroup analyses, PFS and ORR based on independent radiologic review, and safety were evaluated. Results: Of 347 patients randomized, 172 received crizotinib, 99 PEM, 72 DOC, and 4 no treatment. At data cutoff (Mar 2012), 85 crizotinib patients, 21 PEM patients, and 7 DOC patients were receiving treatment. Median treatment duration was longer in the crizotinib arm (7.1 mo) than in either the PEM (4.1 mo) or DOC (2.1 mo) treatment subgroups. Median PFS was significantly longer on crizotinib (7.7 mo) than on either PEM (4.2 mo; HR, 0.59; P=0.0004) or DOC (2.6 mo; HR, 0.30; P<0.0001). 1-year PFS rates were 31% on crizotinib, 16% on PEM, and 6% on DOC. The ORR on crizotinib (66%) was significantly higher than on either PEM (29%; risk ratio, 2.31; P<0.0001) or DOC (7%; risk ratio, 9.65; P<0.0001). The most common all-causality adverse events with crizotinib were diarrhea (60%), vision disorder (60%), and nausea (55%); with PEM, nausea (38%), fatigue (36%), and decreased appetite (26%); and with DOC, alopecia (47%), neutropenia (43%), and nausea (36%). Conclusions: Crizotinib’s superior efficacy over chemotherapy, with a distinct but generally tolerable and manageable side effect profile in patients with advanced ALK+ NSCLC, was also observed in separate comparisons with either PEM or DOC. In patients receiving chemotherapy, median PFS, 1-year PFS rates, and ORR were all numerically higher on PEM than on DOC. Clinical trial information: NCT00932893.
Clinical implications of routine testing for epidermal growth factor receptor (EGFR) mutations in patients with nonsquamous non-small cell lung cancer (NSCLC).
Authors: Zhu Hui , Arrossi Andria Valeria , Elson Paul , Farver Carol , Tubbs Raymond R. , Murthy Sudish C. , Mason David P. , Mazzone Peter J. , Pennell Nathan A.
Published: March 2020

8113

Background: EGFR mutation (Mut) testing is recommended for all patients (pts) with advanced NSCLC to identify pts who may benefit from front-line EGFR tyrosine kinase inhibitor (TKI) therapy. In July 2010 the Cleveland Clinic initiated reflex EGFR testing of all new diagnoses of nonsquamous NSCLC, prior to which testing was done only by physician request. A retrospective study was designed to review how this change affected clinical practice in a large academic health center. Methods: All pts with NSCLC that had EGFR Mut testing performed at the Cleveland Clinic from 07/2009 to 02/2012 were included (n=287). Pt characteristics, tumor histology and stage, Mut status, treatments, and pt outcomes were collected from electronic medical records. Special attention was given to pts with EGFR Mut+ who received erlotinib (E). Data were analyzed using Fisher’s exact, chi-square and the Wilcoxon rank-sum tests. Results: See Table. Conclusions: Automatic EGFR mutation testing, recommended in an ASCO provisional clinical opinion in April 2011, was feasible in a large academic center and significantly shortened the time between diagnosis and EGFR status becoming available to guide treatment decisions. Although not statistically significant due to the small sample size, there were positive trends towards increased first line usage of E in pts with EGFR Mut+, better performance status, lower rates of E discontinuation due to toxicity, and higher response rate to E in the automatic testing group. There was no difference in overall survival between the two groups. [Table: see text]
Erlotinib beyond progression study: Randomized phase II study comparing chemotherapy plus erlotinib with chemotherapy alone in EGFR tyrosine kinase inhibitor (TKI)-responsive, non-small cell lung cancer (NSCLC) that subsequently progresses.
Authors: Halmos Balazs , Pennell Nathan A. , Otterson Gregory Alan , Gadgeel Shirish M. , Mekhail Tarek , Snell Michael Robert , Kuebler J. Phillip , Fu Pingfu , Sharma Neelesh , Dowlati Afshin
Published: March 2020

8114

Background: In EGFR-TKI responsive NSCLC, at progression only some tumor clones might carry resistance mechanisms. This provides a rationale for maintenance therapy with TKIs on progression and is supported by “tumor flares” noted in patients taken off of TKI therapy. Methods: Randomized, phase II study of chemotherapy (pemetrexed or docetaxel) versus chemotherapy plus erlotinib (ERL) in patients with progressive NSCLC following clinical benefit from erlotinib for > 12 weeks. In Arm A Pemetrexed or Docetaxel were given at standard doses every 3 weeks to a maximum of 8 cycles. In Arm B chemotherapy was given with ERL at 150 mg oral daily dose on days 2-19 of each cycle. The primary endpoint was that continuation ERL in this patient population could extend PFS by 50%, from 3 to 4.5 months. The original enrollment goal was 39 pts per arm to allow 80% power to detect such a difference. Results: 46 patients were randomized (Arm A: 24; Arm B: 22). Early termination was due to slow enrollment. Patient characteristics were well balanced except for more females on Arm A (p=0.075). The median PFS on Arm A was 5.4 months and for Arm B was 4.6 months (p=0.569). The median overall survival (OS) on Arm A was 18.7 months and for Arm B 14.7 months (p=0.295). Multiple Cox regression analysis showed an impact of female gender on OS (HR 0.1) but not PFS (HR=0.49). EGFR status was available on 39/46 patients. 17 patients in Arm A and 14 Arm B were mutation positive. In analyzing mutation + only patients, no difference in PFS (p=0.332) or OS (p=0.346) was seen amongst the 2 groups. In the mutation + patients the 6 months PFS for Arm A was 39% and for Arm B was 32%. More toxicity was seen on Arm B as compared to Arm A. Irrespective of causal attribution, 1 grade 5 event occurred on Arm A as opposed to 2 events on Arm B. A total of 7 grade 3/4 events occurred on Arm A while 24 occurred on Arm B. Conclusions: No benefit was seen with the continuation of ERL in addition to chemotherapy as compared to chemotherapy alone in patients who had previously benefited from ERL but then showed progression. The combination arm showed significantly more toxicity. Clinical trial information: NCT00660816.
A multicenter, randomized, double-blinded, placebo-controlled trial of modafinil for lung cancer-related fatigue: Dose response and patient satisfaction data.
Authors: Fife Kate , Spathis Anna , Dutton Susan J. , Blackhall Fiona Helen , Bahadori Ronja , Wharton Rose , O'Brien Mary , Stone Patrick , Benepal Tim , Wee Bee
Published: March 2020

