tbuckley/cabot-search huggingface dataset:
Chemotherapy in the management of olfactory neuroblastoma/esthesioneuroblastoma: An analysis of the surveillance, epidemiology, and end results (SEER) 1973-2015 database.
Authors: Lee D. Cranmer, Bonny Chau
Journal: Journal of Clinical Oncology (2019)

e17573 Background: Olfactory neuroblastoma (ON) is a malignant tumor of nasal cavity arising in sensory neuroectodermal olfactory cells. Chemotherapy (CT) has been proposed as an adjunct to primary local therapy. Here, we investigated the role of CT in primary ON treatment. Methods: SEER was searched for ON (ICD-3 9522). Inclusion criteria were (1) unique cases; (2) primary nasal cavity tumor; (3) staging information; and (4) ability to derive Kadish stage. Abstracted covariates included sex, age, tumor grade, nodal status, year of diagnosis, derived Kadish stage, and treatment (surgery, radiotherapy (RT), CT). Outcomes included disease-specific (DSS) and overall (OS) survival. In SEER, CT and RT are classified as Yes vs No/Unknown. Uni- and multi-variable Cox analyses assessed CT treatment on DSS and OS, controlling for covariates noted above. To account for proportional hazards violations, such variables were either stratified or time-varying. Multiple imputation addressed missing data. A p &lt; 0.05 was designated for statistical significance. Analyses were conducted using Stata ver 12. Results: 797 ON cases were included. In univariable analysis, CT treatment (yes vs no/unknown) was associated with inferior DSS (HR 2.81, 95% CI 2.11 3.74, p &lt; 0.001) and OS (HR 2.03, 95% CI 1.63 2.54, p &lt; 0.001). In multivariable analyses, CT was again associated with inferior DSS (HR 1.74, 95% CI 1.21, 2.51, p = 0.003) and OS (HR 1.71, 95% CI 1.26, 2.32, p = 0.001). Limiting analysis to those with local/regional disease treated with local therapy (surgery and/or radiation), CT remained associated with inferior outcomes [DSS (HR 2.78, 95% CI 1.63, 4.74, p &lt; 0.001) and OS (HR 2.17, 95% CI 1.45, 3.27, p &lt; 0.001)]. Sensitivity analyses ruled out chemotherapy misclassification as an explanation for our results. Conclusions: Our analysis does not support the use of chemotherapy to improve either DSS or OS in primary ON treatment. We controlled for known ON prognostic factors available from SEER. Other prognostic and treatment selection factors could exist for which we did not control. Chemotherapy may also beneficially affect outcomes other than DSS or OS. While concerns have been expressed regarding CT treatment misclassification in SEER, our analyses did not identify such misclassification as an explanation.
ECOG-ACRIN 5508: Pemetrexed, bevacizumab or the combination as maintenance therapy for advanced non-squamous NSCLC.
Authors: Suresh S. Ramalingam, Suzanne Eleanor Dahlberg, Chandra Prakash Belani, Joel N. Saltzman, Gopakumar S. Nambudiri, John McCann, Jerome D. Winegarden, Mohammed Azher Kassem, Mohamed K. Mohamed, Jan M. Rothman, Alan P. Lyss, Leora Horn, Tom Stinchcombe, Joan H. Schiller
Journal: Journal of Clinical Oncology (2019)

