tbuckley/cabot-search huggingface dataset:
Validation of an oncology-specific instrument to measure cancer patients’ perception of care coordination.
Authors: Izumi Okado, Kevin Cassel, Ian Pagano, Erin Fukaya, Timothy Kelleher, Tracey Hewitt, Randall F. Holcombe
Journal: Journal of Clinical Oncology (2019)

6543 Background: According to the IOM, effective coordination of care (CC) is a critical component of high-quality cancer care; however, lack of a reliable and validated measure limits our current understanding of cancer care coordination. We examined psychometric properties and utility of a Care Coordination Instrument (CCI), a survey developed to assess cancer patients’ perceptions of care coordination. Methods: The 29-item CCI was administered to 200 patients receiving active treatment for cancer at private oncology practices and hospital-based facilities from Oct. 2018 to Jan. 2019. The CCI includes subscales that evaluate CC in 3 domains (Communication, Navigation, Operational) across 4 areas of CC (patient-physician; between health providers; during inpatient-to-ambulatory care transitions; during transitions across different phases of care). All items were rated on a 4-point Likert scale. Results: Psychometric analyses of the CCI demonstrated that it has good internal consistency reliability (α = .917) and the three-factor solution was an acceptable fit (CFI = .853, SRMR = .065). Overall, cancer types (leukemia, myeloma) and having an identified patient navigator significantly predicted higher patients’ ratings of CC ( p &lt; .05). Similar trends were found for Communication and Operation subscale scores ( p &lt; .05). Having an identified navigator predicted higher Navigation scores ( p &lt; .05). Marginally significant differences were found for practice setting, with patients receiving care in hospital-based facilities reporting better CC ( p = .085). Item-level analyses revealed significant differences in specific aspects of CC (e.g., physician-patient communication) across cancer type, presence/absence of a patient navigator, and practice setting. Conclusions: The results demonstrate that the CCI is a reliable and valid instrument for measuring cancer patients’ perceptions of care coordination. Perception of CC correlated with the presence of a navigator, underlying cancer type and (trending) practice setting. Use of this instrument may reveal important information about cancer care coordination and may identify areas of targets for improvement in patient-centered cancer care delivery.
Role of advanced practice providers (APP) in meeting rising demands on oncology practices.
Authors: Bela Bapat, Yolaine Smith, Andrew Klink, Chadi Nabhan, Bruce A. Feinberg
Journal: Journal of Clinical Oncology (2019)

e18372 Background: The role of advanced practice providers (APPs), nurse practitioners (NPs) and physician assistants (PAs), is expanding in oncology for myriad reasons including improving access to care by closing the gap between demand for services and physician availability. This is especially true in oncology, where the shortage of oncologists and increasingly cited physician burnout is creating challenges for many practices and communities. Methods: We surveyed US physicians to understand their practices’ use of APPs, their role in patient treatment and support as well as their impact on practice workflow. Data were collected using web-based instrument between Sep 2018 and Nov 2018. Responses have been summarized using descriptive statistics. Results: Among 163 oncologists and hematologists surveyed, 74.2% (n = 121) employed NPs, 39.9% (n = 65) employed PAs, and 19.0% (n = 31) did not employ any APPs in their practice. Amongst practices that employed ≥1 APP (n = 132; 81.0%), over 40% of physicians reported a 1:3 APP: physician ratio. Most (62.1%) physicians stated that APPs only evaluated and saw returning patients, whereas 35.6% physicians used APPs to evaluate and see both new and return patients. More than 60% of physicians stated that APPs enhanced their practice efficiency, enabled physicians to focus more on complex patient cases, and made their workload manageable. By employing APPs, 52.3% of physicians were able to increase their patient caseload. The majority (57.6%) of physicians reported that they would employ more APPs in the next 3 years if resources were available, and 41.7% of physicians reported that APPs would likely take on additional responsibility in the next 3 years. Conclusions: Most community oncology practices in the US are employing APPs and are finding significant value in the APP roles by delegating various aspects of patient care to them. Most community practices are considering increasing the number of employed APPs and to expand the breadth of their responsibility. Integrating APPs into oncology practices is likely to have a larger impact on quality of patient care and potential mitigation of physician burnout.
Cost-effectiveness analysis of atezolizumab plus chemotherapy in the first-line treatment of extensive small cell lung cancer in China.
Authors: Lingyu Li, Hong Wang, Wenqian Li, Jiuwei Cui
Journal: Journal of Clinical Oncology (2019)