9503

Background: Fatigue is a very common, disabling symptom in cancer, and particularly severe in lung cancer. Modafinil is a novel central nervous system stimulant, which, along with methylphenidate, is cautiously recommended by the 2013 National Comprehensive Cancer Network Guidelines for fatigue. In this phase IV randomized placebo-controlled trial, we assessed the efficacy of modafinil for managing fatigue in lung cancer. Methods: Adults with locally advanced or metastatic non small cell lung cancer (stages III and IV), ECOG performance status (PS) 0-2 and suffering from fatigue (score 5/10 or greater) were randomised 1:1 to modafinil or matched placebo, 100mg daily for 14 days and 200mg daily for a further 14 days. The primary outcome measure was change in the Functional Assessment of Chronic Illness Therapy fatigue subscale (FACIT-fatigue) at 28 days. The trial was powered to detect a 5-point difference with 80% power and 5% significance allowing for 25% attrition. Dose-response, patient satisfaction and safety were also evaluated. Results: 208 patients were recruited from 24 UK centres. Baseline characteristics were well-balanced. 160 patients completed both baseline and 28 day questionnaires and were included in the modified-ITT analysis. FACIT-fatigue mean change from baseline was modafinil=5.28, placebo=5.11, difference=0.17, (95%CI -4.17, 3.82). Adjustment for baseline fatigue and PS had no impact on outcome. No dose response was seen; the majority of improvement on all scales was seen at 14 days and sustained to 28 days. 47% of the modafinil group and 23% of the placebo group stated the study treatment was not helpful (p=0.132). Adverse events were equal. Conclusions: Both modafinil and placebo led to a clinically significant 5-point improvement in FACIT-fatigue score, but there was no significant difference between the two groups. This well-powered study suggests that there is a large placebo effect and NCCN guidelines should be reviewed. Clinical trial information: NCT00829322. [Table: see text]
Effect of renal function (RF) on outcomes in the adjuvant treatment of older women with breast cancer (>65 years): CALGB/CTSU 49907 (CC) ancillary data study.
Authors: Lichtman Stuart M. , Cirrincione Constance , Hurria Arti , Jatoi Aminah , Theodoulou Maria , Wolff Antonio C. , Gralow Julie , Morganstern Daniel , Magrinat Gustav , Cohen Harvey Jay , Muss Hyman ,   The Alliance for Clinical Trials in Oncology
Published: March 2020

9515

Background: CC 49907 showed superiority of standard therapy (cyclophosphamide/doxorubicin [AC] or cyclophosphamide/methotrexate/5-fluorouracil [CMF]) over capecitabine[C]. Dose adjustments made for renal insufficiency (RI) for methotrexate and C; ideal body weight used. Purpose was to analyze the relationship between RF at baseline and 5 endpoints: toxicity, dose modification, therapy completion, relapse-free survival [RFS] and overall survival [OS]. Methods: Pre-treatment RF was calculated (Cockcroft-Gault). Endpoints assessed by regimen. RF was tested as a dichotomous and continuous variable of stages 1,2 vs. 3,4 kidney disease (National Kidney Foundation). Logistic regression modeled the relationship between renal stage and the first three endpoints of toxicity, dose modification and therapy completion. Toxicity divided by hematologic or not. The relationship of RFS and OS with RF was assessed with the logrank test and as a continuous variable with Wald chi square. Results: 619 patients; incidence of stage 3/4 RI(<60 ml/min) was: CMF=72%; AC=64%; C=75%. With AC the incidence of toxicity differed by renal function. 31% of patients with poorer function >grade 3 non-hematologic toxicity vs. 14% with better function(p=0.011). There was a suggestion of effect of RF on OS and RFS for C-treated patients. RF was not associated with dose modification, premature therapy termination, RFS or OS for the CMF-treated patients. Conclusions: 1) AC: declining RF was associated with increased non-hematologic toxicity. 2)Patients with RI who received dose modifications were not at increased risk for complications in comparison to those who did not have renal insufficiency and received full dose. 3)Declining RF did not affect therapy completion. 4)C: suggestion that worse RF was related to poorer RFS or OS. 5)Exclusion of patients from clinical trials with RI based on concern of excessive hematologic toxicity may not be justified with appropriate modification. 6)Results should be considered in the design of clinical trials for older patients.
End-of-life care for Medicare beneficiaries with ovarian cancer: Evaluation of intensity and rate of hospitalizations.
Authors: Wright Alexi A. , Earle Craig , Keating Nancy Lynn
Published: March 2020

