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  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 1528-1528
    Abstract: 1528 Background: The COVID-19 pandemic has disrupted US healthcare delivery and led to delays in life-prolonging therapy for some conditions. Its impact on diagnosis and timely care delivery for patients (pts) with cancer is unknown. We assessed the pandemic’s impact on time from advanced diagnosis to systemic treatment initiation (TTI) for pts with newly diagnosed advanced solid cancers. Methods: We performed a controlled interrupted time series analysis using the nationwide Flatiron Health electronic health record-derived de-identified database, which originated from ̃280 US cancer clinics. The study sample included pts ≥ 18 years diagnosed with advanced solid cancers from Jan 1-Jul 31 in 2019 or in 2020, excluding a 30-day period (Mar 8-Apr 7) encompassing the start of most state stay-at-home orders. We used Cox proportional hazards models to estimate standardized predicted probabilities of TTI within 30 days of advanced diagnosis before (Jan-Mar) and during (Apr-Jul) the pandemic in 2020, compared to historical controls in 2019, adjusted for age, sex, race, insurance, performance status, and cancer type. Interactions by cancer type and race examined heterogeneity of effects. Results: The study included 12,977 pts (median age 69 yrs [IQR 61-77]; 47.4% female; 59.4% non-Hispanic white). At the time of analysis, fewer advanced cancer diagnoses were recorded in 2020 (Jan-Mar 2,409; Apr-Jul 3,027) than in 2019 (Jan-Mar 2,910; Apr-Jul 4,631). Compared to Apr-Jul 2019, pts diagnosed with advanced cancer during the COVID-19 period were more likely to have de novo (vs recurrent) disease (67.3% vs 56.8%). In adjusted models, the COVID-19 period was associated with an increased probability of treatment within 30 days (adjusted difference-in-differences +5.2 percentage points [ppts] ). TTI improvements were not observed for pts with advanced breast cancer or Black pts, but effect differences across subgroups were not statistically significant (Table). Conclusions: Among pts diagnosed with advanced cancer, the COVID-19 pandemic was associated with shorter time to systemic therapy initiation. These treatment patterns may reflect the fewer advanced cancer diagnoses and higher proportion of de novo cancers observed during this period. Longer follow-up and data maturity are needed to understand the impact of the pandemic on clinical outcomes.[Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 2
    In: JNCI: Journal of the National Cancer Institute, Oxford University Press (OUP), Vol. 114, No. 4 ( 2022-04-11), p. 571-578
    Abstract: The COVID-19 pandemic has led to delays in patients seeking care for life-threatening conditions; however, its impact on treatment patterns for patients with metastatic cancer is unknown. We assessed the COVID-19 pandemic’s impact on time to treatment initiation (TTI) and treatment selection for patients newly diagnosed with metastatic solid cancer. Methods We used an electronic health record–derived longitudinal database curated via technology-enabled abstraction to identify 14 136 US patients newly diagnosed with de novo or recurrent metastatic solid cancer between January 1 and July 31 in 2019 or 2020. Patients received care at approximately 280 predominantly community-based oncology practices. Controlled interrupted time series analyses assessed the impact of the COVID-19 pandemic period (April-July 2020) on TTI, defined as the number of days from metastatic diagnosis to receipt of first-line systemic therapy, and use of myelosuppressive therapy. Results The adjusted probability of treatment within 30 days of diagnosis was similar across periods (January-March 2019 = 41.7%, 95% confidence interval [CI] = 32.2% to 51.1%; April-July 2019 = 42.6%, 95% CI = 32.4% to 52.7%; January-March 2020 = 44.5%, 95% CI = 30.4% to 58.6%; April-July 2020 = 46.8%, 95% CI= 34.6% to 59.0%; adjusted percentage-point difference-in-differences = 1.4%, 95% CI = −2.7% to 5.5%). Among 5962 patients who received first-line systemic therapy, there was no association between the pandemic period and use of myelosuppressive therapy (adjusted percentage-point difference-in-differences = 1.6%, 95% CI = −2.6% to 5.8%). There was no meaningful effect modification by cancer type, race, or age. Conclusions Despite known pandemic-related delays in surveillance and diagnosis, the COVID-19 pandemic did not affect TTI or treatment selection for patients with metastatic solid cancers.