e20083 Background: Atezolizumab plus chemotherapy as a first-line therapy has shown significant survival benefits in patients with extensive small-cell lung cancer (SCLC). While, overprice limited its broad use in clinical. Here, the aim of this study was to evaluate the cost-effectiveness of atezolizumab plus chemotherapy in treatment of extensive SCLC as first line in China. Methods: A Markov model was established by extracting data from the IMpower 133 trial with untreated extensive SCLC patients. Utility values were obtained from published studies, and the costs were acquired from real world and literature. Additionally, sensitivity analyses based on a willingness-to-pay threshold (WTP) were performed to identify the uncertain parameters of Markov model. Results: Total costs of atezolizumab group was $183801, while cost of chemotherapy alone group was just $12920 in placebo group. The QLAYs in atezolizumab group was just 1.15 higher than that in placebo group (13.73 QALYs vs. 12.58 QALYs). The ICER between atezolizumab combination with chemotherapy and chemotherapy alone was $148592/QALY in China. The net benefit of placebo group was significantly higher than atezolizumab group. One-way sensitivity analyses highlighted that utilities of the PFS and PD state in placebo group were the most influential parameter. Conclusions: Atezolizumab combination therapy was not more cost-effective than chemotherapy alone therapy at a WTP threshold of $25929/QALYs in China.
Preliminary phase 2 clinical results of IL-15RαFc superagonist N-803 with BCG in BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) patients.
Authors: Karim Chamie, John H. Lee, Amy Rock, Peter R. Rhode, Patrick Soon-Shiong
Journal: Journal of Clinical Oncology (2019)

4561 Background: Patients with non-muscle-invasive bladder cancer (NMIBC) unresponsive to BCG therapy have limited treatment options. N-803 (also known as ALT-803) is an IL-15-based immunostimulatory protein complex (IL-15RαFc) that promotes proliferation and activation of natural killer (NK) cells and CD8+ T cells, but not regulatory T cells. Phase Ib data in BCG-naïve patients with NMIBC demonstrate that intravesical administration of N-803 with BCG induced complete response in all patients, without recurrences for the study duration of 24 months. Methods: An open-label, single-arm multicenter Phase 2 study of intravesical BCG plus N-803 in patients with BCG-unresponsive high-grade NMIBC (NCT03022825) was opened. The study has two cohorts: Cohort A, patients with BCG-unresponsive carcinoma in situ (CIS) [with or without Ta or T1 disease] and Cohort B, patients with BCG-unresponsive high-grade Ta/T1 disease. All treated patients receive intravesical N-803 plus BCG, similar to a standard induction and maintenance treatment schedule. The primary endpoint for Cohort A is incidence of complete response (CR) of CIS at any time, and the primary endpoint for Cohort B is disease-free rate at 12 months. Results: To date, forty-six patients have enrolled in this phase 2 trial (Cohort A (CIS), n = 23, Cohort B (Papillary), n = 23). Of eleven evaluable patients in Cohort A, nine patients (82%) have a reported CR. In addition, seven out of nine (78%) patients in Cohort A demonstrated CR at their 6-month response assessment. Of thirteen evaluable patients in Cohort B, ten patients (77%) showed no evidence of recurrence at their 3-month response assessment; of these, none (0/8) evaluated past 3 months have had disease recurrence. Three serious adverse events (AEs) have been reported (E coli infection, anemia, and bacteremia), with no immune-related AEs. Conclusions: Nine out of eleven (82%) patients with BCG-unresponsive CIS of the bladder demonstrated a complete response. Ten out of thirteen patients with BCG-unresponsive papillary NMIBC show no evidence of disease at first assessment. Intravesical N-803 plus BCG was well-tolerated and no patients experienced immune-related AEs. Clinical trial information: NCT03022825.
Pooled analysis of phase I dose-escalation and dose cohort expansion studies of IMP4297, a novel PARP inhibitor, in Chinese and Australian patients with advanced solid tumors.
Authors: Junning Cao, Pin Zhang, Paul L. de Souza, Bo Gao, Mark Voskoboynik, Dongmei Ji, Weina Shen, Sheng Yang, Yinglei Zhou, Rong Zhang, Jason D. Lickliter, Siao-Nge Hoon, David Palmieri, Suixiong Cai, Ye Edward Tian, Ning Ma, Cong Xu, Stone Yang, Shuaishuai Zhang, Binghe Xu
Journal: Journal of Clinical Oncology (2019)