9002 Background: Maintenance therapy is a standard approach for advanced non-squamous NSCLC. Pemetrexed or bevacizumab are considered evidence-based options. The combination of bevacizumab and pemetrexed has been documented to improve progression-free survival (PFS). We conducted a phase 3 study to determine the optimal maintenance therapy for advanced NSCLC. Methods: Patients (pts) with advanced non-squamous NSCLC, no prior systemic therapy, and ECOG performance status 0/1 were treated with carboplatin (AUC = 6), paclitaxel (200 mg/m 2 ) and bevacizumab (15 mg/Kg) every 3 weeks for up to 4 cycles (step 1). Patients with CR/PR/SD after 4 cycles were then randomized 1:1:1 to maintenance therapy with bevacizumab (15 mg/Kg), pemetrexed (500 mg/m 2 ) or the combination of the two agents every 3 weeks until disease progression (step 2). The primary endpoint was overall survival (OS), defined as the time from randomization to death from any cause and censoring defined at the last date of followup. 1495 pts provided 81% power to detect a hazard ratio of 0.75 while controlling the 2-sided type I error at 0.025 for each comparison, assuming approximately 60% of those patients would be randomized. Results: We enrolled 1516 pts to step 1 (male 52%; ECOG PS 1 62%; adenocarcinoma 90%); After induction therapy, 874 (57%) pts were randomized to step 2 (median age 64 yrs; male 49%; ECOG PS 1 55%). Baseline characteristics were balanced across all three groups. The median follow-up in maintenance is 50.6 months. Conclusions: Single agent bevacizumab or pemetrexed is the optimal maintenance therapy for advanced non-squamous NSCLC. The combination of bevacizumab and pemetrexed cannot be recommended due to the lack of survival benefit in this definitive study. (Drs. Ramalingam, Dahlberg and Belani contributed equally to this work). Supported by the NCI: CA180820, CA180794,CA180799, CA180821, CA180838, CA180844, CA180847, CA180853, CA180857, CA180864, CA180867, CA180868, CA180870, CA180882, CA189830, CA189859, CA189863, CA189971. Clinical trial information: NCT01107626. [Table: see text]
A phase II trial of nintedanib in recurrent malignant pleural mesothelioma (MPM).
Authors: Antoinette J. Wozniak, Bryan J. Schneider, Gregory Peter Kalemkerian, Robert Michael Daly, Wei Chen, Jaclyn Ventimiglia, Misako Nagasaka, Marjorie Glass Zauderer
Journal: Journal of Clinical Oncology (2019)

e20061 Background: Malignant pleural mesothelioma (MPM) is a disease that is resistant to chemotherapy and there remains an unmet need for better therapeutic options. Nintedanib (BIBF 1120) is an oral multikinase inhibitor impacting VEGFR, FGFR, PDGFR, and other kinase activity such as TGFß signaling pathways. VEGF, FGF, and TGFβ are commonly expressed in MPM. We conducted a phase II trial in patients with recurrent MPM after platinum-based chemotherapy. Methods: Patients (pts) with MPM previously treated with platinum-based chemotherapy, performance status (PS) 0-1, adequate organ function, and no contraindications to anti-angiogenic therapy were eligible for treatment. Nintedanib 200 mg twice per day was administered until disease progression or unacceptable toxicity. The primary endpoint was the 4-month progression-free survival (PFS). A two-stage design was used and &gt; 4 pts had to have a PFS of ≥4 months to proceed to the second stage. Results: Twenty pts. were enrolled. The median age was 70 yrs. (32-81), 90% were male, and 80% were PS = 1. The histology was 70% epithelioidal, 5% sarcomatoid, 10% biphasic, and 15% unknown. 15% had prior bevacizumab. The median follow-up is 16.4 mo. A median of 2 treatment cycles (range 1-18) were delivered. There were no responses but 40% had stable disease. The median PFS was 1.8 mo. (95% CI: 1.68, 3.55) and the PFS rate at 4 mo. was 13%. The median OS was 4.2 mo. (95% CI: 2.53, 8.74) and the OS rate at 4 mo. was 55%. Toxicities were usually grade 1-2 and included diarrhea, fatigue, edema, transaminase elevation, anorexia, nausea, vomiting and dyspnea. Conclusions: The activity of nintedanib in previously treated MPM pts. was modest. The trial did not meet the primary PFS endpoint. However, there was a small subset of pts. that had prolonged stable disease for &gt; 4 months thus potentially deriving some clinical benefit from treatment. Supported by Boehringer Ingelheim. Clinical trial information: NCT02568449.
A comparative analysis of survival in patients with non-small cell lung cancer with brain metastases receiving intracranial radiation with and without immunotherapy.
Authors: Sunita Patruni, Ahmed Khattab, Stephen Abel, Shaakir Hasan, Saleha Rizwan, Gene Grant Finley, Dulabh K. Monga, Vivek Verma, Rodney E Wegner
Journal: Journal of Clinical Oncology (2019)