9523

Background: Patients with advanced cancer are receiving increasingly aggressive medical care at the end-of-life (EOL). Population-based studies have not examined the medical care that ovarian cancer patients receive near death. Methods: We identified a national cohort of 6,956 Medicare beneficiaries who were living in Surveillance, Epidemiology, and End Results (SEER) areas, were diagnosed with epithelial ovarian cancer between 1996 and 2007, and died from ovarian cancer by December 2007. Using multivariable models, we examined rates of aggressive medical care within 30 days of death over time and examined indications for hospitalizations near death. Results: Adjusted rates of intensive care unit (ICU) admissions and emergency department (ED) visits increased significantly between 1996 and 2007 (ICU: 6.4% to 16.6%, p<0.0001 and ≥2 ED visits: 19.7% to 32.1%, p<0.0001). In contrast, late (within 7 days death) or absent hospice referrals decreased (63.1% to 47.8%, p<0.001) and chemotherapy use within 30 days of death decreased slightly (8.1% vs. 7.1%; p=0.04). Although terminal hospitalizations decreased (28.0% to 19.1%, p=0.001), rates of hospitalizations near death increased over time (41.4% vs. 45.3%, p=0.01). The most common indications for hospitalization included: bowel obstructions (20.0%), infections (10.4%), fluid or electrolyte abnormalities (9.2%), and malignant effusions (8.1%). Conclusions: Despite significant increases in the use of hospice near death, utilization of ICUs, EDs, and acute inpatient care at the EOL rose significantly between 1997 and 2007 for older ovarian cancer patients. Future studies should examine whether this high-intensity health care is avoidable given evidence that high-intensity care is associated with lower patient quality-of-life near death and increased complications in bereaved caregivers.
Psychosocial outcomes among bereaved and non-bereaved parents of children with cancer.
Authors: Rosenberg Abby R. , Bradford Miranda , Shaffer Michele , Wolfe Joanne , Baker Kevin Scott
Published: March 2020

9526

Background: Psychosocial outcomes among parents of children with cancer are not well characterized and may affect the well-being of cancer-survivors and other children in the home. In order to examine adverse psychosocial outcomes among bereaved (BR) and non-bereaved (NBR) parents, we conducted a cross-sectional, survey-based study. Methods: Enrolled parents completed the “Resilience in Pediatric Cancer Assessment” (RPCA) at least 6 months after their child completed therapy or died from cancer. The RPCA is comprised of validated instruments to assess resilience, emotional distress, social function, health-related quality of life, and financial hardship. Descriptive statistics were used to characterize groups. Differences between groups were assessed with t or Fisher’s exact tests. Differences between the combined sample and population norms were assessed with one-sample t or binomial tests. Results: 120 (78%) of invited parents completed the RPCA (24 BR; 96 NBR). Compared to the general population, parents had lower levels of self-perceived resilience and higher levels of psychological distress. They were more likely to meet criteria for serious, debilitating psychological distress, or Post-Traumatic Stress Disorder (PTSD). All parents (100%) endorsed at least some PTSD symptoms. Parents also reported less marital satisfaction and family cohesion, and more sleep disturbance and binge drinking than population norms. Conversely, enrolled parents reported higher levels of social support and family adaptability, and were less likely to smoke cigarettes (all p<0.05). Compared to parents of survivors, BR parents were less likely to report appreciation for life, an ability to cope, or deal with stress. They had higher levels of psychological distress, more sleep difficulties, and greater financial hardship (all p<0.05). There were no differences between BR and NBR parents with respect to marital satisfaction, family function, or perceived general health. Conclusions: Parents of children with cancer are at high risk for poor psychosocial outcomes. Compared to parents of survivors, bereaved parents are at additional risk. Interventions aimed at improving resilience and other psychosocial outcomes are needed.
Effect of YOCAS yoga on insomnia and sleep medication usage among breast cancer patients receiving hormone therapy: A URCC CCOP randomized, controlled clinical trial.
Authors: Peppone Luke Joseph , Janelsins Michelle Christine , Peoples Anita Roselyn , Kamen Charles Stewart , Kirshner Jeffrey J. , Gaur Rakesh , Atkins James , Reddy Pavan S. , Mustian Karen Michelle
Published: March 2020

9531

Background: Insomnia (INS) is a highly prevalent side effect of hormonal therapy for breast cancer. Patients often turn to Rx sleep meds, which may lead to negative interactions with cancer therapeutics, dependency, rebound impairment, and do not cure INS. We conducted a secondary data analysis of a multi-site, phase III RCT examining the efficacy of yoga for improving INS and decreasing sleep medication usage among breast cancer patients currently receiving hormone therapy through the University of Rochester Cancer Center Community Clinical Oncology Program (CCOP). Methods: The original RCT randomized patients with any type of non-metastatic cancer without previous yoga participation into 2 arms: 1) standard care monitoring [controls] or 2) 4-week yoga intervention (2x/wk; 75 min/session) plus standard care. The yoga intervention utilized the UR Yoga for Cancer Survivors (YOCAS) program consisting of breathing exercises, 18 Hatha and Restorative yoga postures, and meditation. Only breast cancer patients currently receiving aromatase inhibitors (N = 95) or tamoxifen (N = 72) were included in this analysis. Changes in INS and sleep meds between the groups were assessed using ANCOVA with baseline values as covariates. Results: Despite using Rx sleep meds at baseline, INS, assessed by the Insomnia Severity Index, was worse for those women compared to women not taking any Rx sleep meds (Rx = 15.3 vs No Rx = 13.1; p<0.01). Yoga participants demonstrated greater improvements in INS compared to controls (CS=change score; Yoga CS = −3.3 vs Control CS = −0.5; p<0.01). In addition to improved INS, yoga participants significantly decreased Rx sleep med usage compared to controls (Yoga = −17.6% vs Control = −3.3%; p=0.04). There was also a trend toward lower combined Rx/Non-Rx sleep med use for the yoga group compared to controls (Yoga = −14.5% vs Control = −3.1%; p=0.09). Conclusions: YOCAS yoga is a safe intervention that significantly improves INS while concurrently reducing Rx sleep medication usage among breast cancer patients receiving hormone therapy. Funding: MRSG-13-001-01-CCE, NCI U10CA37420, K07CA120025 and OCCAM supplement. Clinical trial information: NCT00397930.
Pattern of chemotherapy use at end-of-life (EOL) in patients with solid tumors (ST).
Authors: Burke Thomas W. , DeJesus Yvette A , Cheng Lee , Buzdar Aman , Rodriguez Maria Alma
Published: March 2020

