tbuckley/cabot-search huggingface dataset:
Target versus non-target lesions in determining disease progression: Analysis of 581 patients.
Authors: Stephen Raskin, Eyal Klang, Tehila Kharizman, Eli Konen, Raanan Berger, Michal Amitai
Journal: Journal of Clinical Oncology (2019)

e18053 Background: RECIST, among methodologies designed to provide an objective assessment of tumor response to therapy, is based on the measurement of Target Lesions (TLs) and classification of response according to an objective scale of beneficial response or progressive disease (PD). The “PD point” (the time-point at which RECIST 1.1 first classifies the trial as PD) is a common end-point in clinical trials and is defined as that point when the objective response rate is &gt; 20%. However, RECIST also allows for the subjective assessment of non-TL lesions (NTLs) and new lesions (NLs) to determine the PD point. We sought to determine which of these parameters was most influential in determining PD. Methods: We evaluated the formal RECIST 1.1 assessments for consecutive patient enrollments in randomized clinical trials prepared by two senior radiologists at our institution from 2013 through 2018. Data was evaluated at the “PD point.” Results: There were 1260 patients, with 4499 CT or MRI scans. Of these, 581 trials concluded with PD. There were seven groups (+/-/-, -/+/-, -/-/+ . . . +/+/+) according to the status of TLs, NTLs, and NLs at the PD point. In 538 patients (92.6%), TLs were unnecessary in determining the PD point. Two-thirds of these had objective response rates of &lt; 40%. Measurable and non-measurable NTLs were equally responsible for PD, and the strongest determinant of PD was the unequivocal appearance of new lesions. Conclusions: In this study, subjective parameters, as defined by RECIST 1.1, were far more likely to result in a determination of PD than objective ones. These findings may have relevance for considering the value of RECIST 1.1 as a scientific standard for therapeutic efficacy as well as in the design of new methodologies for the assessment of tumor response.
Fixed dose, dose-dense capecitabine in metastatic breast cancer.
Authors: Anne O'Dea, Meshaal Khan, Haley Isabela Haines, Bruce F. Kimler, Lauren Elizabeth Nye, Priyanka Sharma, Qamar J. Khan
Journal: Journal of Clinical Oncology (2019)

e12593 Background: Capecitabine (C) is the only oral chemotherapy agent for metastatic breast cancer (MBC), and compared to IV agents, can be continued indefinitely if toxicities can be managed. The optimal dose and schedule of C are not known. FDA approved dose of 2500 mg/m2 daily is associated with median PFS (progression free survival) of 4-5 months and dose reduction and discontinuation rates from toxicity of 35% and 16% respectively. According to Norton-Simon mathematical model of tumor growth in which dosing schedules are determined based on efficacy, a 7 day on and 7 days off (7-7) schedule of C was predicted as optimal. We report efficacy and toxicity of fixed dose C (1500 mg BID) on a 7-7 schedule in MBC. Methods: Retrospective chart review of patients with MBC treated at our institution between June 2013 and December 2018 and received fixed dose C (1500 mg BID) on a 7-7 dosing schedule were included. Results: 39 patients with MBC were identified; 14 (35%) had de novo MBC and 25 (62.5%) had recurrent disease. 31 (77.5%) had ER+ disease, 6 (15%) were HER2+, and8 (20.5%) had triple negative breast cancer (TNBC). 10 (25%) had received no prior chemotherapy, 15 (37.5%) had received 1 line of chemotherapy, and 14 (35%) had received ≥2 lines of chemotherapy. Median PFS was 13 months. PFS was 17 months in ER+ patients and 8 months in patients with TNBC. Palmar plantar erythrodysesthesia (PPE) was the most frequent toxicity with 11 (27.5%) having mild PPE, 2 (5%) with moderate PPE, and 5 (12.5%) with severe PPE. Mild diarrhea was experienced by 14 (35%) and one patient experienced severe diarrhea. One patient experienced grade 3 neutropenia. No patients discontinued C due to toxicity. 11 (27.5%) required a dose reduction. Conclusions: Fixed dose capecitabine (1500 mg oral BID) on a 7 day on and 7 day off schedule is associated with encouraging PFS and has limited toxicity and a low rate of dose reduction and therapy discontinuation. Randomized trial comparing this dose and schedule of capecitabine to standard dose and schedule of capecitabine is ongoing.
Randomized clinical trial of transcatheter arterial chemoembolization plus radiofrequency ablation versus transcatheter arterial chemoembolization for hepatocellular carcinoma with intermediate stage (BCLC stage B) hepatocellular carcinoma beyond Milan criteria.
Authors: Xin Yin, Bei Tang, Yu-Hong Gan, Yan-hong Wang, Yi Chen, Ning-lin Ge, Rongxin Chen, Lan Zhang, Boheng Zhang, Zhenggang Ren
Journal: Journal of Clinical Oncology (2019)

