tbuckley/cabot-search huggingface dataset:
Abemaciclib with or without fulvestrant for the treatment of hormone receptor-positive and HER2-negative metastatic breast cancer with disease progression following prior treatment with palbociclib.
Authors: Keerthi Tamragouri, Melody A. Cobleigh, Ruta D. Rao
Journal: Journal of Clinical Oncology (2019)

e12533 Background: Abemaciclib is a selective inhibitor of CDK4 and CDK6 kinase activity. It is approved for patients with hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative, advanced or metastatic breast cancer (MBC) previously treated: in combination with fulvestrant for patients with disease progression following endocrine therapy (MONARCH 2) and as monotherapy for patients with disease progression after endocrine therapy and chemotherapy for MBC (MONARCH 1). The patients in these trials were CDK 4/6 inhibitor-naïve. It has not yet been studied in patients who previously received a CDK 4/6 inhibitor. Methods: We performed a chart review of patients with HR positive, HER2-negative MBC treated at Rush University Medical Center who progressed on palbociclib, either with an aromatase inhibitor (AI) or fulvestrant, and were subsequently treated with abemaciclib with or without fulvestrant. We documented patient demographics, prior treatment, and response to abemaciclib therapy. Results: 21 female patients, mean age 57.8 (+/- 13.2y), were included. Patients had received 1-5 prior lines of endocrine therapy and 0 – 4 prior lines of chemotherapy for MBC. All patients received prior palbociclib: 14 patients with an AI, 6 patients with fulvestrant, and 1 patient received palbociclib with an AI and then with fulvestrant. Of the 21 patients, 17 were treated with abemaciclib monotherapy and 4 received abemaciclib with fulvestrant. SD was seen in 19% of patients (4/21) and 62% had PD (13/21). The CBR was 29% (6/21) and all of these patients received abemaciclib monotherapy. Due to expected toxicities of the drug (diarrhea, neutropenia, and thrombocytopenia), 19% (4/21) of patients discontinued treatment. 4 patients continued abemaciclib monotherapy for greater than 8.3M. 3 patients were on treatment for less than 35 days; 2 stopped due to expected toxicities and one had progression of disease on physical exam. Median treatment duration was 3.1M. Conclusions: This retrospective chart review of 21 patients demonstrates that abemaciclib has limited activity as a single agent in patients previously treated with palbociclib.
Economic burden associated with cervical cancer: An analysis of patient-reported outcomes in the United States.
Authors: Chizoba Nwankwo, Nate Alexander Way, Vicky Weitian Li
Journal: Journal of Clinical Oncology (2019)

e17021 Background: Although much is known about the prevention, screening, and treatment of cervical cancer (CC), less is known about its economic burden. This study compared patient-reported outcomes (PROs) between women diagnosed and treated for CC, women diagnosed and untreated for CC, and women without CC. Methods: Data were aggregated from the 2013-2015 US National Health and Wellness Surveys, a nationally-representative, self-administered, internet-based survey of adults (N = 269,447). Controlling for baseline patient demographics and characteristics, three matched cohorts were compared in multivariable analysis: treated CC, untreated CC, and no CC. Treated CC and untreated CC patients with other forms of comorbid cancer were excluded from analyses. Economic outcomes included healthcare resource use (HCRU) over the past six months and annualized direct costs. Direct costs were calculated using Medical Expenditure Panel Survey data. Results: Adjusted means are reported. Treated CC (N = 192), untreated CC (N = 829), and no CC (N = 1,018) cohorts largely differed by number of healthcare provider (HCP) visits (0.95 vs. 0.89 vs. 0.84, p’s &lt; 0.05), hospitalizations (0.18 vs. 0.09 vs. 0.10, p’s &lt; 0.05), and ER visits (0.29 vs. 0.19 vs. 0.16, p’s &lt; 0.05), though the difference between untreated CC and no CC cohorts was not significant for hospitalizations nor ER visits. Treated CC, untreated CC, and no CC cohorts also largely differed by HCP costs ($14,143 vs. $11,187 vs. $10,573, p’s &lt; 0.01), hospitalization costs ($12,006 vs. $4,202 vs. $4,908, p’s &lt; 0.01), ER costs ($2,104 vs. $995 vs. $872, p’s &lt; 0.01), and total direct costs ($30,768 vs. $16,613 vs. $16,776, p’s &lt; 0.01), though the difference between untreated CC and no CC cohorts was not significant for HCP costs nor total direct costs. Conclusions: These results indicate substantial economic burden in women diagnosed with CC in the US. In terms of HCRU and direct costs, treated CC patients incur the greatest burden, untreated CC patients incur the second greatest burden, and individuals without CC tend to incur the least burden.
Chemotherapy in KRAS-mutated chemotherapy naive non-small cell lung cancer patients: A phase III comparing cisplatin-pemetrexed with carboplatin-paclitaxel-bevacizumab: NVALT 22 (NCT02743923).
Authors: Anne-Marie C. Dingemans, Egbert F. Smit, Joop De Langen, Harm van Tinteren
Journal: Journal of Clinical Oncology (2019)