9025 Background: Many patients diagnosed with advanced non-small cell lung cancer (NSCLC) will develop intracranial metastasis, contributing significantly to morbidity and mortality. Immunotherapy (IMT) has emerged as the standard of care in select cases of metastatic NSCLC, though data investigating the survival impact of IMT and radiation (XRT) in these patients is limited. To characterize the survival impact of intracranial XRT and IMT in NSCLC patients with brain metastasis, we analyzed the National Cancer Database (NCDB). Methods: We queried the NCDB for patients with metastatic NSCLC having brain metastasis receiving intracranial XRT ± IMT. Univariable and multivariable analyses identified characteristics predictive of overall survival. Cox proportional hazard ratios with propensity matching mitigated indication bias between the two arms. Results: 13,998 NSCLC patients who received IMT (n = 545) or did not receive IMT (n = 13,545) were eligible for analysis. Univariable analysis demonstrated a median overall survival of 13.1 months (95% CI: 11.8-15.0) vs. 9.7 months (95% CI: 9.5-9.9) (p &lt; 0.0001) and 3-year overall survival of 17% vs. 12% [p &lt; 0.0001; HR: 0.77 (0.71-0.84)] in patients receiving and not receiving IMT respectively. Patients with N3 disease and those diagnosed between 2012 and 2014 were more likely to have received IMT. Receipt of IMT remained an independent predictor of increased survival on propensity score matched multivariable comparison (p = 0.0002). Conclusions: Receipt of IMT was an independent predictor of increased overall survival in patients with NSCLC having intracranial metastasis. Randomized, prospective studies are needed to further validate these findings. [Table: see text]
Apatinib combined with Raltitrexed in patients with metastatic colorectal cancer after failure of standard therapy (AHEAD-311): A single-arm phrase II pilot trial.
Authors: Haiyan Si, Miaomiao Gou, Yong Zhang, Huan Yan, Niansong Qian, Zhikuan Wang, Yan Shi, Guanghai Dai
Journal: Journal of Clinical Oncology (2019)

e15008 Background: To assess the safety and efficacy of apatinib, an oral vascular endothelial growth factor receptor-2 inhibitor, combined with thymidylate synthase inhibitor raltitrexed in patients with metastatic colorectal cancer (mCRC) as a third- or later-line therapy. Methods: Patients with mCRC after at least 2 lines of chemotherapy were enrolled whenever they previously treated with bevacizumab or not. Apatinib was given orally at 250mg or 500mg daily. Raltitrexed was administered intravenously at 3 mg/m2 on day 1 every 3 weeks. The primary endpoints were progression-free survival (PFS). The second endpoints were objective response rate (ORR), overall survival (OS) and safety. Results: From August 2017 to November 2018, thirty-one patients were enrolled in Chinese PLA General Hospital. After a median follow-up of 6.4 months, the median treatment cycle was 4. four patient achieved partial response(PR), and 11 patients achieved stable disease (SD) and 16 achieved progression disease (PD) in accordance with RECIST version 1.0, illustrating a DCR of 48.4% and an ORR of 12.9% .The Median PFS was 2.4 months and the median OS was 6.4 months. The most common adverse events were hypertension (n=12, 38.7%), nausea and vomiting (n=11, 33.8%), myelosuppression (n=9, 29.0%). The most common grade 3 to 4 adverse events were hypertension (n=2, 6.4%) and hand-foot syndrome (n=2, 6.4%). Grade 3 to 4 hematologic toxicities were rare. One patient died from cardiac arrest after three days treatment. There was no significantly association between PFS or OS, and clinical features including tumor location, KRAS status, and prior surgery or not, and number of metastatic organs. There was no trend showing patients who experienced had hypertension or myelosuppression had longer PFS and OS. Compared to the patients never received bevacizumab, the patients who had previously bevacizumab had the similar PFS and OS (3.9 versus 2.3months, P=0.787; 6.1 versus 6.4months, P=0.287). Grade1-2 nausea and vomiting and age &lt;57 were independent predictors for longer PFS and OS. Conclusions: Apatinib combined with raltitrexed had efficacy but had limited survival benefit in mCRC refractory to standard chemotherapy. This regime showed us a higher risk of adverse event incidence and warrant further exploring of benefit population. Clinical trial information: NCT03344614 .
Exceptional responders to abexinostat (ABX) plus pazopanib (PAZ) in pretreated renal cell carcinoma (RCC) and other solid tumors: Long-term follow-up of a phase 1b study.
Authors: Rahul Raj Aggarwal, Scott Thomas, Nela Pawlowska, Jennifer A. Grabowsky, Susan Calabrese, Phu Lam, Kathleen Comerford, Daphne Bautista, Pamela N. Munster
Journal: Journal of Clinical Oncology (2019)