    Type of Medium: Online Resource
    ISSN: 0027-8874 , 1460-2105
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    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2992-0
    detail.hit.zdb_id: 1465951-7
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  • 3
    In: Pharmacoepidemiology and Drug Safety, Wiley, Vol. 32, No. 1 ( 2023-01), p. 66-72
    Abstract: Our objective was to describe differences in telemedicine use among women with metastatic breast cancer (mBC) by race, age, and geographic region. Methods This was a retrospective cohort study of women with recurrent or de novo mBC treated in US community cancer practices that initiated a new line of therapy between March 2020 and February 2021. Multivariable modified Poisson regression models were used to calculate adjusted rate ratios (RR) and robust 95% confidence intervals (CI) associated with telemedicine visits within 90 days of therapy initiation. Results Overall, among 3412 women with mBC, 751 (22%) patients had telemedicine visits following therapy initiation, with lower risks observed among older women ( 〈 50 years: 24%; 50–64 years: 22%; 65–74 years: 21%; ≥75 years: 20%). Greater telemedicine use was observed among Asian women (35%) compared to White (21%), Black (18%), and Hispanic (21%) women. Fewer telemedicine visits occurred in Southern (12%) and Midwestern (17%) states versus Northeastern (37%) or Western (36%) states. In multivariable models, women ages ≥75 years had significantly lower risks of telemedicine visits (RR = 0.76, 95% CI 0.62–0.95) compared to ages 〈 50 years. Compared to patients in Northeastern states, women in Midwestern (RR = 0.46, 95% CI 0.37–0.57) and Southern (RR = 0.31, 95% CI 0.26–0.37) states had significantly lower risks of telemedicine visits; but not women in Western states (RR = 0.96, 95% CI 0.83–1.12). No statistically significant differences in telemedicine use were found between racial groups in overall multivariable models. Conclusions In this study of community cancer practices, older mBC patients and those living in Southern and Midwestern states were less likely to have telemedicine visits. Preferences for communication and delivery of care may have implications for measurement of exposures and endpoints in pharmacoepidemiologic studies of cancer patients.
    Type of Medium: Online Resource
    ISSN: 1053-8569 , 1099-1557
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 1491218-1
    SSG: 15,3
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  • 4
    In: JAMA Oncology, American Medical Association (AMA), Vol. 4, No. 3 ( 2018-03-08), p. e173420-
    Type of Medium: Online Resource
    ISSN: 2374-2437
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2018
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 4075-4075
    Abstract: 4075 Background: DKK1 is a secreted modulator of Wnt signaling often expressed in tumors, including BTC. DKK1 expression in BTC is associated with advanced stage and shorter survival. Depletion of DKK1 has efficacy in BTC xenograft models, inhibits cell invasion, and decreases MMP9 and VEGF-C expression, known promoters of metastasis and angiogenesis. D is a humanized monoclonal antibody against DKK1. This study evaluated the safety and efficacy of D in combination with GC in pts with advanced BTC. Methods: In Part A, pts received D at either 150 or 300 mg (and 300 mg D in Part B expansion) with 1000 mg/m2 G and 25 mg/m2 C on days 1 and 8 of each 21-day cycle. Response assessed every 2 cycles using RECISTv1.1. Results: 27 pts were enrolled; 4 dosed at 150 mg and 23 dosed at 300 mg. Median age: 65; Female: 74%; White: 85%. Gallbladder cancer 37%, intrahepatic cholangiocarcinoma 59%. 3 pts had prior G: 2 pts with adjuvant G; 1 pt with 2 prior regimens. Median number of cycles with D: 8 (range 1, 17). Median duration on study 6.8 mos; 8 pts still on therapy. No dose limiting toxicities or D-related serious adverse events have been observed. 24 pts (89%) had grade 3/4 treatment emergent adverse events (TEAEs); events in ≥ 3 pts include: neutropenia (n = 19), leukopenia (n = 9), thrombocytopenia (n = 9), hyperbilirubinemia (n = 6), anemia (n = 5), AST/ALT elevation (n = 4), and ALP elevation, bacteremia, hypertension, and hyponatremia (n = 3 each). The MTD of D + GC was 300 mg. At the MTD; 7 pts had a confirmed partial response (PR), 14 pts had stable disease 〉 6 weeks, and 1 pt had progressive disease. Both overall and MTD median PFS were 9.4 mos (95% CI 4.6, NE); median overall survival and duration of response were not reached. Conclusions: The addition of D (300 mg) to GC demonstrated a preliminary PFS of 9.4 mos and disease control rate of 96% with a 32% PR rate in pts with BTC. D + GC is well tolerated with no new emerging safety trends. Clinical trial information: NCT02375880.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 6
    In: British Journal of Cancer, Springer Science and Business Media LLC, Vol. 117, No. 12 ( 2017-12), p. 1874-1882
    Type of Medium: Online Resource
    ISSN: 0007-0920 , 1532-1827
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2002452-6
    detail.hit.zdb_id: 80075-2
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  • 7