TPS9127 Background: In a retrospective analysis of KRAS mutated non-small cell lung cancer (NSCLC) patients response and progression free survival (PFS) to first line chemotherapy was better for carboplatin-paclitaxel-bevacizumab then other first line combinations (Mellema Lung Cancer, 2015:90:249-54). Methods: Trial Design: Multi-center open label randomized phase III study. After stratification for KRAS mutation (G12V versus G12C versus other), performance status (0-1 vs. 2) and brain metastasis (yes of no) patients will be 1:1 randomized to carboplatin-paclitaxel-bevacizumab or cisplatin-pemetrexed q3wks for up to six cycles. Continuation maintenance with bevacizumab and pemetrexed is allowed until progression. Study population: histologically or cytologically confirmed stage IIIB or stage IV KRAS mutated NSCLC patients who are eligible for platinum-based chemotherapy and are chemotherapy naïve. Previous anti-PD(L1) therapy for advanced disease is allowed (amendment 25.1.2018). Response will be assessed according to RECIST 1.1, CT scans will be made every 6 weeks until progression. Blood and archival tissue will be optionally collected for translational research. This may help to identify subgroups of patients who are likely better treated with a specific treatment regimen. Statistical analysis: The trial was designed to demonstrate superiority of the carboplatin-paclitaxel-bevacizumab treatment over cisplatin-pemetrexed with an assumed hazard ratio of 0.67. In total 201 events are required for the final analysis, corresponding to a total sample size of 240 patients to be accrued. There is a single interim analysis planned after 101 events have been observed. Primary endpoint: PFS defined by the response criteria in solid tumors (RECIST) and assessed by independent review. Secondary endpoints: Overall response rate, Overall Survival, outcome according to type of KRAS mutation, response assessed by CRABB criteria. Study progress: Currently 25 sites are open across the Netherlands and 170 of the 240 required patients are randomized (February 12, 2019). Clinical trial information: NCT02743923.
Risk of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) in a cohort of 3,546 women prospectively followed after receiving textured breast implants.
Authors: Paola Ghione, Peter G. Cordeiro, Ai Ni, Qunying Hu, Nivetha Ganesan, Natasha Galasso, Ahmet Dogan, Steven M. Horwitz
Journal: Journal of Clinical Oncology (2019)

1565 Background: Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a rare subtype of T-cell lymphoma, developing in in the fluid or capsule surrounding breast implants, primarily or exclusively in those with textured surfaces. Several prior series have estimated the risk of BIA- ALCL at 1/6920 - 1/3800 women in retrospectively defined cohorts (from diagnosed cases within national or pathology databases), approximating the population at risk from sales records or other estimates (Sirinvasa 2017; Loch-Wilkinson 2017; de Boer 2018). Methods: A prospective cohort study was conducted in the population that underwent breast reconstruction by a single surgeon at Memorial Sloan Kettering Cancer Center (MSKCC) from April 1993 to December 2017. Patients had long-term follow-up, and events related to implants were prospectively recorded. We identified all cases of BIA-ALCL by cross-checking data from internal clinical records, pathology records, and outside reports. Incidence rate per person-years and cumulative incidence when accounting for competing risk were calculated. 134 women who received smooth-surface implants were excluded from the analysis, since these implants have not been associated with BIA-ALCL. Results: From 1993 to 2017, 3546 patients underwent 6023 breast reconstructions using textured surface implants. All reconstructions were performed by a single surgeon (PGC) on patients enrolled in this study. To identify BIA-ALCL occurrence, clinical and pathological data were assessed from a prospective database. Median follow-up was 7 years (range, 3 days - 24.7 years). Eight women developed ALCL after a median exposure of 11.2 years (range, 8.3-15.8 years). Overall risk of BIA-ALCL in this cohort was 0.294 cases per 1000 person-years (1/443 women). Conclusions: This study, evaluating the risk of women with textured breast implants from a prospective database with long-term follow-up, demonstrated that the incidence rate of BIA-ALCL may be higher than previously reported. These results can help inform implant choice for women undergoing breast reconstruction.
Economic analysis of alternative pembrolizumab and nivolumab dosing strategies at an academic cancer center.
Authors: Evan Thomas Hall, Jenny Zhang, Eun-Jeong Kim, Grace Hwang, Shailender Bhatia, Sunil A. Reddy
Journal: Journal of Clinical Oncology (2019)