9539

Background: Quality performance measures for cancer care, including use of chemotherapy in the last two-weeks of life, will be required for reporting. In this study, we evaluated the pattern and frequency of chemotherapy use for ST patients in the last two-weeks of life, and whether such treatment included standard or investigational drugs. Methods: We conducted a retrospective study of 5,607 adult cancer patients (≥18 years) who received their care at The University of Texas MD Anderson Cancer Center and died between December 01, 2010 through May 31, 2012. Data on patients’ demographics, and chemotherapy agents dispensed (excluded: hormones) were obtained from the institution’s administrative databases. Type of treatment (research versus standard) was obtained from our chemotherapy dispensed database. Chi-square test and Fisher's exact test were used to determine the association between categorical variables.All statistically significant levels were determined with P values < 0.05. Results: Only 3.9% (216/5,607) of ST patients who died had received chemotherapy within 14 days EOL. For those 216 patients who received chemothapy: median age 64 years; 48% female; 89% metastatic disease. The distribution by chemotherapy treatment route: intravenous (IV) 85%; IV plus oral 6%; oral 6%; other 3%. The distribution of patients by number of chemotherapy agents: one 56%; two 31%, and three or more 13%. Among those who received chemotherapy, 98.6% (213/216) of the chemotherapy administered were standard agents. There were no differences in frequency distribution for chemotherapy treatment route (p>0.05), number of chemotherapy agents (p>0.05) between patients with metastatic and non-metastatic disease, or between men and women (p>0.05). Conclusions: Our results indicate EOL chemotherapy use was infrequent in our patients with STs, and most of those treated received standard chemotherapy, with simple one or two drug regimens. We need more research to determine factors that influence chemotherapy use at EOL, and if it palliates physical symptoms and/or emotional distress in advanced stages of disease.
Impact of bladder cancer (BC) on health-related quality of life (HRQL) in 1,476 older Americans.
Authors: Fung Chunkit , Pandya Chintan , Noyes Katia , Scosyrev Emelian , Sahasrabudhe Deepak M. , Messing Edward M. , Mohile Supriya Gupta
Published: March 2020

9549

Background: The impact of BC on HRQL is poorly understood. To our knowledge, this is the first and largest cross-sectional study that compares HRQL of patients before and after BC diagnosis (DX). Methods: Our sample included 1,476 BC patients (≥ age 65) within the SEER-Medicare Health Outcomes Survey linkage database (1998-2007). We assessed differences in HRQL as measured by SF-36 physical (PCS) and mental (MCS) summary scores in patients who had a survey >1 yr before BC DX (n=620) and those who had a survey after BC DX (n=856). We compared groups by year from BC DX using regression analyses and results were adjusted for cancer stage, race, gender, age at BC DX, marital status, education, income, smoking status, activity of daily living (ADLs), and non-cancer comorbidities. Results: Patients who had a survey after BC DX were diagnosed with BC at an older age than those with a survey before BC DX (55.9% at age ≥75 yr vs. 36.8%; P<0.01). Other baseline demographic and socioeconomic characteristics were similar. Baseline HRQL were poor in patients before DX (PCS mean=40.1; MCS mean=51.1) with 50.6% and 31.9% of them having comorbidity score ≥2 and impairment of ≥1 ADLs, respectively. After BC DX, significant decreases in PCS (-2.7; 95% CI -3.8,-1.7) and MCS (-1.4; 95% CI -2.6, -0.3) were observed, with HRQL being lowest in those who had BC DX within 1 yr (PCS mean= 36.6; MCS mean=49.7). Declines in PCS during the <1, 1-3, 3-5, 5-10, and 10+ yr periods after BC DX compared to before BC DX were -3.8 (P<0.01), -2.5 (P<0.01), -2.2 (P=0.01), -1.1 (P=0.19) and -0.8 (P=0.57) whereas decreases in MCS were -2.0 (P=0.01), -2.2 (P<0.01), -1.2 (P=0.21), -0.1 (P=0.92), -0.8 (P=0.62) respectively. More advanced BC, lower educational level, higher comorbidity score, and impaired ADLs were significantly associated with both worse PCS and MCS after BC DX (P<0.05). Lower income and older age at BC DX showed significant association with low PCS (P<0.05). Conclusions: Older BC patients are a vulnerable population with poor baseline HRQL. HRQL of patients after BC DX is significantly worse than HRQL of patients before DX, possibly due to therapy and/or disease progression. Future research that evaluates interventions to improve HRQL in older patients with BC is critical.
Safety and tolerability in patients over age 75 included in phase I: The Institut Gustave Roussy experience.
Authors: Helissey Carole , Roquet Florian , Lanoy Emilie , Varga Andrea , Massard Christophe , Gazzah Anas , Ribrag Vincent , Bahleda Rastislav , Angevin Eric , Deutsch Eric , Soria Jean-Charles , Hollebecque Antoine
Published: March 2020

