tbuckley/cabot-search huggingface dataset:
Updated results from the enfortumab vedotin phase 1 (EV-101) study in patients with metastatic urothelial cancer (mUC).
Authors: Jonathan E. Rosenberg, Srikala S. Sridhar, Jingsong Zhang, David C. Smith, Joseph D. Ruether, Thomas W. Flaig, Joaquina Celebre Baranda, Joshua Michael Lang, Elizabeth R. Plimack, Randeep S. Sangha, Elisabeth I. Heath, Jaime R. Merchan, David I. Quinn, Sandy Srinivas, Matthew I. Milowsky, Chunzhang Wu, Elaina M. Gartner, Amal Melhem-Bertrandt, Daniel Peter Petrylak
Journal: Journal of Clinical Oncology (2018)

4504 Background: Patients (pts) with mUC are in need of novel therapies. Enfortumab vedotin (EV) is an antibody–drug conjugate that delivers a microtubule-disrupting agent to tumors expressing Nectin-4, a protein overexpressed in most urothelial cancers. Preliminary results of the EV-101 study (NCT02091999) suggest EV is active and tolerable at the RP2D of 1.25mg/kg; updated results from pts with mUC treated at RP2D are reported. Methods: Patients with mUC treated with ≥1 prior chemotherapy or who were ineligible for cisplatin received a 30-min infusion of EV on Day 1, 8, and 15 of each 28-day cycle. The primary objective was tolerability; antitumor activity (per RECIST v1.1), assessed by investigators every 8 wk, was a secondary objective. Results: As of 11 Jan 2018, 155 pts with mUC have been enrolled; 112 received EV at RP2D (median age 67 yr [range 24–86]). Bladder was the primary tumor site in 84 pts (75%) and 32 (29%) had liver metastases (LM). Ninety-one pts (81%) received prior platinum chemotherapy; 67 (60%) received ≥2 prior therapies in the metastatic setting, including 84 (75%) who had a checkpoint inhibitor (CPI). Consistent with previous reports, EV was generally well tolerated. Grade ≤2 fatigue (50%) was the most commonly reported treatment-related AE (TRAE). The most common Grade ≥3 AEs, regardless of attribution, were anemia (7%), hyponatremia (6%), urinary tract infection (6%), and hyperglycemia (5%). Four pts experienced a fatal TRAE (respiratory failure, urinary tract obstruction, diabetic ketoacidosis, multi-organ failure). Confirmed CR and PRs were observed in 3 and 34 pts, respectively; ORR = 33% (95% CI 24.7–42.9). Eight unconfirmed PRs were pending assessment. Additionally, ORRs in study subpopulations were 32% (prior CPI, n = 84), 37% (CPI naïve, n = 27), and 26% (LM/prior CPI, n = 23). Overall median DOR was 24.3 wk (95% CI 16.3–47.3) and PFS was 23.1 wk (95% CI 20.1–24.1). Median OS was 12.5 mo (95% CI 8.1–14.8) with 76 pts (68%) censored and OS at 6 mo was 75.1%. However, time-to-event endpoints continue to evolve. Conclusions: Enfortumab vedotin has encouraging ORR and PFS in heavily pretreated pts with mUC, including pts with LM and prior CPI treatment. Survival data awaits maturity. Clinical trial information: NCT02091999.
Abstract 18066: What Empowers Trained Bystanders to Initiate and Perform Cardiopulmonary Resuscitation?
Authors: Carolina Malta Hansen, Simone M Rosenkranz, Fredrik Folke, Line Zinckernagel, Tine Tjørnhøj-Thomsen, Christian Torp-Pedersen, Kathrine B Søndergaard, Graham Nichol, Morten H Rod
Journal: Circulation (2015)