6504 Background: Pembrolizumab (P) and nivolumab (N) were initially investigated and FDA-approved with weight-based dosing strategies, but later the approval label was amended to a fixed dose administration. Given increasing concerns about financial toxicity of cancer therapies, we hypothesize that weight-based dosing of P and N and allowing vial sharing among patients will result in substantial cost savings. Methods: We obtained IRB approval to retrospectively examine all outpatient doses of P and N given at three Stanford Medicine infusion centers between July 1, 2018 and Oct 31, 2018 using the Stanford Medicine Research Data Repository (STARR) database. We performed cost-minimization analysis modeling the impact of dosing strategies based upon patient weight versus fixed dosing (2 mg/kg vs 200 mg q3wks for P; 3 mg/kg vs 240 mg q2wks or 6 mg/kg vs 480 q4wks for N). “Dose-minimization” (DM) was defined as whichever dose was lower (weight-based or fixed dose). The impact of allowing vial sharing (considering commercially available vial sizes) between patients treated at the same site and on the same date was assessed. Average sales price (ASP) from Center for Medicare and Medicaid Services for Part B drugs was used for cost estimates. Results: A total of 1,029 doses of P or N were administered across a variety of cancer types. For most doses (N = 789, 77%), the calculated weight-based dose was less than the fixed dose. DM resulted in decreased usage and expenditures of both P and N, and a further decrease was observed with vial sharing. Total savings estimated with DM and vial sharing strategy were &gt; $1.4 million (Table). This amounted to savings of &gt; 22,000 mg of P (112 fixed doses) and &gt; 11000 mg of N (47 fixed doses). Savings were greatest at the highest volume infusion center. Conclusions: Alternative dosing strategies of P and N would result in significantly less drug utilization and pharmaceutical expenditure without anticipated impact on efficacy. Potential barriers to this approach include existing policies regarding vial sharing and drug vial sizes. [Table: see text]
Abstract 16542: Sex Differences in Progression of Tricuspid Regurgitation: Results From a Large-Scale Echocardiographic Study
Authors: Edgard A Prihadi, Pieter van der Bijl, Erhan Gursoy, Rachid Abou, E M Vollema, Nina Ajmone Marsan, Victoria Delgado, Jeroen J Bax
Journal: Circulation (2017)

Introduction: Large epidemiological studies and surgical registries have shown a female predominance in patients with significant tricuspid regurgitation (TR). As this sex difference has not been o...
No-cost next generation sequencing of advanced cancer patients within the Strata Precision Oncology Network supports clinical trial enrollment.
Authors: Marc Ryan Matrana, Scott A. Tomlins, Kat Kwiatkowski, Khalis Mitchell, Jennifer Marie Suga, Elizabeth Claire Dees, Mark E. Burkard, Jamil Khatri, Malek M. Safa, Eddy Shih-Hsin Yang, Benjamin Parsons, Alex R. Menter, Michael A. Thompson, Anneliese O. Gonzalez, Timothy Robert Wassenaar, Dan Rhodes
Journal: Journal of Clinical Oncology (2019)

