tbuckley/cabot-search huggingface dataset:
A phase 2 study of PNT2258 in patients with relapsed or refractory (r/r) diffuse large b-cell lymphoma (DLBCL): An initial report from the Wolverine study.
Authors: Jason R. Westin, Michael B. Maris, Ayad M. Al-Katib, Nehal J. Lakhani, Prapti Arvind Patel, Wael A. Harb, Kelly McCaul, Dipti Patel-Donnelly, Richard Adam Messmann, Barbara J. Klencke
Journal: Journal of Clinical Oncology (2016)

TPS7577 Background: PNT2258, a liposomal encapsulated DNA interference (DNAi) oligonucleotide nanoparticle targeting the BCL2 oncogene, has demonstrated single agent activity with notable durability in a pilot study enrolling a broad spectrum of patients with B-cell malignancies including relapsed non-Hodgkin’s lymphoma (Harb WA, et al. Blood 2014 124:1716). We now report on a Phase 2 multicenter, Simon 2-stage study, in progress, of single agent PNT2258 (Wolverine [NCT02226965]) for subjects with r/r DLBCL. Methods: Up to 60 response evaluable patients with histologically confirmed DLBCL will receive 120 mg/m2 of PNT2258 on Days 1 – 5, every 21-days, for up to 8 cycles. Further treatment until progression, at an attenuated dose and schedule, is allowed for patients who continue to benefit. Eligibility requires FDG PET-CT positive and measureable disease, adequate organ function and prior exposure to CD20-targeted therapy, an alkylating agent, and corticosteroid. The primary objective is to assess overall response rate defined as the proportion of patients with complete or partial response according to the revised 2014 International Working Group (IWG) criteria for lymphoma (Lugano Classification, J Clin Oncol 32:27 3059-3067, 2014). Subject tumors are assessed centrally for cell of origin using the Lymph2Cx (NanoString) assay, as well as IHC assessment of BCL2, Ki-67, CD20, and MYC expression levels, and translocation status using FISH for MYC, BCL2 and BCL6. Final clinical response assessment will be based upon central (blinded) radiologic review. Enrollment continues in this multicenter Phase 2 DLBCL-specific trial. As of January 4 2016, 27 patients have been enrolled. Clinical trial information: NCT02226965.
Abstract 18560: Myocardial-specific Overexpression of GTP Cyclohydrolase 1 Prevents Diabetic Cardiomyopathy Independent of Nitric Oxide
Authors: Ricardo Carnicer Hijazo, Drew Duglan, Jillian N Simon, Surawee Chuaiphichai, Ashley Hale, Keith M Channon, Barbara Casadei
Journal: Circulation (2014)

Background: Diabetic cardiomyopathy is characterised by significant left ventricular (LV) diastolic dysfunction. Increased oxidative stress and reduced nitric oxide (NO) availability secondary to o...
A collaborative physician engagement strategy to reduce oncology care variation across a clinically integrated network.
Authors: Trever Bradley Burgon, Jon M. Richards, David R Paculdo, Diana Tamondong-Lachica, John Williamson Peabody
Journal: Journal of Clinical Oncology (2018)

e18807 Background: Health systems are looking to standardize care across the oncology care continuum. For standardization to lead to higher quality and lower costs, physicians must be actively involved in the process. Advocate Physician Partners (APP), a 5,000-physician CIN, has over 100 medical oncologists in 21 employed and independent practices. We describe a patient simulation-based project, which uses practice measurement and feedback to reduce unwanted variation in breast and lung cancer care across APP. Methods: We measured clinical performance using the Clinical Performance and Value (CPV) simulated patient platform. Responses from 123 APP medical oncologists were scored against evidence-based workup and treatment criteria. Providers received individual and group feedback on their care. This process repeated every 4 months, in 6 rounds, from Jan 2016 to Nov 2017. One of the goals of the project was to reduce unnecessary imaging for early stage breast cancer, which we analyzed in the CPVs as well as cancer registry and claims data. Results: In the CPVs, overall quality scores improved 21% (p<0.01), including increases of 39% in treatment (p<0.01) and 9% in diagnostic accuracy (p<0.01). Preferred guideline-based chemotherapy increased 27% (p<0.01). Early focus on palliative needs for late stage lung cancer increased 140% (p<0.01). Unnecessary test ordering declined 25% (p<0.01) and estimated costs fell 10%. Use rates of CT (p=0.04) and other scans (p=0.02) in early stage breast cancer decreased, showing better alignment with guidelines. We then analyzed the patient-level claims data and found they correlated with the CPV results, showing declines in potentially unneeded breast cancer testing. Conclusions: APP medical oncologists demonstrated increased adherence to evidence-based practices per the CPVs; this impact translated into registry/claims effects demonstrating decreased unnecessary imaging. Table. Stage I/II Breast Cancer Imaging Utilization. CPV Results Registry/Claims Results Scans Round 1 Round 6 Difference p-val Pre Post Difference p-val CT* 19% 9% -55% 0.04 30% 24% -20% 0.05 Other† 12% 5% -59% 0.02 7% 5% -21% 0.08 *Chest, Abdominal, Pelvic; †PET, Brain MRI or bone scan
Racial disparities in receipt of guideline care and cancer deaths for women with ovarian cancer.
Authors: Joan Warren, Kathleen A Cronin, Jennifer Stevens, Nadia Howlader, Edward Lloyd Trimble, Linda C Harlan
Journal: Journal of Clinical Oncology (2017)

