bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cancer patients’ trade-offs for efficacy, toxicity, and cost.
Authors: Wong Yu-Ning , Egleston Brian , Sachdeva Kush , Hamilton Olivia , Eghan Naa , Pirollo Melanie , Stump Tammy K , Beck J Robert , Meropol Neal J. 
Published: March 2020

6021 Background: When making treatment decisions, cancer patients (pts) must make trade-offs between efficacy, toxicity (tox) and cost. However, little is known about how individual characteristics influence these decisions, particularly as many face high out of pocket costs. Methods: We presented cancer pts with hypothetical scenarios that asked them to choose between 2 treatments of varying levels of efficacy, tox and cost. Each scenario included 9 choice pairs. Pts were given 2 of 3 scenarios described in the Table. Tox was also varied. Demographics, cost concerns and numeracy were assessed. Within each scenario, we used latent class methods to distinguish pt groups with discrete preferences. We then used regressions with group membership probabilities as covariates to identify associations. Results: We enrolled 400 pts. Median age was 61 years (range 27-90). 63% were female. 41% were college educated. 51% had an annual income ≥$60K. 25% were enrolled at a community hospital. 98% were insured. Within each of the 3 scenarios, we identified 3 pt classes with preferences for survival or aversion to high cost or toxicity. Across each of the scenarios, <6% of pts in the group averse to high cost chose the costlier treatment. >92% of pts in the group that favored survival chose the highest efficacy treatment. >65% of pts in the group with aversion to tox chose the lower tox treatment. Within each of the scenarios, pts in the group with preference for survival were more likely to have an income of >$60K (p<.05) and greater numeracy skills (p<.05). In scenarios 2 and 3, pts with concerns about treatment costs were more likely to be in the class that was averse to high cost (p<.05 for both). Conclusions: Even in hypothetical scenarios presented to insured pts, socioeconomic status was predictive of treatment choice. Higher income pts may be more likely to focus on survival when making decisions while those with greater cost concerns may be more likely to avoid costly treatment, regardless of survival or tox. This raises the possibility that health plans with greater cost-sharing may have the unintended consequence of increasing disparities in care. [Table: see text]
The involvement of partners in breast cancer treatment decision making.
Authors: Hawley Sarah T. , Janz Nancy K. , Lillie Sarah E , Schwartz Kendra L. , Graff John , Hamilton Ann S. , Katz Steven J. 
Published: March 2020

6023 Background: Incorporating partners into treatment decision making is an important element of patient-centered care, yet little is known about the role of partners in the decision process. Methods: We surveyed 503 partners of a population-based sample of breast cancer survivor 4 years after diagnosis (RR= 76%, N=382).The outcome was partners’ reports of decision regret. Independent variables included decision making process measures (partners’ reports of sufficient treatment information receipt and sufficient involvement in decision making), race/ethnicity, age, education and income. Multivariable logistic regression was used to assess associations between decision regret and race/ethnicity, controlling for other variables. Results: 49% of partners were white, 14% African American, 15% more-acculturated Latino, and 18% less-acculturated Latino. One quarter (26%) of partners reported that they received insufficient information and one third (35%) desired more involvement in decision-making. Compared to whites, less-acculturated Latino partners more often reported that they received insufficient information (41% vs. 18%, p<0.05) and desired more involvement in decision-making (49% vs. 14%, p<0.001). Overall 30% of partners reported high decision regret. Multivariate analyses showed factors associated with high decision regret were less-acculturated Latinos, insufficient information receipt and desire for more involvement (Table). Conclusions: Most partners of breast cancer survivors reported low decision regret and positively appraised their involvement in the decision process. Less acculturated Latinos reported more dissatisfaction with the decision process. Findings suggest the need for culturally appropriate treatment decision support interventions that include partners. [Table: see text]
Conflict of interest disclosure in off-label oncology clinical trials.
Authors: Irwin Blair Billings , Abernethy Amy Pickar , Hirsch Bradford Richard 
Published: March 2020