3059 Background: Poly (ADP-ribose) polymerase (PARP) enzymes play critical roles in DNA damage detection and repair. IMP4297 is a novel, potent PARP1/2 inhibitor (IC 50 6.27nM/1.57nM) and has demonstrated to be 20-fold more potent than Olaparib in anticancer animal models. Two phase I studies were performed to evaluate and characterize the tolerability and safety, pharmacokinetics, and antitumor activity of single agent IMP4297 in Chinese and Australian patients with advanced ovarian, breast, prostate and other solid tumors. Methods: Dose escalation used a 3+3 design with a modified Fibonacci escalation. Dose cohort expansion was planned after efficacy was observed at the lowest dose level. Patients received IMP4297 monotherapy orally once a day until disease progression or unacceptable toxicity. Results: As of Jan 12, 2019, 56 patients, including 23 BRCA mutation carriers (BRCA+), had been enrolled at 2-100 mg dose level. No DLT was observed. In these two studies, the most frequent treatment-related adverse events (TRAEs) were leukopenia (20%), followed by anemia (18%), nausea (18%) and thrombocytopenia (14%). The majority of TRAEs were grade 1 or 2. Grade 3 TRAEs occurred in five patients (anemia, n=2; vomiting, n=1; thrombocytopenia, n=1; elevated AST, n=1). Only one patient had a dose reduction due to grade 3 thrombocytopenia. No serious TRAEs were observed. In 15 BRCA+ patients who had measurable lesions, the ORR was 33% and the DCR was 80%. There were 4 BRCA+, platinum-sensitive ovarian cancer patients with an ORR of 75% and a DCR of 100%. One patient with somatic BRCA mutated urothelial carcinoma showed a 76% decrease in tumor size. Conclusions: IMP4297 has been well-tolerated with significant anti-tumor activity. The 100 mg daily dose was selected as the RP2D based on safety, pharmacokinetics and clinical activity, and will be further characterized in dose expansion and phase II studies. Tumor response to treatment (RECIST 1.1) in patients with measurable lesions. Clinical trial information: NCT03508011 and NCT03507543. [Table: see text]
Pursuit of performance: An exploration of predictors associated with achieving performance based payments for breast cancer episodes under the Oncology Care Model.
Authors: Andrew Jehyun Song, Arianna Kee, Jared Minetola, Karen Walsh, Valerie P Csik, Amy Leader, Vittorio Maio
Journal: Journal of Clinical Oncology (2019)

e18035 Background: The Oncology Care Model (OCM) captures patient costs in a 6-month episode triggered by administration of systemic therapy. Most breast cancer (BC) patients will receive systemic therapy, with variations depending on stage and hormonal status, which makes BC an ideal indication to study costs in the OCM. Practices earn performance based payments (PBP) if aggregate episodic expenditures are managed below set target prices. We investigated predictors for episodic expenditures exceeding target prices, thus reducing potential for PBP. Methods: We identified BC episodes with non-decedent beneficiaries attributable to our academic medical center from OCM Reconciliation Reports during 7/1/16-6/30/17. Cohorts were defined as episodes whose costs were above target (Cohort 1) and those below (Cohort 2). The Wilcoxon Rank-Sum test was used to compare actual and target episode expenditure between cohorts. Multivariable logistic regression models were used to assess association of maintaining costs below target due to various predictors. Results: A total of 369 episodes were included in the study, with 124 episodes in Cohort 1 and 245 in Cohort 2. Median actual and target episode expenditures were higher in Cohort 1 (actual: $23,466 vs. $2,691, p &lt; 0.0001; target: $8,425 vs. $5,870, p &lt; 0.0001). In multivariable logistic regression, episodes were more likely to be below target if novel therapies, Part B drugs, or inpatient admissions were not utilized, controlling for other predictors (see Table). Conclusions: Large disparities exist for both actual expenditures and target prices for BC episodes in the OCM. Novel therapies, Part B drugs, and inpatient admissions are negatively associated with maintaining episode expenditures below target. Risk-adjustments for these expenditures need to be overhauled in OCM to accurately capture costs associated with management of cancer patients, and provide practical target prices for institutions to continue delivery of value based care. [Table: see text]
Nivolumab and ipilimumab treatment in prostate cancer with an immunogenic signature (NEPTUNES).
Authors: Yien Ning Sophia Wong, Peter Sankey, Debra Hannah Josephs, Robert J Jones, Simon J. Crabb, Sandy Beare, Marian Duggan, Laura White, Nikolaos Charlaftis, Graham Wheeler, Josep Linares, Sergio A. Quezada, Leah Ensell, Cliona Flanagan, Bihani Yoshana Kularatne, Moon Chung, Colin C. Pritchard, Alex Freeman, Teresa Marafioti, Mark David Linch
Journal: Journal of Clinical Oncology (2019)