e18081 Background: Receipt of guideline care improves survival for women with ovarian cancer yet care may vary by race. We assessed the receipt of guideline care and cancer deaths by race for women with incident ovarian cancer. Methods: This retrospective cohort analysis used the National Cancer Institute’s Patterns of Care data for black and white women diagnosed with all stages of ovarian cancer in 2002 and 2011 (n = 5356) with follow-up through 12/31/14. Data included patient characteristics, type of surgery and chemotherapy, and provider factors. Multivariate logistic regression was used to create the standardized percentages (predictive margins) of women receiving guideline treatment by race group. Cox proportional hazards models were used to assess the unadjusted and adjusted risk of ovarian cancer death by race. Results: At diagnosis, for black women, 35.6% had Stage III and 37.2% had Stage IV disease compared with 44.1% Stage III and 24.2% Stage IV for white women. More black women had surgery in large teaching hospitals (47.6%) than white women (39.7%) but use of gynecologic oncologists (GO) was similar for black women and white women- (62.1% vs 58.8%). In regression models, the standardized percent of black women receiving guideline care was significantly lower than for white women (29.2% vs 38.5%). The unadjusted hazards ratio (HR) for death was significantly higher in black women (HR = 1.32) yet after controlling for patient and provider factors and receipt of guideline care, black women did not have a significantly higher risk of death (HR = 1.08). Conclusions: Rates of guideline care are very low for all women with ovarian cancer, significantly more so for black patients. Low use of guideline care among black women cannot be explained by provider factors as a large percent of black women consulted a GO or received care in large teaching hospitals. Research is needed to address how to increase guideline care among black patients as we found that race was not associated with the risk of death when guideline care was included as a factor in multivariate survival models.
The Compassionate Use Advisory Committee (CompAC) for development of pre-approval access to investigational drugs.
Authors: Edith P. Mitchell, Arthur Caplan, Alison Bateman-House, Amrit Ray
Journal: Journal of Clinical Oncology (2017)

e18001 Background: In May 2015, CompAC was formed at NYU to provide guidance fairly and transparently on allocating a limited supply of , Daratumumab, to patients outside of clinical trials. Janssen, manufacturer of Daratumumab, was receiving numerous pre-approval requests for access to the drug. Daratumumab (Darzalex) was approved in the U.S. for treatment of patients with multiple myeloma who have received at least one prior therapy and approved by EMA for monotherapy. The SPR program was phased out based on country level approvals, with requests and submissions managed in a regulatory and legal environment.Methods: CompAC was 10 medical experts, bioethicists, and patient advocates; ethical and medical principles for review and process guidelines developed. Weekly meetings were held to consider SPR requests, with 3 members voting each week. After U.S. approval, requests for drug were considered only from countries where Janssen was seeking but had not gained approval. Recommendations were conveyed weekly for final decisions. Results: A total of 331 cases were received by Janssen of which 5 withdrew and 2 expired, leaving 324 cases for review. Of these, 180 were sent to CompAC and 163 were recommended by CompAC for treatment. Janssen approved all 163. CompAC recommended declining 17 of these cases; Janssen declined 15 (2 cases were approved based on additional information provided). Of the 144 patients excluded by Janssen before CompAC review, 27 were due to low benefit/risk profile, 17 provided incomplete clinical information, 42 for other variables, 46 received alternative therapies, 10 for referral to another pre-approval access channel, and 2 commercially available drug. Of the cases that CompAC recommended declining, 11 were due to low benefit/risk profile, for 3 alternative therapies available, and remaining 3 for miscellaneous reasons. Requests were received from 13 countries, the majority from outside the U.S.Conclusions: CompAC was successfully implemented and provided rapid review of SPR requests for pre-approval Daratumumab access. Janssen is extending CompAC to other relevant assets. Other companies are considering the model.
Alpha particle radium-223 dichloride (<sup>223</sup>RaCl<sub>2</sub> ) in high risk osteosarcoma.
Authors: Vivek Subbiah, Peter Meade Anderson, Kalevi Kairemo, Winston W. Huh, Vinod Ravi, Najat C. Daw, Neeta Somaiah, Robert S. Benjamin, David S. Hong, Gregory Ravizzini, Eric Rohren
Journal: Journal of Clinical Oncology (2016)