Introduction: Cardiopulmonary resuscitation (CPR) training has been implemented widely across communities but little is known about what empowers trained bystanders to initiate and perform CPR. We sought to identify which factors that empower bystanders to initiate and perform CPR. Methods: From January 2012-April 2015, we conducted 128 semi-structured qualitative telephone interviews with bystanders to consecutive out-of-hospital cardiac arrests (OHCA) in Denmark. Purposive maximum variation sampling was used to select interviews and capture a wide range of perspectives using the following characteristics: (1) diverse demographics, (2) location of OHCA, (3) type of initial contact with OHCA, (4) resuscitation attempt alone or with others. Interviews were included until data saturation was reached. We used NVIVO software (QSR International Pty Ltd, Doncaster, VIC) to conduct in-depth qualitative thematic analysis. According to these methods, a small size is common because study validity is based upon the information richness of the selected participants rather than reaching a representative sample. Results: Bystander characteristics are shown in Table 1. Among bystanders previously trained in CPR, the following were described as empowering to initiate and perform CPR: (1) knowledge that intervention cannot cause harm and is decisive to improve survival, (2) the ability to work with other bystanders, (3) bystander leadership skills, (5) use of a ventilation mask and (6) use of an AED. Conclusions: Trained bystanders were empowered by: knowing the intervention could not cause harm and was decisive to improve survival; their leadership skills and ability to work with others; using a ventilation mask and an AED. Promoting these conditions through CPR courses, emergency dispatcher instructions as well as access to ventilation masks and AEDs is likely to increase bystander CPR rates. Implementing compression-only CPR may increase bystander CPR rates.
Geriatric comanagement and surgical outcomes of older cancer patients.
Authors: Armin Shahrokni, Saman Sarraf, Koshy Alexander, Sung W. Sun, Soo Jung Kim, Heidi Yulico, Sincere McMillan, Robert J. Downey, Beatriz Korc-Grodzicki
Journal: Journal of Clinical Oncology (2018)

10035 Background: Perioperative Geriatric Comanagement may improve surgical outcomes of older frail cancer patients. We present our 3 year experience with perioperative geriatric comanagement & the electronic Rapid Fitness Assessment (eRFA) at Memorial Hospital (MH). Methods: Since 2015, MH surgical services referred cancer patients age 75+ to the Geriatrics Service for preoperative evaluation including the eRFA (Shahrokni et al, JNCCN, Feb 2017). The eRFA score (0 to 13) is based on 1 point for impairments in the Karnofsky Performance scale score, dependency for basic and instrumental activities of daily living, Timed Up and Go test, history of fall, limited social activity, poor social support, presence of distress, depression, and cognitive impairment, polypharmacy, weight loss, and > 4 comorbid conditions. These patients were then co-managed by the geriatrics and surgical services while hospitalized. We compared the short- and long-term surgical outcomes of frail patients with fit patients. Results: 2291 patients (median age 79) had perioperative geriatric comanagement in 2015-17 with 1175 (51.3%) requiring hospitalization after surgery (average length of stay = 7days). The median eRFA score was 5 (IQR 3-8). 30 day minor & major surgical complications, emegrnecy room visit, readmission & mortality did not differ between frail patients (eRFA > 5) & fit patients (eRFA ≤5) in both the in- and out-patient surgical groups. Among patients requiring hospital stay, frailty was associated with a longer average length of stay (frail vs. fit; 7.7 vs. 6 days, P < 0.001). Frailty was associated with the higher likelihood of dying in 12 months after outpatient surgical procedure (OR = 5.27, p < 0.001) or inpatient surgical procedure (OR = 2.20, p = 0.002). Conclusions: Perioperative comanagement by geriatricians & surgeons leads to similar short term outcomes between frail and fit patients. Future studies should assess the impact of prolonged geriatric comanagement on long-term outcomes of older cancer patients after surgery.
Identifying risk factors for toxicity in patients (Pts) with hormone-receptor positive (HR+) advanced breast cancer treated with bevacizumab plus letrozole: A CALGB 40503 (Alliance) correlative study.
Authors: Daneng Li, Maura N. Dickler, Linda Mackie McCall, Olwen Mary Hahn, Clifford A. Hudis, Harvey Jay Cohen, Hyman B. Muss, Karla V. Ballman, Eric P. Winer, Debu Tripathy, Bryan P. Schneider, Constance T. Cirrincione, William Thomas Barry, Arti Hurria
Journal: Journal of Clinical Oncology (2016)

10047 Background: In HR+ advanced breast cancer, a progression free survival benefit was reported with the addition of bevacizumab (B) to first-line letrozole (L). However, increased B-related toxicity was observed. In addition to chronologic age, we hypothesized that measures of functional age could be used to identify pts at risk for toxicity while receiving L+B for HR+ advanced breast cancer. Methods: As part of the multicenter phase III trial CALGB 40503, pts with HR+ advanced breast cancer planned for treatment with L+B were approached to complete a pretreatment assessment questionnaire, consisting of validated instruments to evaluate physical function along with comorbidity, cognition, psychological state, social support and nutritional status. Pts were followed during treatment to capture grade ≥ 3 adverse events (AEs) as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0. The relationship between pretreatment assessment measures and the incidence of AEs was determined. Results: A total of 112/187 (60%) pts treated with L+B completed the pretreatment assessment questionnaire. Frequently reported grade ≥ 3 AEs were hypertension (26%), pain (20%), and proteinuria (7%). One hemorrhage and 1 thrombosis event occurred. Older age (p = 0.0035), decreased vision (p = 0.036), and physical function measures (lower activities of daily living scores [p = 0.023], lower instrumental activities of daily living scores [p = 0.023], limitations in climbing flights of stairs [p = 0.016], walking more than one mile [p = 0.041], and needing help getting to places out of walking distance [p = 0.02]) were all found on univariate analysis to be significantly associated with increased incidence of grade ≥ 3 AEs in pts receiving L+B. Conclusions: Older age, decreased vision, and impairment in physical function correlate with increased incidence of toxicity in pts receiving L+B. Incorporation of functional age assessment measures should be used to identify pts at serious AE risk in clinical trials. Support: U10CA180821, U10CA180882, UG1CA189823. Clinical trial information: NCT00601900.
Lymphocyte-to-monocyte ratio for predicting gemcitabine containing chemotherapy outcomes in pancreatic cancer patients.
Authors: Liwei Wang
Journal: Journal of Clinical Oncology (2016)