6041 Background: Off-label prescribing of anti-cancer targeted therapies is increasingly prevalent. Post-regulatory evidence and reporting requirements for reimbursement for off-label oncologic indications are less stringent than the threshold for United States Food and Drug Administration registration. What are the prevalence, reliability, and predictors of conflict of interest (COI) and funding disclosure statements in published reports of studies of cancer targeted therapies conducted in the post-regulatory setting? Methods: As a part of a federally-funded systematic review, manuscripts were included in the analysis if they were used to support one of 19 indications for cancer targeted therapies that were off-label but reimbursable according to authoritative compendia in 2006 or before. Studies were categorized according to trial design, trial results, average impact factor of journals, and the presence of COI and funding disclosure statements. Results: Sixty-nine studies were included in the systematic review. Prevalence of COI and funding disclosures was low, at 33% and 58%, respectively; time trends showed some improvement between 2002 to 2007, but only 60% of studies had disclosures by 2007. Predictors of COI disclosure were publication in high impact factor journals (p<0.001), large study sample size (p=0.001), enrollment exclusively in the US (p=0.04), and study of the targeted therapy in combination with other agents as opposed to the study drug alone (p=0.03). Studies with multiple sites were more likely to include a funding disclosure statement (p=0.01). Conclusions: There is need for more consistent disclosure of potential sources of bias in COI and funding statements in studies of off-label indications for anti-cancer targeted therapies.
Cost-effectiveness of biomarker-directed bevacizumab for first-line therapy of persons with metastatic colorectal cancer.
Authors: Berry Kristin , Bensink Mark Eliot , Musa Zahra , Shankaran Veena , Lin Edward H. , Ladabaum Uri , Bodnar Carolyn , Birt Michael , Ramsey Scott David 
Published: March 2020

6077 Background: When added to first-line chemotherapy for metastatic colorectal cancer, bevacizumab provides a moderate survival increase, but is associated with significant adverse events and high cost. As only a minority of patients respond to antiangiogenic therapy, a diagnostic that identifies potential responders ex ante could potentially change the benefit to risk profile of bevacizumab and likely improve cost-effectiveness. Since efforts to identify a predictive test have so far been unsuccessful, a novel strategy may be to measure tumor response after bevacizumab treatment initiation using an in vivo biomarker test to guide decisions on whether patients should continue treatment. The objective is to estimate the cost-effectiveness of biomarker-directed use of bevacizumab in first-line treatment of metastatic colorectal cancer compared to standard care. Methods: The analysis takes the perspective of the US healthcare system. A decision model was built to estimate the incremental effect of adding bevacizumab to IFL, FOLFIRI, 5FU/LV and FOLOFOX/XELOX regimens. Survival data, estimated through a meta-analysis of four clinical trials, combined with utilities from the literature were used to calculate quality-adjusted life years (QALYs). Costs were based on Medicare reimbursement and expert opinion. Assumed performance characteristics of the biomarker technology (sensitivity, specificity – provided by our industry partner) were 75% and 95% 10 days after commencement of bevacizumab. Results: The biomarker-directed bevacizumab strategy dominated usual care, providing both an average per patient gain of 0.015 QALYs and a cost-savings of $21,038. The cost-effectiveness of the biomarker technology was most influenced by the cost of the test and colorectal cancer utilities. Variations in biomarker specificity and sensitivity changed the magnitude of cost-savings and benefit gain but did not change the overall result of dominance. Conclusions: Modeling predicts that a validated marker which could identify responders to bevacizumab will save money and improve quality-adjusted life years. The results support additional investment in identifying such a diagnostic.
Quality of life of elderly patients undergoing concomitant chemoradiation therapy for head and neck cancers, including assessment of geriatric parameters.
Authors: Extermann Martine , Fulp William J , Lee Ji-Hyun , Kish Julie Ann , Sehovic Marina , Poon Donald , Gwede Clement 
Published: March 2020