11029 Background: Radium-223 dichloride (223RaCl2 ) is an alpha-emitting radiopharmaceutical and calcimimetic that has intrinsic bone-targeting properties. It is now approved for bone metastases from prostate cancer. We hypothesized that 223RaCl2 can be safely administered to patients with osteosarcoma (OS) and early signals of response and resistance can be assessed by quantitative and qualitative correlative imaging studies and biomarkers. Methods: A dose-escalation trial of 223RaCl2 ( 50, 75, and 100 kBq 223RaCl2 /kg ) enrolled pts age 15y+ w advanced OS. Molecular imaging with technetium (Tc)-99m bone scan, FDG PET or sodium fluoride-18 (NaF) PET was done at baseline and at restaging. Results: Overall, 18 pts were enrolled, 15 males, 3 females, age ranging 15-71yrs. Subtypes of OS were osteoblastic in 7 pts, high grade NOS in 7, chondroblastic in 2, fibroblastic in 1, and giant cell in 1. Tumor locations included lesion in the spine (12 pts, 66%), pelvis (10 pts, 55%), ribs (9 pts, 50%), extremity (7 pts, 38%), and skull (2 pts, 11%). Pts received 1–6 cycles of 223RaCl2 ; cumulative doses varied from 6.84 MBq to 57.81 MBq. G3 thrombocytopenia was seen in 1 pt at dose level 3. NaF-PET identified mets in the liver, not avid on FDG PET. One pt had metabolic response in the FDG-PET and NaF PET. Four pts had mixed responses w decreased avidity of bone lesion but increased avidity of surrounding soft tissue lesion. One patient had response in the brain metastasis. A validated bone pain survey demonstrated a reduction in bone pain. The RP2D for using 223RaCl2 for osteosarcoma is 100 kBq/kg monthly. Conclusions: 223RaCl2 at twice the dose approved for prostate cancer was well tolerated. With the CNS response, we see the first clinical evidence of blood-brain barrier penetration of an alpha particle. Our results indicate that NaF-PET identifies OS lesions in unexpected sites (such as liver), which were not avid on FDG PET, highlighting a potential role for NaF PET in OS staging. Clinical trial information: NCT01833520.
Tolerability and antitumor activity of cemiplimab, a human monoclonal anti-PD-1, in patients with non-small cell lung cancer (NSCLC): Interim data from phase 1 dose escalation and NSCLC Expansion Cohort.
Authors: Victor Moreno Garcia, Emiliano Calvo, Maria Eugenia Olmedo Garcia, Marta Gil Martin, Raid Aljumaily, Kyriakos P. Papadopoulos, Lee S. Rosen, Petra Rietschel, Kosalai Kal Mohan, Jingjin Li, Elizabeth Stankevich, Tracey Rowlands, Minjie Feng, Matthew G. Fury
Journal: Journal of Clinical Oncology (2018)

e21057 Background: NSCLC accounts for ~85% of lung cancers; most patients (pts) are at an advanced stage at the time of diagnosis. Cemiplimab (REGN2810) is being investigated for the treatment of NSCLC, in addition to other indications (NCT02383212). Methods: In the dose escalation (DE) phase, enrolled pts with advanced malignancies with no alternative standard-of-care therapeutic option received cemiplimab monotherapy at 1, 3 or 10 mg/kg every 2 weeks (Q2W) for up to 48 weeks. In the NSCLC expansion cohort (EC 1), enrolled pts with advanced disease who had relapsed after, or were refractory to at least first-line therapy received cemiplimab 200 mg Q2W for up to 48 weeks. Tumor biopsies were performed at baseline, Day 29 and progression, if possible. Tumor measurements were performed every 8 weeks according to RECIST 1.1. Results: As of Sept 1, 2017, 21 pts with NSCLC (1 in DE at 1 mg/kg; 20 in EC 1) were enrolled; median age was 65.0 years (range, 50–82; 14 M/ 7 F); 81.0% had a ECOG performance status of 1, 19.0% of 0; 13/21 (61.9%) had a histology of adenocarcinoma. The most common treatment-related adverse events (TRAEs) were asthenia, pneumonitis, and rash (each n = 3, 14.3%). Each of the following ≥Grade 3 TRAEs occurred once: pneumonitis, diabetic ketoacidosis, and nephritis. Best response by central independent review was 0 complete response (CR), 6 partial response (PR), 6 stable disease (SD) or non-CR/progressive disease (PD), and 9 PD. Overall response rate (ORR = CR + PR) was 28.6% (n = 6/21). Duration of response exceeded 8 months in 5/6 responders. Disease control rate (ORR + SD) was 57.1% (n = 12/21). Continued disease control has been maintained after planned discontinuation of therapy at 48 weeks for 4 pts. Of the tissue available for PD-L1 testing, 11/17 pts had a tumor proportion score (TPS) of < 1%, 3 pts had a TPS of > 50%. Conclusions: Cemiplimab showed an acceptable safety profile and demonstrated antitumor activity in pretreated pts with NSCLC. Pivotal trials of cemiplimab as monotherapy or in combination with other drugs in pts with advanced NSCLC are currently enrolling (NCT03088540; NCT03409614). Clinical trial information: NCT02383212.
Long-term impact of head and neck cancer (HNC) and treatment on financial distress and employment of HNC survivors.
Authors: Elizabeth Marie Wulff-Burchfield, David G Schlundt, Kemberlee Bonnet, Emily Castellanos, Mary S. Dietrich, Barbara A. Murphy
Journal: Journal of Clinical Oncology (2017)