e15720 Background: Pancreatic dual adenocarcinoma (PDAC) exhibits intrinsic chemoresistance and it has great significance to predict the sensitivity of an individual to chemotherapy. The aim of the present study was to evaluate the superiority of the lymphocyte-to-monocyte ratio (LMR) in predicting chemotherapy outcomes in PDAC patients. Methods: We retrospectively reviewed the records of pancreatic cancer patients who received chemotherapy in Shanghai General Hospital. The LMR was calculated before chemotherapy and the optimal cutoff value of 3.55 was identified by generating receiver operating characteristics (ROC) curve. We classified the patients into two groups (group A, LMR > 3.55; group B, LMR < 3.55). We investigated the correlations between the LMR and clinicopathological parameters. Survival analysis was performed using the Kaplan-Meier method and log-rank tests. Cox regression model was used to investigate factors with independent prognostic value. Results: LMR was found to be correlated with ECOG, TMN stage, body weight loss, chemotherapy, pretreatment neutrophil and D-dimer (P < 0.05 for all). Overall survival (OS) was significantly longer in group A than group B (11.2 vs 6.6 months, P = 0.007). LMR was an independent prognostic factor for OS in the whole group (HR, 0.65; 95%CI, 0.42-0.99; P = 0.05). In the subgroup analysis, LMR remained to be an independent predictor in the group of patients who received gemcitabine containing chemotherapy (HR, 0.57; 95%CI, 0.34-0.95; P = 0.03) while it showed no prognostic value in PDAC patients who received other kinds of chemotherapy (P = 0.95). Conclusions: A higher pretreatment LMR is an independent prognostic factor for longer OS in PDAC patients, especially those who received gemcitabine containing chemotherapy.
Patient preference-weighted assessments using the ASCO value framework in recurrent, platinum-sensitive ovarian cancer.
Authors: Jonathan Foote, Margaret Liang, Angeles Alvarez Secord, David E. Cohn, Laura Jean Havrilesky
Journal: Journal of Clinical Oncology (2016)

6630 Background: The ASCO value framework allows comparisons of cancer treatments based on Net Health Benefit (NHB) and cost. We aimed to assess the value of treatments for recurrent, platinum-sensitive ovarian cancer using patient-assigned importance weights to NHB. Methods: 30 patients prospectively enrolled in a preferences study assigned ‘tokens of importance’ to each component of NHB (clinical benefit, toxicity, symptom palliation, and treatment free interval), and to components of clinical benefit (OS, PFS, RR). Patient-preference weights were scaled to reflect point totals utilized in the ASCO framework. Using patient- and ASCO-assigned weights, value assessments of available treatments for recurrent ovarian cancer were constructed: chemotherapy + bevacizumab (CMB), carboplatin + liposomal doxorubicin (CD), and maintenance olaparib (MO). NHB were presented alongside additional cost of novel therapy and a ‘benefit-cost ratio’ (NHB per additional cost). Results: Patient-weighted (P) versus expert-assigned (E) NHB component totals were: clinical benefit: 77 vs 80; toxicity -14 to +14 vs -20 to +20; symptom palliation: 26 vs 10; TFI: 18 vs 20. Clinical benefit component totals were OS: 15 vs 16, PFS: 10 vs 11, RR: 14 vs 8. Patient-weighted NHB/cost were: CMB: 20/$7,245; CD: 19/$2,692; and MO: 16/$8,400. Benefit-cost ratio of novel therapies was: CMB 0.003; CD 0.007; MO 0.002. Conclusions: P- and E-value assessments are similar. The value of maintenance regimens for recurrent ovarian cancer is limited by toxicity and cost. Comparison of ASCO- and patient-weighted NHB of recurrent ovarian cancer treatments. Regimens ASCO NHB Patient NHB Additional cost of novel therapy* Patient-weighted Benefit-Cost Ratio Total Components Total Components Chemotherapy +/- bevacizumab (OCEANS) CB (PFS) 22 22 CB (PFS) 20 20 $7,245 0.003 TS 0 TS 0 PB 0 PB 0 TFI 0 TFI 0 Carboplatin + liposomal doxorubicin (CALYPSO) CB (PFS) 11 21 CB (PFS) 10 19 $2,692 0.007 TS 0 TS 0 PB 0 PB 0 TFI 10 TFI 9 Maintenance olaparib (Study 19) CB(PFS) 33 13 CB (PFS) 30 16 $8,400 0.002 TS -20 TS -14 PB 0 PB 0 TFI 0 TFI 0 CB = clinical benefit; TS = toxicity score; PB = palliation bonus; TFI = treatment free interval *Compared to standard in RCT.
Association between changing body composition after diagnosis and survival of patients with advanced pancreatic cancer.
Authors: Michael Hayden Rosenthal, Ana Babic, William R Bamlet, Naoki Takahashi, Morales-Oyarvide Vicente, Natalia Khalaf, Lauren K. Brais, Marisa Welch, Caitlin Zellers, Laura Denai, Matthew Vander Heiden, Clary Clish, Gloria M. Petersen, Brian M. Wolpin
Journal: Journal of Clinical Oncology (2018)