9556

Background: Safety and tolerability of anti-cancer therapy in elderly people (>=75 years, EP) is of major interest since they represent 31% of US patients diagnosed with cancer. However proportion of EP recruited is only 9% in clinical trials and probably less in phase I trials, which aim to determine the recommended phase II dose. Our objective was to evaluate the safety of phase I trials in EP. Methods: Patients treated from 2007 to 2012 at Institut Gustave Roussy in phase I trials, in which patients aged over 75 years had been included. Population was divided into two groups: EP or patients aged < 75 years (YP). Time to occurrence of first high toxicity (any grade 3-4 adverse event (AE) or dose-limiting toxicity DLT) and overall survival were estimated using Kaplan-Meier method. Conditional Cox proportional hazards model was used to compare occurrence of AE in a sub population of patients aged >= 75 years matched with patients aged <75 years of same Royal Marsden Hospital (RMH) score (Albumin, LDH, Number of metastatic site) and protocol. Results: In the 33 EP and the 161 YP, 20(60%) and 100(62%) grade 3-4 AEs and 1(3%) and 18(11%) DLTs occurred. The median time to occurrence of high toxicity were 2 months (95%CI=1-4) and 2 months (95%CI=1-2). The median overall survival were 22 months (95%CI=11-non estimable) (EP) and 13 months (95%CI =10-16) (YP). Twenty-seven patients aged >=75 years could be matched: age over 75 years was not associated with higher risk of neither high toxicity (HR=0.85, 95%CI=[0.45 ; 1.61], p=.62) nor death (HR=1.03, 95%CI=[0.47;2.24], p=.94). Conclusions: No impact of age over 75 years on occurrence of neither high toxicity nor death was identified. Patients above 75 years are good candidates for phase I trials.
Epoetin biosimilars in the management of anemia secondary to chemotherapy in patients with solid tumors, lymphomas, and myelomas: The ORHEO study.
Authors: Luporsi-Gely Elisabeth , Soubeyran Pierre-Louis , Michallet Mauricette
Published: March 2020

9564

Background: Chemotherapy may induce anemia with potentially severe consequences. The ORHEO (place of biOsimilaRs in the therapeutic management of anaemia secondary to chemotherapy in HaEmatology and Oncology) study examined the efficacy and safety of epoetin alfa biosimilars (EABs) for the treatment of chemotherapy-induced anemia (CIA) in the clinical setting. Methods: ORHEO was a multicenter, observational, prospective, post-marketing study conducted in France. Patients with CIA (Hb <110g/L) >18 years old, with solid tumors, lymphomas or myelomas and eligible for epoetin alfa treatment were included in the study; they received EAB as prescribed by their physician. Baseline patient characteristics and anemia-related data including baseline and target Hb level epoetin treatment, adverse events and any other concomitant treatments prescribed were recorded. The primary endpoint was the rate of responders (defined as an increase in Hb levels to 100 g/L or at least 10 g/L since inclusion visit, or reaching target Hb set at start of study, without any blood transfusions in the 3 weeks prior to measurement) at +3 months (M3). Other endpoints included rate of responders at +6 months (M6) and safety endpoints. Results: 2310 patients (51.43 % male, 48.57 % female) from 232 centers were included in this study. At baseline 79.6% had solid tumors, 13.0% lymphomas and 7.4% myelomas. Median age was 68 y (range: 18–93). Mean baseline Hb level was 96 g/L with a target Hb level of >= 120 g/L for 52.7% of patients. Almost all (99.9%) received the biosimilar epoetin zeta (median dose 30,000 IU/week) with 26.6% receiving additional iron supplementation. A total of 2056 and 1664 patients had at least one Hb level value at M3 and M6 respectively. The rate of response was 81.6% and 86.5% at M3 and M6, respectively. In total, 17.0% of treated patients reported clinically relevant adverse events (all grades), the most common being infections (5.0%) and thromboembolic events (3.5%). Transfusion rates were reported as 9.4% and 5.8% at M3 and M6, respectively. No EAB-related deaths were reported. Conclusions: EAB was effective and well-tolerated in the management of CIA. Clinical trial information: NCT01626547.
Practical assessment of psychosocial concerns associated with genetic testing in ovarian cancer patients using the MICRA questionnaire.
Authors: Bjørnslett Merete , Dahl Alv A. , Sørebø Øystein , Dørum Anne
Published: March 2020