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  Journal of Clinical Oncology Vol. 32, No. 15_suppl ( 2014-05-20), p. e15188-e15188
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 15_suppl ( 2014-05-20), p. e15188-e15188
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
    detail.hit.zdb_id: 2005181-5
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 3_suppl ( 2015-01-20), p. TPS495-TPS495
    Abstract: TPS495 Background: The activin receptor-like kinase (ALK1) pathway is a novel target in angiogenesis that promotes blood vessel maturation and stabilization. ALK1 binds to the ligand bone morphogenetic protein 9 (BMP9) which is overexpressed in hepatocellular carcinoma (HCC) compared to normal hepatocytes. Dalantercept is an ALK1 receptor fusion protein that binds BMP9 and acts as a ligand trap. Sorafenib, a multi-kinase and vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR TKI), is the standard therapy for advanced HCC. In a preclinical model of HCC, simultaneous blockade of ALK1 and VEGF signaling with dalantercept and sorafenib resulted in additive tumor growth inhibition. In a completed Phase 1 study in thirty-seven subjects with solid tumors, dalantercept monotherapy demonstrated preliminary anti-tumor activity and a safety profile that was generally non-overlapping with VEGFR TKIs. Methods: An open label, multi-center, dose escalating, phase 1b study to evaluate dalantercept plus sorafenib in subjects with advanced HCC is ongoing. The primary endpoint includes the evaluation of the safety and tolerability of dalantercept plus sorafenib and determination of the recommended phase 2 dose levels of the combination. Secondary endpoints include assessments of the pharmacokinetic profile of the combination, preliminary activity including response rate using RECIST 1.1 and time to progression, and pharmacodynamic biomarkers in the serum and tissue including ALK1 and BMP9 expression. In the first two cohorts of 3-6 subjects each, the dalantercept dose levels will be 0.6 and 0.9 mg/kg, respectively, administered subcutaneously (SC) every 3 weeks in combination with sorafenib 400 mg PO once daily. In cohort three, 3-6 subjects will receive dalantercept dose level 0.9 mg/kg SC every 3 weeks with sorafenib 400 mg PO twice daily. Patient safety data through day 22 will be evaluated prior to escalation to the next cohort. An expansion cohort will enroll 10-20 subjects at or below the maximum tolerated dose level. Key eligibility criteria: histologically confirmed advanced HCC, Child-Pugh A liver disease, ECOG performance status of 0-1, and no prior systemic therapy in the advanced setting. Clinical trial information: NCT02024087.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
    detail.hit.zdb_id: 2005181-5
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  • 9
    In: The Oncologist, Oxford University Press (OUP), Vol. 24, No. 2 ( 2019-02-01), p. 161-e70
    Abstract: Patients with hepatocellular carcinoma (HCC) often have limited therapeutic responses to the vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor sorafenib, which is standard of care in advanced HCC. Targeting the activin receptor-like kinase 1 (ALK1) and VEGF pathways simultaneously by combining the ALK1 ligand trap dalantercept with sorafenib may result in more effective angiogenic blockade and delay tumor progression in patients with advanced HCC. Although the combination was generally well tolerated, there was no additive antitumor activity with the combination of dalantercept plus sorafenib in patients with advanced HCC. No complete or partial responses were observed, and overall survival ranged from 1.9 to 23.3 months. These results suggest that, in this patient population, further development of the possible limited benefits of combination therapy with dalantercept plus sorafenib is not warranted. Background Targeting the activin receptor-like kinase 1 (ALK1) and vascular endothelial growth factor (VEGF) pathways may result in more effective angiogenic blockade in patients with hepatocellular carcinoma (HCC). Methods In this phase Ib study, patients with advanced HCC were enrolled to dose-escalation cohorts, starting at 0.6 mg/kg dalantercept subcutaneously every 3 weeks plus 400 mg sorafenib orally once daily, or to a dose expansion cohort. The primary objective was to determine the safety and tolerability and the dalantercept maximum tolerated dose (MTD) level. Secondary objectives were to assess the preliminary activity and the association of pharmacodynamic biomarkers with tumor response. Results A total of 21 patients were enrolled in the study. Five patients received 0.6 mg/kg dalantercept in the first dose escalation cohort. Based on the initial safety results, the dose level was de-escalated to 0.4 mg/kg in the second cohort (n = 6). The MTD was identified as 0.4 mg/kg and used for the dose expansion cohort (n = 10). At this dose level, the combination was generally well tolerated. Overall survival ranged from 1.9 to 23.3 months, and the best overall response was stable disease. Conclusion The addition of dalantercept to sorafenib did not improve antitumor activity in patients with HCC. The dalantercept program in this population was discontinued.