e16247 Background: Body composition has been established as a proxy for the metabolic state of cancer patients and is associated with survival. Pancreatic adenocarcinoma is linked to both diabetes and cachexia. This study seeks to explore the associations between changes in body composition during treatment and outcomes in patients with advanced pancreatic cancer. Methods: 165 patients with locally advanced or metastatic pancreatic cancer were enrolled at two centers. All patients had available baseline CT imaging and stored plasma samples prior to receiving treatment, including surgery, radiation or chemotherapy. All patients had available follow-up CT imaging obtained 50-120 days after the baseline scan. Muscle, visceral fat and subcutaneous fat areas were measured using Slice-O-Matic software at the third lumbar vertebral body using clinical CT imaging data. Association between body composition rate of change and patient survival was evaluated using multivariate Cox proportional hazards regression. Association between patient characteristics and post diagnosis body composition change was evaluated using multivariate linear regression models. Results: The cohort had a mean age at diagnosis of 62.9 years, was 42% female, and was most commonly treated with FOLFIRINOX (36%), gemcitabine (32%), or gemcitabine doublet (11%). Median survival time was 11.4 months, including 14.8 months for locally advanced cases (35%) and 10.2 months for metastatic cases (65%). Mean percent change per 30 days was -3.7% for muscle area, -2.8% for muscle attenuation, -5.3% for subcutaneous fat, and -2.5% for visceral fat. Higher rates of decrease in muscle area and muscle density were associated with significantly shorter overall survival (p = 0.03 for muscle area trend across quartiles; p = 0.002 for muscle attenuation trend). The rates of change of subcutaneous and visceral fat areas were not associated with survival (p = 0.45 and 0.13). Duration of treatment was not significantly associated with change in muscle area or attenuation (p > 0.10 for all). Conclusions: Decreases in muscle area and attenuation during initial treatment for pancreatic cancer are associated with decreased overall survival.
Toxicity profile of patients with gynecological cancers (Gyne) enrolled in phase I trials.
Authors: Yeh Chen Lee, Lisa Wang, Elise C. Kohn, Lawrence Rubinstein, S. Percy Ivy, Pamela Harris, Stephanie Lheureux
Journal: Journal of Clinical Oncology (2018)