3073 Background: Widespread integration of systematized next generation sequencing (NGS)-based precision oncology is hindered by numerous barriers. Hence, we developed the Strata trial (NCT03061305), a screening protocol to determine the impact of scaled precision oncology. Methods: We implemented no-cost NGS on formalin fixed paraffin embedded (FFPE) clinical samples for all patients with advanced tumors, a common portfolio of partnered therapeutic clinical trials, and robust infrastructure development across the Strata Precision Oncology Network. Results: Across the network of 17 centers, specimens from 8673/9222 (94%) patients were successfully tested in the Strata CLIA/CAP/NCI-MATCH accredited laboratory using comprehensive amplicon-based DNA and RNA NGS. Patients were tested with one of three StrataNGS test versions; the most recent panel assesses all classes of actionable alterations (mutations, copy number alterations, gene fusions, microsatellite instability, tumor mutation burden and PD-L1 expression). Median surface area of received FFPE tumor samples was 25mm 2 (interquartile range 9-95mm 2 ), and the median turnaround time from sample receipt to report was 6 business days. 2577 (27.9%) patients had highly actionable alterations, defined as alterations associated with within-cancer type FDA approved or NCCN guideline recommended therapies (1072 patients), NCI-MATCH trial arms (1467 patients), Strata-partnered therapeutic trials (327 patients), or specific alteration-matched FDA approved therapies in patients with cancers of unknown primary (71 patients). Of the 1467 patients matched to an NCI-MATCH trial arm, 15 enrolled. Of the 327 patients matched to one of nine Strata-partnered clinical trials, 77 (24%) were screen failures, while 250 (76%) have either enrolled or are being actively followed for enrollment upon progression. Conclusions: Through streamlined consent methods, electronic medical record queries, and high throughput laboratory testing at no cost to patients, we demonstrate that scaled precision oncology is feasible across a diverse network of healthcare systems when paired with access to relevant clinical trials. Clinical trial information: NCT03061305.
Influence of competing risks on estimates of recurrence risk and breast cancer-specific mortality in analyses of the Early Breast Cancer Trialists Collaborative Group.
Authors: Ramy Saleh, Michelle Nadler, Alexandra Desnoyers, Danielle Lee Rodin, Husam Abdel-Qadir, Eitan Amir
Journal: Journal of Clinical Oncology (2019)

533 Background: Early stage breast cancer is a curable disease with the majority of patients dying of causes other than breast cancer. The influence of these competing risks of death on the interpretation of Kaplan-Meier(KM)-based analyses such as those performed by the Early Breast Cancer Trialists Collaborative Group (EBCTCG) are unknown. Methods: We searched the Clinical Trial Service Unit and Epidemiological Studies Unit website at Oxford University to identify all meta-analyses published by the EBCTCG between 2005 and 2018. Studies were included if they contained KM curves with risk estimates for either breast cancer mortality and/or breast cancer recurrence. The potential influence of competing risks was estimated using a validated multivariate linear model that predicts the amount that the KM risk estimates are biased relative to outcome risk measured with the cumulative incidence function (CIF). Results: The initial search identified 14 analyses published by the EBCTCG with 10 of the 14 studies (71%) susceptible to competing risk bias cited both the number of events of interest and competing events. Eight of the ten studies (80%) had a relative difference between the KM estimate and the competing risk adjusted estimate of more than 10% while 2 of 10 (20%) had a difference of less than 10%. The relative difference between the KM and adjusted estimates was 28.4% for local recurrence, 16.8% for distant recurrence, and 6.7% for breast cancer-specific mortality. There was 2.2% difference between KM and adjusted analyses between 0-4 years and 18.9% beyond 10 years of follow up. Use of KM and CIF-based analysis did not influence treatment effect in the majority of included studies. Conclusions: This study provides estimates for the overestimation of risk in Kaplan-Meier analyses resulting from failure to address competing risk bias. CIFs are more appropriate to measure outcome risk over time and should be used especially for long-term follow-up studies and for analysis of rare events.
NICE guidance on depression: 35 health organisations demand “full and proper” revision
Authors: Jacqui Wise
Journal: BMJ (2019)

A coalition of health bodies has met with the National Institute for Health and Care Excellence (NICE) to call for a “full and proper revision” of its 2009 guideline on adult depression.1 The update was due to be released in January 2018 but has been delayed after extensive criticism.

The coalition, led by the Society for Psychotherapy Research, said that it still has serious concerns about significant flaws in methodology, a lack of transparency, and inconsistencies found in the updated draft guideline published in July 2017.