4077 Background: To determine treatment efficacy and safety of transarterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) (hereafter, TACE+RFA) in patients with intermediate stage (BCLC stage B) hepatocellular carcinoma (HCC) beyond Milan criteria. Methods: In this randomized clinical trial, 110 patients with intermediate stage HCC beyond Milan criteria (single tumor with diameter 5-7cm, median; 3-5 multiple nodules with diameter less than 5cm) were included and randomly assigned to TACE+RFA group (n=55) and TACE group (n=55) at liver cancer institute, Zhongshan hospital. The primary endpoint was overall survival (OS). The secondary end point was progression-free survival (PFS) , time to progress (TTP) and best objective response (BOR). Results: The median OS in TACE+RFA and TACE group were 29 and 18 months, respectively. The median TTP and BOR were 15.7 months and 69.1 % in TACE+RFA group and 12.4 months and 40.0 % in TACE group (P=0.004). The 1-, 3-, and 4-year overall survivals for TACE+RFA group and TACE group were 97.2%, 67.9% and 59.4% versus 84.0%, 46.7% and 37.3% , respectively (P = 0.008). The corresponding PFS were 47.3%, 27.2% and 21.7% versus 35.6%,15.3% and 11.4% , respectively (P = 0.04).The incidences of major complications in TACE+RFA group were comparable to those in TACE group (P=0.14). Conclusions: TACE+RFA was superior to TACE in improving tumor response and overall survival for patients with intermediate stage (BCLC stage B) hepatocellular carcinoma beyond Milan criteria. Clinical trial information: NCT03636620.
Tucatinib, palbociclib, and letrozole in HR+/HER2+ metastatic breast cancer: Report of phase IB safety cohort.
Authors: Elena Shagisultanova, Pavani Chalasani, Ursa Abigail Brown-Glaberman, William John Gradishar, Andrew Jacob Brenner, Alison Stopeck, Dexiang Gao, Tessa McSpadden, Peter Kabos, Virginia F. Borges
Journal: Journal of Clinical Oncology (2019)

1029 Background: Based on preclinical synergy, we are conducting a phase IB/II clinical trial of tucatinib (HER2 small molecule inhibitor, T), palbociclib (CDK4/6 inhibitor, P) and letrozole (aromatase inhibitor, L) in HR+/HER2+ metastatic breast cancer (MBC). Methods: Post-menopausal, or pre-menopausal women on ovarian suppression, with prior ≥2 HER2 inhibitors at any time of disease; ≥1 HER2 inhibitor for MBC or front line bone/soft tissue only disease are eligible provided ≤2 endocrine agents for MBC. Prior CDK4/6 or HER2 small molecule inhibitors are not allowed. Treatment entails T 300 mg BID, P 125 mg/day 21 days on, 7 days off, and L 2.5 mg/day. Safety was assessed using CTCAE v.4.03 with standard definitions for dose limiting toxicity (DLT). Dose reductions of T and / or P for DLTs, and discontinuation of either P or L for toxicity were allowed at any time during the study. Safety thresholds were set as DLTs in ≤7/20 pts for T, ≤15/20 pts for P, or ≤14/20 pts attributable to both T and P. Results: Phase Ib enrolled 20 pts from 11/16/17 to 12/5/18. The median age is 53y (22-70y), median number of prior lines of MBC therapy is 2 (0-5). 70% of pts have visceral disease and 45% CNS disease. Prior treatment includes 100% of pts with trastuzumab and pertuzumab, and 45% of pts with prior TDM-1. One pt required dose reduction of T; 9 (45%) had dose reduction and 2 (10%) discontinued P for DLTs. One pt discontinued L. Safety boundaries were not crossed. The most common grade (G) ≥3 toxicities were neutropenia (G3 55%, G4 15%), diarrhea (G3 20%), infections (G3 20%), thrombocytopenia (G3 10%) and mucositis (G3 10%). The frequency and type of toxicities were consistent with those previously reported for each single agent. PK analysis showed no interaction between P and T. As of 1/4/19, 14 pts (70%) remain on study (5 pts for ≥6 months) and 6 pts removed for progression. No withdrawals for toxicity and no deaths on study. The longest time on study (ongoing) is 10 months for pts without CNS disease, and 6 months for pts with CNS disease. Conclusions: T, P, L combination showed an acceptable safety profile and encouraging antitumor activity. RP2D of T is 300mg PO BID in combination with full doses of P and L. Enrollment in phase II cohort is ongoing. Clinical trial information: NCT03054363.
Phase I study of vemurafenib (VEM) and cobimetinib (COB) with heat shock protein 90 (HSP90) inhibitor XL888 in advanced BRAFV600 mutant melanoma.
Authors: Zeynep Eroglu, Ann Chen, Jiannong Li, Joseph Markowitz, Andrew Scott Brohl, Leticia Tetteh, Adam Karpisek, Hayley Taylor, Jane Messina, Vernon K. Sondak, Nikhil I. Khushalani, Keiran Smalley
Journal: Journal of Clinical Oncology (2019)