9569

Background: Ten to 15% of ovarian cancer patients are BRCA mutation carriers. By offering genetic testing, families at risk and healthy female mutation carriers will be identified and offered clinical follow-up. The MICRA questionnaire was developed as a brief, practical, and targeted assessment of concerns and psychosocial issues associated with genetic testing. This study evaluates the practical and psychometric properties of the MICRA (Norwegian translation) in tested ovarian cancer patient. Methods: Since 2002, ovarian cancer patients at Oslo University Hospital, Norwegian Radium Hospital are offered genetic counseling and testing. By the end of 2009, 1,032 were included. The 530 (51%) patients still alive, were mailed the MICRA and three other instruments relevant for mental distress. 354 (67%) patients responded. Among them 9% were BRCA mutation carriers, 7% had a personal history of breast cancer, 29% had a family history of breast and/or ovarian cancer, and 55% had no such family history. Results: In the BRCA mutation carrier group, the total MICRA score and its subscale scores of distress, uncertainty, and positive experiences were all significantly higher than in the other groups. Confirmatory factor analyses of the three subscales of MICRA showed inadequate fit indices, while a four factors solution including the new factor of Support from family (items #18 and #19), showed adequate fit. The Positive Experiences subscale showed a maximum of 4% explained variance in relation to the Hospital Anxiety and Depression Scale total score, the Impact of Event Avoidance and Intrusion scores, and the Eysenck’s Neuroticism score. The subscales of Distress and Uncertainty showed maximum 12% and 41% explained variance, respectively, while the total MICRA score showed 22% explained variance. Conclusions: Our study supports the feasibility of the MICRA in ovarian cancer patients. Frail women may be identified for closer follow-up by using MICRA. Discrimant, content and construct validities of the MICRA were supported, while the factor structure still is open to further investigation.
Impact of functional outcomes on long-term quality of life after open retropubic radical prostectomy.
Authors: Loeppenberg Bjoern , von Bodman Christian , Brock Marko , Noldus Joachim , Palisaar Jueri
Published: March 2020

9580

Background: Patients who underwent open retropubic radical prostatectomy (ORRP) for prostate-cancer (PCA) have excellent long-term survival. Besides oncologic safety, recovery of continence and erectile function are highly important, as adverse functional outcomes may have a detrimental effect on health-related quality of life (HRQOL). We report the long-term HRQOL of PCA survivors after ORRP using standardized tools. Methods: Men treated between August 2003 and December 2007 with ORRP for localized PCA at a single academic hospital received validated questionnaires (International consultation on incontinence questionnaire (ICIQ), International index of erectile function (IIEF-5), Erection hardness score (EHS), EORTC QLQ-C30) to assess functional outcomes and HRQOL. Results were correlated with the global-health score (GHS) of the EORTC QLQ-C30 to assess the impact of ORRP on HRQOL. Results: In the study period 1936 men underwent ORRP of whom 1156 (59.7%) received a nerve-sparing (NS) procedure. Questionnaire return-rate was 59% (n=1141) comprising the final study cohort. Median follow-up (FU) was 62 months. Mean age at surgery and FU was 63.7±6.2 and 69.2±6.2 years, respectively. Biochemical recurrence (BCR) occurred in 17.5% (n=200/1141) and 2% (n=40/1936) deceased. Mean GHS in the study population was 71.5±20.8. In the ICIQ 28% (n=320) scored 0 indicating complete continence and 9.9% (n=113) scored ≥11 indicating severe incontinence. The corresponding GHS was 78.1±19.5 and 55.4±21.8, respectively. 68.5% (n=782) of patients used no pads and 17.9% (n=204) ≥2 pads. Corresponding GHS scores were 74.9±19.8 and 58.9±20.7. Using the IIEF-5 in men who received NS, 24.1% (n=154) had no erectile dysfunction versus 50% (n=318) using the EHS. Corresponding GHS scores were 82.2±16.3 and 74.7±19.8, respectively. Patients with BCR had a GHS of 66.8±21.8 versus 72.5±20.5 for patients without. Men who achieved the Trifecta and Pentafecta criteria had a GHS of 83.1±15.1 and 83.3±15, respectively. Conclusions: Incontinence severely impacts the HRQOL of long-term survivors after ORRP while erectile dysfunction and BCR have a lesser effect. Every effort should be undertaken to maintain functional integrity.
Utility of standardized letters in assisting primary care providers (PCPs) with the care of cancer survivors (CS).
Authors: Moghaddamjou Ali , Speers Caroline , Cheung Winson Y.
Published: March 2020

9593

Background: Survivorship care plans have strong face validity, but individualizing plans to each patient’s needs can be resource intensive. At our institution, a 1-page standardized letter that outlines the essential components of follow-up care is mailed to PCPs at the time of a patient’s discharge. This letter highlights the recommended frequency and interval of tests and physician visits. Our study aims were to 1) characterize PCPs’ attitudes regarding these letters and 2) identify potential strategies to improve this channel of communication with PCPs. Methods: Self-administered surveys were mailed to high-volume PCPs in British Columbia, defined as those whose practices followed >/=5 breast or colorectal CS in the preceding year. The survey asked about practice characteristics and PCPs’ views towards the content and format of these standardized letters. Logistic regression models were constructed to delineate factors associated with follow-up preferences. Results: Among 787 PCPs, 507 (64%) responded: median year since graduation was 27 (range 1-62), 67% were men, 38% had a faculty appointment, 71% practiced in a group, and 92% were paid fee-for-service. When asked about their perspectives regarding the care of CS, 388 (77%) indicated they were comfortable providing follow-up with 299 (74%) reporting that the standardized letter contained adequate information. In regression models, PCPs who were comfortable with cancer surveillance and those who graduated greater than 30 years ago were more likely to view the standardized letter as useful (OR 2.50, 95% CI 1.41-4.43 and OR 2.31, 95% CI 1.24-4.33, respectively) and important (OR 4.07, 95% CI 1.80-9.19 and OR 3.14, 95% CI 1.01-9.74, respectively). Among 103 (26%) PCPs who found the letter to be insufficient, most wanted additional details about the cancer diagnosis (88%), specific information on the toxicities of therapy (88%), and the estimated risk of recurrence (84%). Conclusions: Most PCPS were satisfied with a simple, standardized letter that outlines the necessary components of cancer follow-up. PCPs with less familiarity with cancer surveillance may be a target group that benefits most from individualized survivorship care plans.
Aprepitant, granisetrone, and dexamethasone for prevention of CINV after high-dose melphalan in autologous transplantation: Results of a randomized, placebo-controlled phase III trial.
Authors: Schmitt Thomas , Goldschmidt Hartmut , Neben Kai , Freiberger Anja , Huesing Johannes , Gronkowski Martina , Thalheimer Markus , Pelzl Le Hang , Mikus Gerd , Burhenne Juergen , Ho Anthony D. , Egerer Gerlinde
Published: March 2020