    Type of Medium: Online Resource
    ISSN: 1083-7159 , 1549-490X
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2023829-0
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  • 10
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2015
    In:  Cancer Research Vol. 75, No. 13_Supplement ( 2015-07-01), p. B29-B29
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 13_Supplement ( 2015-07-01), p. B29-B29
    Abstract: Background: Serum carbohydrate antigen (CA) 19-9 levels are often elevated in pancreatic cancer, and the degree of elevation has been used for de facto disease staging and prognostication. Previous studies and conventional wisdom suggest artificially elevated CA19-9 levels in the setting of obstructive jaundice, but the true incidence and degree of additional elevation is unknown. This study attempts to quantify the change in CA19-9 associated with relief of biliary obstruction via endoscopic stent placement in a pancreatic cancer patient population. Methods: Retrospective review of pancreatic cancer patients who underwent initial endoscopic stent placement for obstructive jaundice at a single, academic medical center from 2001 to 2011. Eligibility for this study included serum CA19-9 and total bilirubin (TB) levels within 10 days prior to and 30 days after endoscopic intervention. Patients with elevated CA19-9 and TB levels prior to endoscopy were included in analysis. Patients undergoing pancreatic surgery, chemotherapy, or radiotherapy prior to second CA19-9, or without post-stent decrease in TB, were excluded. Univariate analyses of patient and tumor characteristics by Fisher’s exact test. Patients who met above criteria were assessed by percent change in CA19-9. Results: Of 1,242 patients with pancreatic cancer, 627 underwent endoscopic procedures. In all, 16 patients had CA19-9 and TB levels both: 1) within 10 days prior to, and 2) within 30 days after initial endoscopic stent placement and a drop in TB, without interval pancreatic cancer-directed therapy. Initial CA19-9 levels varied from 82 u/mL to 48,122 u/mL with a median of 1,825 u/mL (IQR 346, 12,321). Median change in CA19-9 level was 26 u/mL (IQR -41, 7,056); percent change varied between -100% and 654% (median 11%; IQR -8%, 158%). The time between CA19-9 levels ranged from 1 to 31 days (median 13; IQR 10, 21). A single patient showed a dramatic drop in CA19-9. She experienced a 99.89% decrease in CA19-9, from 18,107 u/mL to 20 u/mL with 31 days between serum sampling. She was categorized as a remote outlier and removed from further analysis. Five patients demonstrated a drop in CA19-9, ranging from -1% to -31%. The median decrease was 120 u/mL (IQR -14, -588), and the median % decrease was 13% (IQR -7%, -15%; maximum drop 31%). Median days between CA19-9 was 11 (IQR 4, 11), with median time after stent to 2nd CA19-9 being 11 days (IQR 4, 11). Nine patients demonstrated an increase in CA19-9, ranging from 1% to 654%. The median increase was 3,250 u/mL (IQR 164, 20,297), and the median % increase was 95% (IQR 21%, 330%). Median days between CA19-9 was 16 (IQR 10, 21), with median time after stent to 2nd CA19-9 being 12 days (IQR 8, 20). Conclusions: CA19-9 is a serum biomarker used for risk prediction in pancreatic cancer among other gastrointestinal conditions. In the pancreatic cancer population, high CA19-9 levels are associated with worse long-term outcomes. In our cohort, the majority of patients did not have a decrease in CA19-9 following relief of obstruction. A subset of patients experienced large increases in CA19-9 despite effective stenting, which could represent disease progression. Based on our data, we propose a maximum 15% decrease in CA19-9 as a correction factor in the setting of obstructive jaundice to aid in pancreatic cancer prognostication. Citation Format: Lindsay A. Bliss, Douglas K. Pleskow, Mariam F. Eskander, Catherine J. Yang, Rebecca A. Miksad, Sing Chau Ng, Tyler M. Berzin, Mandeep S. Sawhney, Ram Chuttani, Jennifer F. Tseng. Adjusting CA19-9 for biliary obstruction in pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B29.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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