9553 Background: Resistance to BRAF+MEK inhibitors(i) in BRAF-mutant melanoma is common. Multiple resistance mechanisms involve HSP90 clients, and a phase 1 study of VEM with XL888 showed PFS rates similar to the combination of BRAF+MEKi (Eroglu, CCR, 2018). Methods: Combination of VEM (960 mg PO BID) and COB (60 mg QD for 21 of 28 days) with escalating dose cohorts of XL888 (30, 45, 60 or 90 mg PO twice weekly) was investigated in a phase 1 study of advanced melanoma, with a modified Ji dose escalation design. Dose-limiting toxicity (DLT) was defined as related grade ≥3 adverse event or inability to deliver 75% of XL888 in first 4 weeks. Results: 25 pts (9 female, median age 62, 15 with M1C disease, 6 with prior anti-PD-1 therapy) were enrolled. After 2 DLTs (rash and acute kidney injury) in first cohort, a lower dose of VEM 720 mg BID and COB 40 mg, with the same XL888 cohorts was investigated. 3 DLTs (rash) in 12 pts were observed in the XL888 60 mg cohort, which was determined as the maximum tolerated dose. Most common grade 3 toxicities included diarrhea (8), hypertension (6), rash (5), alkaline phosphate/GGT elevation (4). 11 patients required dose reductions of VEM and/or COB. Objective responses (PR/CR) were observed in 18 of 25 pts (72%; 95% CI: 51-88%). Median PFS was 8.1 months (4.7 – NA); median overall survival was not reached, with 1-year OS of 71% (45-86%). Single cell RNA-Seq (10X genomics) was performed on baseline and on-treatment tumor biopsies; 8 days of treatment was associated with an increase in immune cell influx (CD4+ and CD8+) and a decrease in number of melanoma cells. At day 8, one patient (now without progression for nearly 2 years) had no tumor cells remaining with only immune cells and stromal fibroblasts left. Further analyses will be presented. Serial plasma BRAF circulating tumor (ct)DNA levels were obtained, with decrease in ctDNA levels corresponding with response and 83% of patients with disease progression showing an elevation in ctDNA from baseline. Conclusions: VEM/COB plus XL888 had significant toxicity, requiring dose-reductions that may have contributed to the low PFS rate despite high response rate. Caution must be used in combination of BRAF+MEKi with other agents. Clinical trial information: NCT02721459.
Is it possible to predict the prognostic values of Oncotype Dx using the results of web-based mathematical prognostic value models?
Authors: Tsuguo Iwatani, Koichiro Tsugawa
Journal: Journal of Clinical Oncology (2019)