5572 Background: Gyne patients enrolled in Phase I trials may be at increased risk of certain toxicities given their extent of abdominal disease and prior treatments (surgery, chemo and radiotherapy). This study aims to assess the toxicity profile of patients with and without gyne cancers enrolled in Phase I trials. Methods: A retrospective review of the National Cancer Institute Phase I database was conducted with trials enrolling at least 1 gyne patient over a 16-year period (1995-2015). Eligible patients required complete data collection from baseline to end of trial participation. Adverse events (AEs) were categorized by CTCAE. Each AE was counted one time and analyzed based on highest grade and drug attribution. Results: 4,269 eligible patients enrolled in 150 Phase I trials were identified and divided into 3 groups: 1) females with gyne cancer (n = 685); 2) females with non-gyne cancer (n = 1698); 3) males (n = 1886). Median age in each group was 56 vs 56 vs 60 years, respectively. Mean total AEs reported during treatment was highest for females with gyne cancer [mean (standard error of mean [SEM]): 17.1 (0.4) vs 14.7 (0.2) vs 13.5 (0.2)], despite being similar at baseline [mean (SEM): 7.0 (0.2) vs 7.4 (0.1) vs 7.0 (0.1)]. Differences were predominantly due to greater abdominal-related AEs, infection and myelosuppression in females with gyne cancer. Drug-related AEs were also highest for females with gyne cancer [mean (SEM): 8.3 (0.2) vs 6.9 (0.1) vs 6.2 (0.1)]. Grade 3-5 AEs were similar [mean (SEM): 2.3 (0.1) vs 2.3 (0.1) vs 2.1 (0.1)]. Discontinuations due to AEs were similar (9% vs 9% vs 10%) and deaths during treatment were higher in males (2% vs 2% vs 4%). Regarding study outcomes, females with gyne cancer remained on treatment marginally longer (4.3 vs 3.3 vs 3.1 cycles) and achieved higher objective response rates (11% vs 6% vs 3%). Conclusions: Gyne patients enrolled in Phase I trials experienced greater abdominal-related AEs and infection, thus warranting specific consideration. However, grade 3-5 AEs and discontinuations were similar in all groups, suggesting that toxicities were low-grade and did not compromise outcomes.
Phase I-b study of isatuximab + carfilzomib in relapsed and refractory multiple myeloma (RRMM).
Authors: Ajai Chari, Joshua Ryan Richter, Nina Shah, Sandy Wai Kuan Wong, Sundar Jagannath, Hearn J. Cho, Noa Biran, Jeffrey Wolf, Samir S. Parekh, Pamela N. Munster, Deepu Madduri, Frank Campana, Thomas G. Martin
Journal: Journal of Clinical Oncology (2018)

8014 Background: Isatuximab (ISA) is an anti-CD38 mAb with potent anti-myeloma effects as monotherapy or together with lenalidomide (Len) + dexamethasone (d) in RRMM. Carfilzomib (K) is a proteasome inhibitor approved for use in RRMM as a single agent or in combination (Kd or LenKd). Objectives: The primary objective was to assess the maximum tolerated dose (MTD) of ISA + K in RRMM. Secondary objectives were assessment of safety, PK, immunogenicity, and efficacy (IMWG response criteria (ORR)). (NCT02332850) Methods: Eligible patients (pts) had disease progression after 2 prior lines, an ECOG < 3, and adequate organ function. A 3+3 dose escalation (DE) design was utilized. 3 dosing levels (DL) were tested: ISA 10 mg/kg Q2W, ISA 10 mg/kg QW x 4 then Q2W and ISA 20 mg/kg QW x 4 then Q2W in combination with K standard dose (27 mg/m2) and schedule. An expansion cohort (EC) of 18 pts was enrolled at DL2. Results: 15 pts were treated in DE and 18 in the EC. The median age (n = 33) was 61 yrs (range 39-79). Pts received a median of 3 (2-8) prior lines. All pts were IMid and PI exposed: 26/29 Len refractory (Refr), 21/29 Vel Refr, 13/29 Pom Refr and 8/11 K Refr. Median follow-up is 6.5m (0.5 – 24m). 29 pts are evaluable for response. ORR = 66% (1 sCR, 7 VGPR, 11 PR) and CBR is 86%. The median progression free survival has not been reached. Disposition: 15 pts have progressed (4 deaths from PD), 1 pt withdrew after 27 cycles and 17 remain on therapy. The median # of cycles given is 3 (range 1-27). No DLT or severe toxicity has been observed. Common adverse events (AEs-all grades, incidence ≥ 15%), were thrombocytopenia (66%), pain (60%), upper respiratory infection (56%), diarrhea (40%), fatigue (40%), anemia (33%), cough (33%), elevated creatinine (30%), nausea (30%), neutropenia (27%), headache (27%), dyspnea (16.7%) and fever (16.7%). Serious AEs occurred in 9pts and < 5% of AEs were Gr 3/4. Infusion reactions (IRs) were the most common ISA-related AE: 17 IRs in 16/32 pts (50%: Gr 1 (9) + Gr 2 (8)). Conclusions: Combining ISA and K appears safe; toxicity is c/w the AEs of the individual agents with few G3/4 AEs. Encouraging anti-MM activity (ORR 66%) was seen at all DLs. ISA 10 mg/Kg QW x 4 then Q2W dosing was selected for an ongoing Phase III trial of ISA + Kd versus Kd (IKEMA: NCT03275285). Clinical trial information: NCT-02332850.