A position statement signed by 35 health organisations—including the All-Party Parliamentary Group for Prescribed Drug Dependence, the British Psychological Society, the British Acupuncture Council, and the South London and Maudsley NHS Foundation Trust—said that the guideline was not fit for purpose and, …
Integrin β5 in plasma-derived exosomal protein predicting liver-specific metastasis in advanced gastric cancer patients.
Authors: Qian Li, Xiaojing Xu, Yiyi Yu, Wei Li, Li Liang, Jia Song, Bin Li, Fu-Gen Li, Shangli Cai, Tianshu Liu
Journal: Journal of Clinical Oncology (2019)

e14521 Background: Gastric cancer (GC) is the second leading cause of cancer death in China. Liver metastasis (LM) is a highly frequent event of the advanced GC, and the patients with LM always present dismal prognosis. A predicted factor of LM is urgently established to screen out the population in high risk of LM. Tumor-derived exosomes play critical roles in cancer metastasis process. Exosomes integrin (ITG) αvβ5 is uptake by liver resident cells and linked to LM in cell lines. This study is designed to evaluate the association between exosomes ITG αvβ5 and liver metastasis, especially in HER2 positive gastric cancer. Methods: 74 untreated advanced GC patients with matched blood and tumor tissue samples and clinical features were collected in the study. Exosomal HER2, ITG αv and β5 expression were measured by enzyme-linked immunosorbent assay (ELISA) after the exosomes isolated from plasma. HER2 status of tumor tissue was determined by IHC and/or FISH. Results: Based on HER2 status of tumor tissue, we initially proved the feasibility of detecting HER2 expression from exosome. ROC curves showed the optimum exosomal HER2 expression diagnostic cutoff for HER2 positive patients was 266.38 pg/ml (sensitivity 71.4% and specificity 72.6%). In total, 27 patients were LM and the rest (n = 47) was non-LM. The median expression value of ITG αv and β5 were 57.55 pg/ml and 836.00 pg/ml, respectively. And these two median value were identified as the cutoff value for subsequent analysis, respectively. HER2 expression was merely linked to ITG β5 expression (P = 0.019), not ITG αv (P &gt; 0.050). There was no relationship between ITG αv and LM (P = 0.629), however, ITG β5 expression presented significant association with LM (P = 0.016). We further probed the relationship between ITG and other metastasis. Results showed no correlation between any ITG and other non-liver organic metastases, like lung, bone, ovarian, lymph, and peritoneal metastasis. Besides, ITG β5 expression was also associated with LM in the HER2-positive GC patients. Conclusions: Exosomes might serve as a potential non-invasive diagnostic and screening tool. In clinical samples, ITG β5, not αv, was linked to LM, and might be a valuable biomarker in the use of predicting LM of GC, even in the HER2-positive patients.
TCGA data reveal a transcriptomic signature of Sox2 and Nanog targets associated with survival in head and neck cancer.
Authors: Nikol Mladkova, Dukagjin Blakaj
Journal: Journal of Clinical Oncology (2019)

e17546 Background: Head and neck cancers represent a diverse group of tumors linked with HPV infection, alcohol and smoking that contribute to cancer morbidity and mortality globally. Sox2 and Nanog are transcription factors that maintain pluripotency in embryonic stem cells, and their individual expression has been associated with prognosis in head and neck tumors previously. Methods: TCGA dataset containing 522 tumor samples with RNAseq data, clinical information (anatomically classified as 133 oral tongue, 117 laryngeal, 73 oral cavity, 63 floor of mouth, 45 tonsillar, 27 base of tongue and 70 other samples) and 44 normal samples with RNAseq data available was used to detect differentially expressed genes in head and neck tumors. The levels of each gene were then transformed to z-score per patient and classified as over- or under-expressed if those were 2 SD away from the mean. The expression levels were then correlated with survival in individual patients for all tumor combined. Subgroup analysis of oral tongue, laryngeal, oral cavity, floor of mouth, tonsillar cancers was carried out separately. Results: A total of 233 genes were significantly correlated with survival in head and neck tumors ( &lt; 0.01). This geneset was subsequently analyzed for enrichment of common pathway dysregulation or for enrichment of shared regulatory elements. The expression level of a set of a total of 15 genes that represent targets of Nanog and Sox2 was shown to either increase or decrease survival directly dependent on either up- or down-regulated expression levels. Of note, neither Nanog nor Sox2 expression levels individually impacted survival. Subgroup analysis revealed individualized prognostic signatures in each anatomic location, with an overlap of individual genes with Nanog and Sox2 targets signature ranging from 6.25-20%. Conclusions: We describe a prognostic signature in head and neck tumors derived from a TCGA data consisting of genes that represent targets of critical stem cell regulators Sox2 and Nanog. On a subgroup analysis, we also derived prognostic signatures for five anatomic locations and head&amp;neck tumors with various ranges of overlap with Sox2 and Nanog targets signature. Pending validation in additional datasets, those represent an attractive target for further mechanistic evaluation in tumorigenesis in this group of tumors.