TPS5090 Background: Responses to checkpoint inhibitor (CPI) monotherapy in patients with metastatic castration resistant prostate cancer (mCRPC) have been limited. This is in part attributed to low tumour mutational burden (TMB) and low tumour infiltrating lymphocytes (TILs). Previously ~20% patients with prostate cancer have demonstrated high TILs or TMB 1 . We hypothesize that patients with higher TMB due to mismatch repair deficiency (dMMR) or defective DNA damage response (dDDR) and patients with high TILs are more likely to respond to combination CPI with anti PD-1 and anti CTLA-4 therapy. Methods: NEPTUNES is a single arm phase II trial designed to assess the efficacy of nivolumab and ipilimumab in biomarker selected patients with mCRPC that have progressed following ≥1 line of therapy. The immunogenic signature (ImS) biomarker is defined by ≥1 of the following: 1) dMMR by immunohistochemistry (IHC); 2) dDDR detected by the UW-OncoPlex sequencing assay and; 3) high TILs on multiplexed IHC. The UW-OncoPlex assay detects mutations in &gt;260 genes and provides an estimation of TMB. Assuming an ImS+ rate of 20%, we aim to pre-screen 175 patients in order to enrol 35 patients into the main study. The primary endpoint is composite response rate (CRR), achieved if ≥1 of the following criteria are satisfied: 1) radiological response by RECIST 1.1; 2) PSA response ≥50%; 3) conversion of circulating tumour cells (CTC) count from ≥5 cells at baseline to &lt;5 cells at week 9. The treatment will be deemed ineffective if the CRR is &lt;20%. Nivolumab (1 mg/kg) and ipilimumab (3 mg/kg) is dosed every three weeks for up to 4 times, followed by a 480mg flat dose of nivolumab every 4 weeks for up to one year. Baseline biopsies are mandated and paired biopsy at week 12 is encouraged. The secondary endpoints include safety, overall survival, and radiological and PSA progression free survival. Exploratory biological markers including TMB, mutational profiles, change in TILs and liquid biomarkers will be correlated with the primary clinical endpoint. Since opening in February 2018, 126 patients have been pre-screened with 25 ImS+. To date, 9/25 ImS+ patients have been enrolled into the main study. The trial is ongoing, with patient accrual expected to complete by late 2019. References: 1 Linch, M., Goh, G., Hiley, C., Shanmugabavan, Y., McGranahan, N., Rowan, A., . . . Swanton, C. (2017). Intratumoural evolutionary landscape of high-risk prostate cancer: the PROGENY study of genomic and immune parameters. Ann Oncol, 28(10), 2472-2480. doi:10.1093/annonc/mdx355. Clinical trial information: NCT03061539.
Effect on tumor growth by TGF-β1/COX-2 siRNA combination product (STP705) in a human cholangiocarcinoma (HuCCT-1) xenograft tumor model in nude mice.
Authors: Michael Molyneaux, John Xu, David M. Evans, Patrick Lu
Journal: Journal of Clinical Oncology (2019)