e12058 Background: The goal of the study was to determine whether the prognostic values for ER+ HER2- breast cancer can be calculated based on a test of gene expression profiles in tumors using Oncotype Dx or by entering clinicopathological factors into a web-based model. We evaluated the correlation between these results to shed light on whether the results from web-based models could serve as representative indices for Oncotype Dx. Patients: Two hundred two primary breast cancer patients whose prognostic value was evaluated using Oncotype Dx between May 2010 and October 2018 in St. Marianna University Hospital. Methods: The patients’ clinicopathological factors were extracted from their medical records. Then, the 5- and 10-year breast cancer-specific mortality rates were calculated using PREDICT (www.predict.nhs.uk/tool), while the 5–10 year distant recurrence rate was calculated using CTS5 (www.cts5-calculator.com/). The correlations with the Oncotype Dx prognostic values were evaluated by calculating the Spearman’s rank correlation coefficient, and JMP.ver13.0 (SAS Institute Inc., Cary, NC, USA) was employed for the analysis. Results: The patients’ median age was 49. There were 78 lymph node(LN)-negative patients and 124 LN-positive patients. For the disease stages, 51 patients were stage I, 99 patients were stage IIA, 41 patients were stage IIB, and 11 patients were stage III or above. All patients of the correlation between the Oncotype Dx recurrence score (RS) and the 10-year breast cancer-specific mortality rate was r = 0.1616. The correlation of LN-Negative patients of the 10-year distant recurrence rate between Oncotype Dx and CTS5 was r = 0.1768. The correlation of LN-Positive Cases of the 5-year distant recurrence rate between Oncotype Dx and CTS5 was r = 0.3374. The correlation of these cohort between the 5-year mortality rate from Oncotype Dx and PREDICT was r = 0.4298. Conclusions: There was no correlation between the Oncotype Dx RS and prognostic values calculated from web-based models, and there was also no correlation for prognostic values of lymph node-negative cases. However, there was a correlation for prognostic values of lymph node-positive cases, but the correlation was too weak to use the results from web-based models as representative indices for Oncotype Dx.
Modeled CA-125 kinetics during neoadjuvant chemotherapy for predicting the likelihood of optimal interval debulking surgery in ovarian cancer patients: Data from CHIVA trial (a GINECO study).
Authors: Patrick Robelin, Michel Tod, Olivier Colomban, Christophe Louvet, Jean-Pierre Lotz, Sophie Abadie Lacourtoisie, Michel Fabbro, Christophe Desauw, Nathalie Bonichon, Jean Emmanuel Kurtz, Philippe Follana, Marianne Leheurteur, Francesco Del Piano, Carol René Alliot, Gaetan De Rauglaudre, Isabelle Laure Ray-Coquard, Pierre Combe, Annick Chevalier, Florence Joly, Benoit You
Journal: Journal of Clinical Oncology (2019)

5546 Background: A pre-operative predictive biomarker of CC0 interval debulking surgery (IDS) likelihood would be helpful. The modeled CA125 elimination rate constant KELIM predicts OS in 1st line setting (You et al. Clin Cancer Res 2019). The predictive/prognostic values of KELIM regarding CC scores at IDS, and survivals, during neo-adjuvant chemotherapy were assessed. Methods: The data of the CHIVA randomized phase II trial, comparing carboplatin-paclitaxel +/- nintedanib before IDS (NCT01583322), were used. A semi-mechanistic model was built to describe CA125 longitudinal kinetics during the first 100 treatment days. The relationships between KELIM and IDS CC scores, PFS &amp; OS, were assessed with other major prognostic factors (grade, histology, GCIG CA125 response, FIGO stage, and arm) using multivariate logistic regression (logit), C-index &amp; survival tests. Results: The longitudinal kinetics of 529 CA125 values, assessed every 3 weeks during neo-adj chemotherapy, were modeled in 133 patients (out of 188). KELIM (as a continuous covariate) was the only significant predictive factor of CC0 IDS likelihood using multivariate analyses (OR = 12.37, 95% CI [4.32-39.67]). CC0 IDS probability can be estimated with patient KELIM: ≥ 90 % if standardized KELIM ≥ 0.12. Non-parametric survival models confirmed the independent predictive values of KELIM categorized by terciles regarding PFS &amp; OS (Table). The parametric model linking KELIM (as a continuous covariate) with OS allows to predict the patient survivals (months) based on their estimated KELIM (HR = 0.20, [0.10-0.39]). Conclusions: The prognostic &amp; predictive values of the modeled CA125 KELIM are also confirmed regarding CC0 IDS likelihood, PFS and OS with neo-adjuvant chemotherapy. Patient KELIM is calculable online, based on observed CA125 values, on http://www.biomarker-kinetics.org/ . Clinical trial information: 2011-006288-23. [Table: see text]
A digital oncology patient-reported outcomes platform: Building innovative electronic patient symptom assessments in epic mychart to improve the quality of life and survival of patients with advanced cancer.
Authors: Sidharth Anand, Anne Margaret Walling, Sarah F. DAmbruoso, Neil Wenger, Jennifer Singer, John A. Glaspy
Journal: Journal of Clinical Oncology (2019)