6100 Background: Data on the quality of life of older patients undergoing concomitant chemoradiation therapy (CCRT) for head and neck (H&N) cancer are very scarce and no study has focused specifically on them. Furthermore, no study has assessed the contribution of geriatric symptoms to their quality of life. Methods: We prospectively assessed patients aged 65 and older undergoing curative intent CCRT for H&N cancers, either alone or adjuvantly after surgery. We used the Quality of life-Radiation Therapy Instrument (QOL-RTI), with its H&N module (Trotti et al., 1998). In addition we created a 12-items senior adult questionnaire (SAQ). Patients were assessed at baseline, at 4 weeks, at the end of treatment (EOT), and 2 months after EOT (recovery). Results: Fifty patients were enrolled. Median age was 69 years (range 65-87). Eighty-two percent of patients had locally advanced stage IV disease. Twenty-eight percent had prior surgery. All patients were treated with IMRT, 92% at 70 Gy. The most frequent chemotherapy regimen was cisplatin q3wks (58%), followed by weekly carboplatin (24%). Patients had on average 4 comorbidities (CIRS-G), 54% of them a grade 3 or 4 disease. Forty-four percent were independent in IADL, and 98% were ECOG PS 0 or 1. The baseline scores were QOL-RTI: 7.72 (SD 1.36), H&N module 7.7 (SD 2.16), SAQ 8.21 (SD 1.54). At EOT, the scores were 6.22 (1.26), 4.59 (1.82), 7.38 (1.38) respectively, and at recovery 7.17 (1.25), 6.06 (1.66), 7.96 (1.16). The scores paralleled functional evolution, as 24% of patients had an ECOG PS 2 and 76% were IADL dependent at EOT; 16% ECOG 2-3 and 55% IADL dependent at recovery. Cronbach alphas for the 3 QOL measures were 0.88, 0.89, and 0.81, suggesting adequate internal consistency reliability. The SAQ was low-to-moderately correlated with the other two QOL measures (r=0.22 to 0.59) at different points of assessment. Conclusions: Older H&N cancer patients experience significant impact of CCRT on their function, and on their quality of life on all three measures. Most recover after two months, although some may take longer. A geriatric module adds significant information to the general QOL-RTI and H&N questionnaires.
A phase I dose-escalation study evaluating weekly paclitaxel with neratinib and trastuzumab in women with metastatic HER2-positive breast cancer, NSABP FB-8.
Authors: Jankowitz Rachel Catherine , Abraham Jame , Tan Antoinette R. , Limentani Steven A. , Adamson Laura M , Buyse Marc E. , Jacobs Samuel A. , Wolmark Norman 
Published: March 2020

611 Background: Dual blockade of ErbB receptors combined with chemotherapy compared with single-agent blockade improves efficacy in HER2-positive disease. FB-8 is single arm, Phase I dose-escalation study to determine safety and tolerability of weekly paclitaxel (P), the irreversible tyrosine kinase inhibitor, neratinib (N) and trastuzumab (T) in women with metastatic, HER2-positive breast cancer (MBC). Methods: Women with measurable or non-measurable MBC (ECOG PS 0 - 2) received P (80 mg/m2 IV days 1, 8, 15 of 28-day cycle), T (4 mg/kg IV, then 2 mg/kg IV weekly), and N (oral, daily). N was dose-escalated using 3+3 design at 120 mg, 160 mg, and 240 mg, dose-limiting toxicity (DLT) determined in cycle 1. All patients (pts) received prophylactic anti-diarrheals. Results: All pts were taxane and trastuzumab pre-treated, with mean of 4 prior regimens. At N=120 mg, there was 1 DLT, grade (gr) 3 diarrhea with dehydration. Three more pts were enrolled; none experienced DLT. At N=160 mg, there were no DLTs. At N=240 mg, 2 of 3 pts had DLTs: one gr 3 diarrhea and dehydration, one gr 3 diarrhea, dehydration, and gr 3 mucositis. After de-escalation to N=160 mg, 3 more pts were added. If N=160 mg is well tolerated, a 200 mg cohort is planned. 12 pts completed cycle 1. Efficacy data are available on 10: CR 1, PR 3, SD 1 (8+months). One pt* had resolution of non-target disease (skin and breast mass). 4 pts were off-study before the first scan (DLT 3 and progressive disease 1) and are considered non-responders (NR). The most frequent grade 3-4 adverse event was diarrhea, 3 pts. Conclusions: Dual anti-HER blockade with N, T combined with P is tolerable and highly active in pts pre-treated with anti-HER2 agents and chemotherapy. This combination will be studied in a phase II neoadjuvant breast cancer trial (NSABP FB-7). We thank Pfizer, Inc and Puma Biotechnology, Inc for their support. [Table: see text]
Financial relationships with commercial interests (COI) among abstracts at the ASCO Annual Meeting.
Authors: Bradbury Angela R. , Moy Beverly , Peppercorn Jeffrey M. , Egleston Brian , Sands Colleen B. , Sheikh-Salah Moktar , Storm Courtney D. , Helft Paul R. 
Published: March 2020