3022 Background: We previously reported the initial phase 1b study results of PAZ + ABX, a potent pan-HDAC inhibitor, demonstrating acceptable toxicity profile and encouraging anti-tumor activity (Aggarwal et al. JCO 2017). We report the long-term follow up of exceptional responders and additional correlative analyses associated with clinical outcomes. Methods: Key efficacy endpoints included objective response rate and duration of response. Peripheral blood histone acetylation, HDAC expression, and plasma VEGF levels were analyzed and associated with clinical outcomes. Results: 51 pts (RCC subset; N = 22) were enrolled between June 2012 and October 2015. 10 pts (20%) had experienced disease progression on prior PAZ; 59% had received any prior VEGF-targeting therapy. 9 evaluable pts (18%) (N = 6 RCC; 2 thyroid; 1 mesothelioma) achieved partial tumor response (PR), of which 6 had prior progression on VEGF-targeting therapy. 7/10 (70%) of pts with prior disease progression on PAZ monotherapy had reduction in tumor burden on study. The median duration of response was 9.1 months (range 1.2 to 70+), and clinical benefit rate (PR or stable disease &gt; 6 months) was 33%. Five treatment-refractory pts achieved durable PRs lasting for &gt; 2 years duration, and one previously PAZ-refractory patient with RCC remains on treatment with ongoing PR for &gt; 6 years. Higher HDAC2 expression was associated with prolonged progression-free survival (median PFS 5.9 vs. 3.5 months, log-rank p = 0.02). Induction of histone acetylation on ABX lead-in treatment was associated with subsequent time to progression (p = 0.002). On-treatment plasma VEGF levels were inversely correlated with PBMC histone acetylation (p = 0.02). Conclusions: Markedly durable responses with PAZ + ABX are achievable, including in pts with PAZ- and VEGF-refractory RCC and other solid tumor malignancies. Host factors including HDAC expression and acetylation status may identify those most likely to benefit. A randomized phase 3 study is underway of PAZ + ABX as a first- or second-line therapy in pts with locally advanced or metastatic RCC (RENAVIV; NCT03592472). Clinical trial information: NCT01543763.
cfDNA analysis to reveal association of genomic features with chemotherapy response and survival in patients with pulmonary large-cell neuroendocrine carcinoma.
Authors: Minglei Zhuo, Yan-Fang Guan, Xue Yang, Lingzhi Hong, Yuqi Wang, Zhongwu Li, Runzhe Chen, Hussein Abbas, Jia Zhong, Hanxiao Chen, Zhi Dong, Xiang Zhu, Jianjie Li, Emily Roarty, Waree Rinsurongkawong, Jeff Lewis, Andrew Futreal, Xuefeng Xia, Jianjun Zhang, Jun Zhao
Journal: Journal of Clinical Oncology (2019)

e14555 Background: The optimal systemic treatment for pulmonary large-cell neuroendocrine carcinoma (LCNEC) is still under debate. Previous studies showed that LCNEC with different genomic characteristics might respond differently to different chemotherapy regimens suggesting the potential role of genomic profiling in therapeutic decision-making. Tumor biopsies are often inadequate for genomic profiling, while cell-free DNA (cfDNA) analysis has demonstrated great potential in genomic profiling. Methods: A total of 63 patients with LCNEC treated with different chemotherapy regimens (etoposide-platinum doublets, pemetrexed with platinum and gemcitabine, docetaxel, or paclitaxel with platinum, hereafter referred to as SCLC-PE, NSCLC-PEM and NSCLC-GEM/TAX) were enrolled in this study. Samples were collected and included tumor DNA only from 22 patients, cfDNA only from 18 patients and paired tumor DNA and plasma cfDNA from 23 patients. Tumor DNA and cfDNA were sequenced by target-captured 179 genes from Geneplus-Beijing or Oncomine Cancer Panel v3 or 70 genes panel from Guardant 360. Survival and response analyses were only applied to 54 patients who received first line chemotherapy. Results: The mutation landscape of frequently mutated cancer genes in LCNEC from cfDNA closely resembled that from tumor DNA, which led to a 90% concordance in genomic subtyping. We classified LCNEC harboring any of these alterations: RB1 mutation/loss, PTEN mutation/loss, FGFR1/FGFR4 mutation/amplification, TP53 loss, as “SCLC-like” tumors, otherwise as NSCLC-like. Overall, patients with SCLC-like LCNEC had a shorter overall survival (OS) than those with NSCLC-like LCNEC (10.3 vs 14.4 months, p = 0.32) despite higher response rate (RR) (41% vs 22%) to chemotherapy. Furthermore, treatment with SCLC-PE was associated with longer PFS in SCLC-like LCNEC compared to NSCLC-PEM and NSCLC-GEM/TAX (median 8.3 vs 2.3 months, p = 0.0002; median 8.3 vs 5.9 months, p = 0.05), while treatment with NSCLC-GEM/TAX led to a shorter survival compared to SCLC-PE (median 1.9 vs 4.1 months, p = 0.03) or NSCLC-PEM in NSCLC-like LCNEC patients (median 1.9 vs 4 months, p = 0.07). Conclusions: Genomic subtyping has potentials in prognostication and therapeutic decision-making for patients with LCNEC and cfDNA analysis is a reliable alternative for genomic profiling of LCNEC.
Cognitive effects of androgen receptor (AR) directed therapies for advanced cancer of the prostate (COGCaP).
Authors: Julie Van, David F. Penson, Alfred Rademaker, James C. Jackson, Kelvin A. Moses, Alicia K. Morgans
Journal: Journal of Clinical Oncology (2019)