e18312 Background: Establishing a system to monitor patient reported outcomes (“PRO”) has been demonstrated to be essential for a well-functioning cancer system. Studies have shown that routine collection of PROs allows providers to address medical issues earlier and impacts a patient’s overall survival. Unmet needs for symptom management are prevalent in the cancer population, especially patients with advanced cancer. Approximately 35% of UCLA Hematology-Oncology patients with advanced cancer in 2016 presented to Emergency Rooms for symptom-related complaints such as nausea, pain, constipation, dehydration, and fatigue. We hypothesize that the creation of an electronic PRO platform through EPIC MyChart will ensure patients receive timely evaluation of their symptoms, resulting in improved quality of life, and decreased ER and hospital utilization. Methods: We developed an innovative PRO platform through Epic MyChart along with a Best Practice Advisory alert system to identify patients at risk for worsening symptoms, ER visits, and inpatient admissions. We then built an electronic version of the Edmonson Symptoms Assessment System, which providers can push to patients through Epic MyChart, with results stored within the Flowsheets section of Epic. We also built a passive alert using Epic’s Best Practice Advisory (“BPA”) system, to notify providers when a patient’s MyChart ESAS Assessment Scores have exceeded a defined threshold. Results: Preliminary data from surveys sent to a series of advanced cancer patients seen in an outpatient palliative oncology clinic over 1 month, demonstrated a 100% response rate (6/7) surveys completed when sent one week prior to patient’s being seeing in clinic, and 17% response rate (1/6) when sent two to three weeks prior to clinic visit. The average total ESAS score reported was 40, with average individual score of 4/10 for any given symptom. Conclusions: We will implement this electronic PRO platform in multiple oncology clinics at UCLA, and measure provider and patient satisfaction, completion rates, and monitor outcomes such as ED visits and inpatient admissions. We hope this system will lead to an overall survival benefit. This project demonstrates the potential of developing innovative PRO platforms through Epic MyChart and the importance of clinical workflows in the implementation process.
Sixty seconds on . . . hospital food
Authors: Zosia Kmietowicz
Journal: BMJ (2019)

Not likely. An audit of the eating habits of hospital staff, patients, and visitors has shown that they’re more likely to reach for sweets, crisps, and cake than the healthy options on offer.1

Only five of the top 20 snacks sold in six hospitals monitored by health psychologists for six weeks were healthy. The most unhealthy snacks were baked goods, with a mean 385 kilocalories, …
A phase 3 trial evaluating efficacy and safety of lenvatinib in combination with pembrolizumab in patients with advanced endometrial cancer.
Authors: Vicky Makker, Antonio Casado Herraez, Carol Aghajanian, Keiichi Fujiwara, Sandro Pignata, Richard T. Penson, Corina E. Dutcus, Matthew Guo, Lea Dutta, Robert Orlowski, Alan Smith, David S. Miller
Journal: Journal of Clinical Oncology (2019)

TPS5607 Background: Lenvatinib (LEN) is a multikinase inhibitor of vascular endothelial growth factor receptors 1–3, fibroblast growth factor receptors 1–4, platelet-derived growth factor receptor α, RET, and KIT. Pembrolizumab (PEMBRO) is a monoclonal antibody targeting programmed cell death receptor 1 (PD-1). Preliminary analyses of a phase 1b/2 study of LEN + PEMBRO showed promising antitumor activity and a manageable safety profile in advanced endometrial cancer (EC). Methods: A multicenter, randomized, open-label, phase 3 study (KEYNOTE-775/E7080-G000-309; clinicaltrials.gov NCT03517449) will evaluate efficacy and safety of LEN + PEMBRO vs treatment of physician’s choice (TPC) in patients with advanced EC. Patients must be aged ≥ 18 years, have advanced EC that progressed after 1 prior platinum-based therapy, have measurable disease per RECIST v1.1, and an Eastern Cooperative Oncology Group performance status ≤ 1. Patients must have mismatch repair (MMR) status confirmed by central laboratory via immunohistochemistry on archived or fresh tumor biopsy. ~780 patients (~120 MMR-deficient; ~660 MMR-proficient) will be randomized to receive LEN 20 mg orally once daily and PEMBRO 200 mg intravenously (IV) every 3 weeks (Q3W) or TPC. Patients will be randomized first according to MMR status; MMR-proficient patients will be further stratified by ECOG PS, geographic region, and prior history of pelvic radiation. TPC is either doxorubicin 60 mg/m 2 by IV Q3W or paclitaxel 80 mg/m 2 by 1-hour IV infusion weekly (3 weeks on/1 week off). The dual primary endpoints are progression-free survival (PFS; per RECIST v1.1 by blinded independent central review) and overall survival (OS). The PFS analysis will occur at the planned interim analysis (~363 OS events in MMR-proficient patients; ~524 PFS events), and the study will have 99% power to detect a hazard ratio (HR) of 0.55 with a 1-sided 0.0005 significance level. A final OS analysis will occur at 518 OS events, when the study will have 90% power to detect a HR of 0.75 with a 1-sided 0.0245 significance level. Secondary endpoints include objective response rate, health-related quality of life, safety and tolerability, and pharmacokinetics. Clinical trial information: NCT03517449.