e14652 Background: Cholangiocarcinoma (CCA) is a hepatobiliary cancer and although there have been advances recently there is a need for additional treatment methods for patients. Over expressions of TGF-β1 and COX-2 have been reported to play key roles in tumorigenesis of CCA. We studied the effect of STP705 on the growth of HuCCT-1 xenograft tumors in nude mice. STP705 is a TGF-β1/COX-2 specific siRNA combination product formulated in Histidine-Lysine co-Polymer nanoparticle delivery system. Methods: HuCCT-1 xenograft tumors were implanted subcutaneously into 24 BALB/c nude female mice (n = 8/group). Group 1 received vehicle control, group 2 (low-dose) received 8µg of STP705, and group 3 (high-dose) received 16µg of STP705. Intratumoral test article administration and tumor volume measurements were conducted twice a week for 3-weeks. Qualitative analysis was performed on H&amp;E, Picrosirius red (PSR) and immunohistochemistry (IHC) stained sections of tumor tissues. Results: High- and low- dose groups of STP705 reported significantly lower mean tumor volume at day 21 (p = 0.005 &amp; p = 0.036, respectively) as compared to control group. High-dose group reported significantly lower tumor volume at days 11 (p = 0.042), 15 (p = 0.003), and 18 (p = 0.007) as compared to the control group. IHC assessment demonstrated that STP705-treated animals had significantly lower (H-score ± SEM) TGF-β1, COX-2, HSP70, Bcl-xL and MMP-9 staining (52±9, 39±4, 178±8, 25±7 &amp; 7±1, respectively) as compared to control animals (94±11, 66±8, 213±7, 59±8 &amp; 11±2, respectively – with p &lt; 0.05). Assessment of Caspase-3 and H&amp;E (necrosis and inflammation) slides reported higher mean score for STP705-treated animals, while PSR staining reported lower fibroplasia for STP705-treated animals as compared to the control animals. Conclusions: The data suggests that STP705-treatment suppresses TGF-β1 and COX-2 expression resulting in inhibition of (i) tumor cell survival, (ii) fibrosis, (iii) promotes apoptosis, and (iv)decreased invasiveness of tumor cells. Overall, STP705 is an innovative siRNA-based treatment that results in significant suppression of tumor growth in a HuCCT-1 xenograft mouse tumor model.
Sequencing chemotherapy and immune checkpoint inhibitors (ICI) in metastatic urothelial carcinoma (UC): Meet-Uro1 study.
Authors: Marco Bandini, Elena Farè, Daniele Raggi, Ugo De Giorgi, Giuseppe Luigi Banna, Umberto Basso, Tania Losanno, Melissa Bersanelli, Sebastiano Buti, Daniele Santini, Claudia Mucciarini, Marcello Tucci, Rosa Tambaro, Azzurra Farnesi, Corrado Ficorella, Orazio Caffo, Emanuele Naglieri, Filippo Pederzoli, Sandro Pignata, Andrea Necchi
Journal: Journal of Clinical Oncology (2019)

e16013 Background: Several ICI are now approved in different therapeutic settings of metastatic UC. The identification of the optimal therapeutic sequence that includes standard chemotherapy (CT) use is a key objective of further research, mainly in the first-line (1L) setting. In this study, we analyzed the pathways of treatment post-ICI and focused on the effects of CT post-ICI in both 1L and salvage-line (≥2L) therapy of metastatic UC. Methods: Data from 15 Italian centers were collected. Patients (pts) should have received ICI in any line of treatment for metastatic UC and have experienced a disease progression (PD) according to RECIST 1.1. Cox regression analyses were performed within the subgroups, and adjusted Kaplan-Meier curves analyzed the progression-free survival (PFS) and overall survival (OS) post-ICI PD, according to the treatment line. Results: 278 pts (79 in 1L; 199 ≥2L) were analyzed. In total, after ICI, pts were treated with CT (N = 69), ICI beyond PD (N = 20) or no treatment (N = 189). Features associated with no therapy post-ICI were rapid PD on ICI (p &lt; 0.001) and number of metastatic sites (p = 0.002). The objective response (OR) to CT post-ICI was 23.1% in 1L, and 18.5% in ≥2L. Median PFS was 5 months (m) in 1L and 3m ≥2L, median OS on CT was 13m in 1L and 9m ≥2L. Post-ICI CT was not significantly associated with improved OS in 1L on multivariable analyses (MVA): HR: 0.43 (95%CI: 0.15-1.23), but it was significant in MVA in ≥2L pts (HR: 0.22, 95%CI: 0.10-0.48). The type of previous ICI (combination-ICI vs single-agent ICI, p = 0.789), as well as the OR to previous ICI (p = 0.871) had no effect on OS with sequential CT on MVA. In the total population adjusted by line, median OS post-CT was 17m (range 15-NA), and with ICI beyond PD was 8m (6-NA) (p &lt; 0.001). Conclusions: This large multicentric appraisal indicated that CT post-salvage ICI is endowed with similar activity and efficacy compared to ICI-naïve pts. Conversely, CT administered post-ICI in 1L determined less responses and was not significant on MVA. These effects are likely determined by the inability to rescue pts with rapidly aggressive disease. Shifting to salvage CT at the time of PD on ICI remains the preferable option in all suitable pts.