6128 Background: ASCO has a formal policy that requires disclosure of COI with entities having a commercial interest in research. There are limited data describing the frequency and type of COI reported in cancer research and how these have changed over time. Methods: We reviewed author-reported COI for abstracts submitted for the ASCO Annual Meeting in 2006 and 2008–2011. COI are classified as employment, stock, consultant, honoraria, research, expert witness, and other. Logistic regression models were used to evaluate the association between COI and acceptance at the annual meeting and change over time. Results: 37% of all abstracts reported at least one author with a COI. Any COI increased significantly from 33% in 2006 to 39% in 2011 (p<0.001). Any COI and all categories of COI were significantly more prevalent among abstracts accepted for presentation compared to those accepted for publication only (Table). Among abstracts accepted for presentation, any COI increased from 39% in 2006 to 48% in 2011 (p<0.001) Increases by year were statistically significant for overall (p<0.001), honoraria (p=0.045), and research (p=0.002) COI. Conclusions: Many authors submitting abstracts accepted for presentation at the ASCO Annual Meeting disclose COI. Reported COI have increased over time and are significantly more frequent among abstracts accepted for presentation than for publication only. These data suggest either that cancer research increasingly involves relationships with industry or that COI reporting has become more common. Policies to manage and foster these relationships will continue to be required and revised. [Table: see text]
Inotuzumab ozogamycin (I0), a CD22 monoclonal antibody conjugated to calecheamicin, given weekly, for refractory-relapse acute lymphocytic leukemia (R-R ALL).
Authors: Jabbour Elias , O'Brien Susan Mary , Thomas Deborah A. , Jorgensen Jeffrey L. , Kebriaei Partow , Rytting Michael E. , York Sergernne , Ravandi Farhad , Kwari Monica , Faderl Stefan , Rios Mary Beth , Cortes Jorge E. , Fayad Luis , Tarnai Robert , Wang Sa , Champlin Richard E. , Advani Anjali S. , Kantarjian Hagop 
Published: March 2020

6501 Background: Patients (pts) with R-R ALL have a poor prognosis. CD22 is highly expressed in ALL. We have previously reported on 49 pts with R-R ALL treated with IO at the dose of 1.8 mg/m2 every 3-4 weeks; the overall response rate was 57%. From preclinical studies, lower dose more frequent exposure schedules to IO may offer better anti-ALL activity. Methods: Pts with R-R ALL received IO 0.8 mg/m2 on Day 1, 0.5 mg/m2 on Day 8, and 0.5 mg/m2 on Day 15. The total dose per course remained the same 1.8 mg/m2. Courses were given every 3-4 weeks. Early stopping rules were implemented for an overall response rate < 40%. Results: 20 pts were treated so far. Median age was 57 yrs (range 22–84). Cytogenetics were: Ph+ in 7 (35%), t(4:11) in 2 (10%) , diploid in 3 (15%), and other in 8 (40%). CD22 was expressed in > 50% blasts in all pts and in > 90% in 14 (70%). Median number of courses so far was 2 (1–4). 9 (45%) pts received IO as salvage 1 (S1), 5 (25%) as salvage 2 (S2), 6 (30%) as salvage 3 (S3). one pt had allo SCT before IO. Median follow-up is 22 weeks (range, 7-43). Overall, 2/20 pts (10%) achieved CR, 6 had CRp (30%), 2 had marrow CR (10%), 8 were resistant, 2 died within 4 wks. Overall, CR+CRp+mCR (OR) was 50%: S1 6/9 (67%); S2 2/5 (40%); S3 2/6 (33%). Of the 10 responders, 7 pts (70%) became MRD negative. There were no clear correlations between OR and pts/ALL characteristics or with CD22 expression vs. < 90%. In 16 pts with evaluable pharmacokinetics studies, the median end of the infusion levels of IO were 117 ng/ml and 77 ng/ml in responders and non-responders, respectively. Median survival was 7+ months. Median OR duration was 5+ months. Median survival in 10 responders has not been reached. Liver function abnormalities (LFA) were noted as IO related in 7 (35%) pts, severe and reversible in 2 (10%). 4 pts were able to proceed to allo SCT (1 in CR, 3 in CRp) after a median of 4 weeks from the last infusion of IO; No cases of veno-occlusive disease were observed. Conclusions: IO given weekly is active in R-R ALL with an OR of 50%. LFAs occur and are reversible. This study of IO weekly schedule is ongoing. IO and chemotherapy combinations are being pursued.
PACE: A pivotal phase II trial of ponatinib in patients with CML and Ph+ALL resistant or intolerant to dasatinib or nilotinib, or with the T315I mutation.
Authors: Cortes Jorge E. , Kim Dong-Wook , Pinilla-Ibarz Javier , Paquette Ronald , le Coutre Philipp D. , Chuah Charles , Nicolini Franck E. , Apperley Jane , Khoury Hanna Jean , Talpaz Moshe , DiPersio John F , DeAngelo Daniel J , Rea Delphine , Abruzzese Elisabetta , Müller Martin C , Baccarani Michele , Gambacorti-Passerini Carlo , Turner Christopher D. , Haluska Frank G. , Kantarjian Hagop 
Published: March 2020