9612

Background: Aprepitant (A) is a NK1-antagonist approved for prevention of chemotherapy-induced nausea and vomiting (CINV). Though melphalan (M) is regarded only moderately emetogenic, CINV after high-dose M conditioning in autologous TPX can severely interfere with patients’ (pts) quality of life. Here we present the results of our monocentric, randomized (1:1), placebo-controlled, double-blind phase IIIb trial of A, granisetrone (G) and dexamethasone (D) in this setting. Methods: Pts were treated with A 125 mg po day 1, A 80 mg po days 2-4, G 2 mg po days 1-4 and D 4 mg po day 1, D 2 mg po days 2-3 (arm A) or placebo (P) days 1-4, G 2 mg po days 1-4 and D 8 mg day 1, D 4 mg days 2-3 (arm B). Melphalan 100 mg/m² iv was administered days 1-2. Episodes of emesis, modified functional living index – emesis questionnaire (FLIE) and intensity of nausea by visual analogue scale (VAS) were recorded between days 1-6. Primary endpoint was defined as no episode of vomiting and no additional antiemetic therapy within 120h of M administration. Results: Between 07/05 and 01/12 a total of 362 pts were randomized. 361 subjects (arm A=180; arm B=181; male n=229; female n=132; median age arm A=59.5 years; median age arm B=58 years) were available for the efficacy analysis. There were no significant differences in gender distribution and previous experience of CINV. Significantly less pts receiving A failed the primary endpoint (42% vs. 59%, OR=0.53 [0.34; 0.82], p=.0046). This effect was stressed in women (57% vs. 82%, OR=0.30) and patients with previous CINV (48% vs. 71%, OR=0.38). Emesis within 120h occurred in 22% of pts receiving A and 35% receiving P (OR=0.5 [0.31; 0.80], p=.0036). Though differences in overall nausea (16% vs. 22%, OR=0.65 [0.83; 1.10], p=.11) did not reach statistical significance, major nausea (VAS >25mm) was reduced (6% vs. 12%, OR=0.42 [0.19; 0.92], p=.026). Difference in FLIE score was -8.2 (p=.0007). Study medication was well tolerated. PK analyses showed no interaction between M and A. Conclusions: The combination therapy with A resulted in significantly less CINV compared to placebo. This effect was pronounced in women and pts with previous CINV. Clinical trial information: NCT00571168.
Is there an additional health-related quality of life (HRQL) benefit with abiraterone acetate (AA) in metastatic castration-resistant prostate cancer (mCRPC) beyond that mediated by clinical endpoints?
Authors: Cella David , Molina Arturo , Gagnon Dennis D. , Espindle Derek , Hao Yanni , Basch Ethan M.
Published: March 2020

9617

Background: HRQL was evaluated as part of COU-AA-301, a randomized phase 3 trial of AA + prednisone (P) vs placebo + P in mCRPC patients (pts) post-docetaxel, where AA + P demonstrated significant benefits over P in numerous HRQL measures. Here we report post hoc analyses investigating the role of disease progression (px) in mediating the HRQL benefits of AA. Methods: Intensity of pain and fatigue and their interference with daily activities were assessed with the BPI-SF and BFI questionnaires and multiple domains of HRQL with the FACT-P questionnaire. Mediation analyses were conducted using a series of 3 models (Baron & Kenny J Pers Soc Psychol 1986), to assess whether presence and timing of disease px mediated treatment effects of AA + P vs P on HRQL changes: in Model 1, HRQL (i.e. the outcome variable) is predicted by treatment, in Model 2, px (i.e. the mediator variable) is predicted by treatment, and in Model 3, HRQL is predicted by both treatment and px. Three different disease px indicators (ie, PSA px, radiographic px, and a composite px variable) were used. Results: Treatment predicted the change in FACT-P total score from baseline (Model 1; p = 0.011). Treatment (as sole predictor) was significantly (p ≤ 0.001) predictive of both PSA px and radiographic px (Model 2). Some of the treatment benefit of AA + P on the FACT-P total score was not explained as the result of the effect of treatment on PSA and radiographic px (Model 3; p = 0.030). In Model 3, pts with late (> 250 d post-randomization) or no px had better FACT-P scores than those with early px for PSA px (p = 0.019, no px; p = 0.008, late px) and radiographic px (p = 0.054, no px; p = 0.017, late px). Models evaluating the mediating role of the composite px variable showed the same pattern of results. Identical sets of mediation analyses conducted for the BPI and BFI also exhibited very similar outcomes. Conclusions: In post-docetaxel mCRPC pts, the benefits of AA to HRQL appear to be related to both treatment assignment and the mediating effects of disease px. HRQL end points expand understanding of treatment benefit beyond clinical disease px end points. Clinical trial information: NCT00638690.
N-telopeptide of type I collagen (NTX) dynamics over one year of determinations in patients with breast cancer (BC) with bone metastases (BM): Predictive factors of outcome.
Authors: Shan Ning , Alho Irina , Matias Margarida , Faria Mariana , Casimiro Sandra , Ferreira Arlindo , Leitzel Kim , Ali Suhail M. , Lipton Allan , Costa Luis
Published: March 2020