TPS5098 Background: Androgen deprivation therapy (ADT) is the cornerstone of treatment for prostate cancer (CaP). However, the relationship between ADT and the development of cognitive dysfunction in men with CaP is controversial. Past studies had various methodological limitations, including the inconsistency and insensitivity of measures used for cognitive testing. Methods: COGCaP is a multi-site, prospective observational study of cognitive function and patient reported outcomes in men with CaP treated with ADT and androgen receptor (AR) directed therapies such as enzalutamide or abiraterone acetate (AA) conducted across four U.S. sites. Patients with metastatic castration-resistant or hormone sensitive CaP starting abiraterone (N=50), or non-metastatic or metastatic castration-resistant CaP starting enzalutamide (N=50) undergo cognitive and patient reported outcome assessments at baseline, 3, 6, and 12 months. The primary endpoint compares mean change in cognitive function between groups at 3 months using CANTAB, a computer-based measure of cognitive function. This design achieves a power of 80% to detect a between-group difference in mean cognitive composite score of &lt; 1 standard deviation and a two-sided type I error rate of 0.05. Functional MRI (fMRI) images will be assessed between baseline and 3 months to assess structural and functional changes in the brain as secondary endpoints. Study patients will be incorporated into a model of genetic risk of cognitive dysfunction in order to identify populations that are especially vulnerable to cognitive change when undergoing androgen deprivation. This ongoing study will define a reproducible methodology for cognitive assessments via computer based tests that can be standardized and disseminated within multi-site trials of men with CaP. Clinical trial information: NCT03016741.
Phase III non-randomized controlled trial of PROMPT-Care, an eHealth intervention utilizing patient reported outcomes in routine clinical care: Impact on emergency department presentations.
Authors: Afaf Girgis, Ivana Durcinoska, Anthony Arnold, Nasreen Kaadan, Andrew Alexis Miller, Joseph Descallar, Geoff Delaney
Journal: Journal of Clinical Oncology (2019)

6510 Background: The significant impact of routine assessment and clinical utilization of patient-reported outcomes (PRO) on patient and survival outcomes and reduced emergency department (ED) presentations has been demonstrated in specific patient populations (e.g. advanced cancer). This controlled trial evaluated the impact of an eHealth system, PROMPT-Care, on ED presentations in a diverse population of cancer patients from four oncology treatments centers. Methods: All adult patients receiving cancer care (including adjuvant therapy and follow-up) were eligible, excepting those with a diagnosis of a hematological malignancy, insufficient English literacy or no internet access outside of the clinic. Intervention (PROMPT-Care) patients completed monthly online assessments comprising 61 items of distress, common symptoms and unmet needs, with PRO results electronically transferred into the electronic medical record (EMR). In “real-time”, the care team accessed patients’ PRO summary reports to guide their care, an email alert notified nurses of ongoing unresolved issues between visits, and patients received links to support self-management. Control group patients (n = 2,288) comprised the general cancer patient population receiving usual care at the participating cancer therapy centers. Multivariable negative binomial regression was used to compare between-group differences. Results: From April 2016 to March 2018, 345 eligible patients (mean age 62, 58% female, 27% stage IV) participated and were sent at least four assessments within the first six months on trial. On average, control patients had 30 ED presentations and PROMPT-Care patients had 21 ED presentations per 10,000 patient days. After adjusting for age, sex and stage of disease, PROMPT-Care patients had 26% (95% CI 0.2%, 57%) fewer ED presentations compared to the control group (p = 0.0483). Conclusions: The PROMPT-Care intervention resulted in significantly fewer ED presentations in a broad population of cancer patients, including those currently undergoing cancer treatment or are in follow-up, and patients with a wide range of tumor types. The results support its utility as an improved model for ongoing supportive care for a diverse population, with potential healthcare cost savings. Clinical trial information: ACTRN12616000615482.