6503 Background: Ponatinib is a potent, oral, pan-BCR-ABL inhibitor active against the native enzyme and all tested resistant mutants, including the uniformly resistant T315I mutation. Methods: The PACE (Ponatinib Ph+ALL and CML Evaluation) trial started Sept 2010. Pts with refractory CML (CP, AP or BP) or Ph+ALL resistant or intolerant (R/I) to dasatinib or nilotinib or with T315I received 45 mg ponatinib once daily. The trial is ongoing; enrollment completed Sept 2011. Data as of 17 Jan 2012 are reported. Results: 449 pts were enrolled, 5 of whom were ineligible (post-imatinib, non-T315I) but treated. Median age was 59 (18-94) yrs; 53% male. Diagnoses were: 271 CP-CML (R/I=207; T315I=64); 79 AP-CML (R/I=60; T315I=19); 94 BP/ALL (R/I=48; T315I=46). Median time from diagnosis to ponatinib was 6 yrs. Prior TKIs included imatinib (96%), dasatinib (85%), nilotinib (66%), bosutinib (7%); 94% failed ≥2 prior TKIs, 59% failed ≥3 prior TKIs. 83% had a history of resistance to dasatinib or nilotinib; 12% were purely intolerant. In CP, best response to most recent dasatinib or nilotinib was MCyR 25%. Frequent mutations confirmed at entry: 29% T315I, 8% F317L, 4% E255K, 4 % F359V, 3% G250E. Median follow-up was 6.6 months. Response rates are presented in the table. Overall, 64% remained on therapy (77% CP). Most frequent reasons for discontinuation were progression (12%) and AE (10%). Most common drug‑related AEs were thrombocytopenia (33%), rash (33%), dry skin (26%). Conclusions: Ponatinib has substantial activity in heavily pretreated pts and those with refractory T315I. Response rates continue to improve with longer follow-up. Multivariate analyses of predictors of outcome will be presented. [Table: see text]
Subcutaneous omacetaxine mepesuccinate in patients with chronic phase (CP) or accelerated phase (AP) chronic myeloid leukemia (CML) resistant/intolerant to two or three approved tyrosine-kinase inhibitors (TKIs).
Authors: Nicolini Franck E. , Lipton Jeffrey Howard , Kantarjian Hagop , Wetzler Meir , Akard Luke Paul , Baccarani Michele , Craig Adam , Nanda Nisha , Brown Peter D. , Cortes Jorge E. 
Published: March 2020

6513 Background: Omacetaxine mepesuccinate (“omacetaxine”) is a first-in-class, reversible, transient inhibitor of protein elongation that facilitates tumor cell death without depending on BCR-ABL signaling. Clinical activity was shown in two phase 2, open-label, multicenter studies in treatment-resistant CML. Methods: A subset from the phase 2 studies included patients in CP or AP who were resistant/intolerant to ≥2 approved TKIs. Omacetaxine 1.25 mg/m2 was given SC twice daily: ≤14 consecutive days/28-day cycle for induction, ≤7 days/cycle as maintenance. Secondary results were calculated for responses by number of prior TKIs. Results: Of 122 patients (median age, 60 years), 62 had received 2 TKIs (100% imatinib; 76% dasatinib; 24% nilotinib) and 60 had received all 3 approved TKIs. Prior non-TKI therapies (eg, 52% hydroxyurea, 34% interferon) were common. Of 45 CP patients in the 2 TKI group, 12 (27%) had major cytogenetic response (MCyR; median duration of 17.7 mo), and of 36 in the 3 TKI group, 4 (11%) had MCyR (median duration not reached). Of 17 AP patients in the 2 TKI group, 6 (35%) had major hematologic response (MaHR; median duration, 13.4 mo), and of 24 in the 3 TKI group, 5 (21%) had MaHR (median duration, 6.4 mo). Median months of survival in the 2 and 3 TKI groups were 30.1 and not reached for CP and 12.0 and 24.6 for AP. Treatment-related grade 3/4 adverse events (AEs) occurred in 52 (84%) patients in the 2 TKI group and 42 (70%) in the 3 TKI group (most common: thrombocytopenia [71%, 48%]). Fifteen (24%) and 16 (27%) had an AE leading to discontinuation, primarily disease progression. There were 20 deaths (primarily disease progression), 11 in the 2 TKI group and 9 in the 3 TKI group; 4 were considered related to treatment (sepsis in 2, pancytopenia, febrile neutropenia). Conclusions: In patients with heavily pretreated CML, response to omacetaxine therapy occurred whether they had received 2 or 3 prior TKIs. The drug was well tolerated. Tolerability was similar across the TKI groups in both CP and AP patients. Support: Teva Pharmaceutical Industries Ltd.