9634

Background: The bone resorption marker NTX at baseline is a prognostic marker in BC patients with BM treated with zoledronic acid (ZOL), Coleman RE, JCO 2005. We investigate how the response of urinary NTX levels during ZOL therapy is related to patient outcome and disease characteristics. Methods: Consecutive BC patients with BM were prospectively included if they received monthly intravenous ZOL. Urinary NTX was determined at baseline and at following 1, 3, 6, 9 and 12 months from the initial ZOL treatment. NTX levels were considered elevated if > 50 nmol/mmol creatinine. The NTX changes were compared with patient and disease characteristics. Relative risks for negative clinical outcomes were estimated with Cox regression models. Results: Seventy-one BC patients with BM, mean aged 61.4 (29-87), were included. Mean survival was 34.1 months (3-131), with 21 patients alive after the last follow up (median 29 months). Thirty-nine patients also had extraskeletal metastases (BM-E+). Totally 329 urinary NTX samples were evaluated. At baseline, mean NTX was 153.0 (15.4 – 700.7) and 78.9% had elevated levels. Mean baseline NTX increased with age: 71.2 (<40); 139.3 (50-59); 241.8 (70-79). Among patients with normal NTX at 3 months, 89.5% continued to show normal NTX at 12 months. After ZOL treatments, 46.9%, 54.7%, and 61.0% of patients had normal NTX at 3, 6 and 12 months, respectively. NTX variance (1-12 months) was higher for BM-E+ patients compared with BM-only patients, p<0.001. Risk factor of death for patients with persistent elevated NTX at 3 months was 1.74 (p=0.074). Age and BM-E+ were also associated with risk of death. There was a trend to shorter survival in BC-E+ patients (p=0.056). Majority of patients (88.2%) with longer survival (> 36 months) and younger (age < 60) received endocrine therapy. Conclusions: Early (3 months) urinary NTX normalization to ZOL correlates with long-term NTX normalization and survival. BC-E+ patients have a reduced NTX normalization rate compared to BM-only patients and may deserve further investigation for a more adequate schedule of bone-targeting agents.
S0221: Comparison of two schedules of paclitaxel as adjuvant therapy for breast cancer.
Authors: Budd G. Thomas , Barlow William E. , Moore Halle C. F. , Hobday Timothy J. , Stewart James A. , Isaacs Claudine , Salim Muhammad , Cho Jonathan K. , Rinn Kristine , Albain Kathy S. , Chew Helen K. , Burton Gary Von , Moore Timothy David , Srkalovic Gordan , McGregor Bradley Alexander , Flaherty Lawrence E. , Livingston Robert B. , Lew Danika , Gralow Julie , Hortobagyi Gabriel N.
Published: March 2020

CRA1008

The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Monday, June, 3, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Evaluation of TOP2A and TIMP-1 as predictive markers of pathologic complete response to neoadjuvant anthracycline-based chemotherapy.
Authors: Maia Joyce Maria L. , Santos Elizabeth Santana , Lessa Rafael Costa , Costa Felipe D'Almeida , Bezerra Stephania , Rocha Rafael Malagoli , Benevides Carlos Frederico Lopes , Lima Vladmir C. , Ribeiro Adriana Regina G. , Fanelli Marcello Ferretti , da Costa Alexandre Andre Balieiro Anastacio , Mello Celso Abdon
Published: March 2020

e11503

Background: Factors predictive of response to anthracyclines can help selecting patients who really benefit from its use. HER2 amplification, TOP2A aberrations, and changes in tissue inhibitor of metalloproteinase (TIMP-1) expression in breast carcinomas have been shown to be associated with incremental benefit from anthracycline chemotherapy. Methods: We retrospectively analyzed data on the outcome of patients undergoing neoadjuvant anthracycline-based chemotherapy. Evaluated nuclear TOP2A protein expression and cytoplasmatic TIMP-1 expression in tumor cells in breast cancer biopsies by immunohistochemistry (IHC) and reviewed the pathological responses after completion of neoadjuvant treatment. Results: From 2002 to 2012, data from 97 patients was reviewed. Sixty four patients had the paraffin blocks corresponding to the pre-treatment biopsy to analysis the TOP2A and forty nine to TIMP-1. Patients were considered positive for TOP2A if the level of expression in IHC was higher than 20% and graduated TIMP-1 as weak, moderate or strong expression. Thirty percent of the patients achieved pathologic complete response (pCR) in pos-treatment surgical specimens. There was an association between TOP2A IHC expression and tumor pathological complete response (pCR) with higher pCR in TOPO2A positive tumors (pCR 44% vs 14%; p=0.008). There was no association between TIMP-1 expression and pCR. A moderate or strong TIMP-1 expression was associated with higher disease-free survival in multivariate analysis (p=0,005). No difference in PFS and OS was observed between patients with pCR after a median follow-up of 36 months. Conclusions: The expression of TOP2A seems to be a promising predictive biomarker of pCR to antracycline-based neoadjuvant chemotherapy in HER2 breast cancer. The predictive value and form of assessment of TIMP-1 remain uncertain. These findings should be better evaluated in prospective neoadjuvant trials.