e21575 Background: Increasing HNC survival highlights the importance of understanding late biopsychosocial outcomes. Financial and occupational impacts of HNC remain unexplored, thus we undertook a qualitative analysis to identify themes and explore the impact of HNC/treatment on survivors’ financial health. Methods: Eligibility: Locally-advanced HNC who participated in an R0-1, NED, and &gt; 1 year post treatment. Ten of 12 eligible patients were interviewed. Topics queried: financial issues related to HNC/treatment, financial/insurance matters affecting treatment, impact of treatment on fiscal responsibilities, financial counseling, and late impact of HNC/treatment on work. Frequency distributions were used to summarize patient characteristics. Interviews were transcribed verbatim, double-coded, and organized into themes and subthemes. Results: 50% male, 100% Caucasian, 60% married, median age 64 years, and median time since treatment of 64 months. Most denied ongoing financial strain from HNC/treatment, citing mitigating factors of preparedness (e.g. preexisting savings), health/disability insurance, and marital status. Those with financial distress noted an income limited by savings or disability. None reported financially-related delays in care. However, 2 patients used free healthcare. Most denied impact of HNC/treatment on financial obligations, but a minority reported subsequent delays in dental care, paying credit card bills, and travel. Financial counseling was used by 4 patients; benefits included decreased stress, access to financial programs, and education. Healthcare providers were considered an important source of financial counseling. Not all patients returned to work; late effects (fatigue, cognitive changes) impaired work capacity for those who did. Limitations: Population may have been skewed by loss to follow-up of patients with financial toxicity that precluded ongoing medical follow-up. Conclusions: Long-term financial distress was limited in this cohort of HNC survivors. Preparedness, adequate insurance, marital status, and financial counseling attenuated financial impacts of HNC. For those returning to work, late effects may affect capacity.
Cabazitaxel in metastatic castration-resistant prostate cancer (mCRPC): Real-life use, effectiveness, safety, and quality of life (QoL) in the FUJI cohort.
Authors: Stephane Oudard, Karim Fizazi, Florence Joly, Florence Tubach, Magali Rouyer, Stéphanie Lamarque, Estelle Guiard, Aurélie Balestra, Clémentine Lacueille, Jérémy Jové, Cécile Droz-Perroteau, Annie Fourrier-Réglat, Nicholas Moore
Journal: Journal of Clinical Oncology (2018)

5025 Background: Cabazitaxel (CAB) was marketed in March 2012 in France, based on overall survival (OS) benefit in mCRPC in 2nd-line (2L) post-docetaxel (DOC). FUJI is a post-authorisation study of the real-life performance of CAB. Methods: FUJI is a multicenter (n = 42) cohort study describing OS, safety, QoL (using FACT-P) and pain (using BPI-SF) in mCRPC CAB initiators in real-life, included from Sept 2013 to Aug 2015 in a retrospective cohort (follow-up (FU) 18 mths), and from March 2016 to March 2017 in a prospective cohort (FU 6 mths). Results: The retrospective cohort included 401 pts (median age 70) with CAB in 2L (18%), 3L (39%), 4L (23%), or > 4L (20%). Treatments before CAB included DOC (100%), abiraterone acetate (ABI 77%), enzalutamide (ENZ 33%). Median CAB use was 3.4 mths. Median OS was 11.9 mths [95%CI, 10.1-12.9]. In multivariate analyses, factors associated with a shorter OS were: grade ≥ 3 adverse event (AE) (HR = 2.05 [1.53-2.73]), visceral metastases (HR = 1.98 [1.40-2.80]), polymedication > 5 drugs (HR = 1.74 [1.23-2.45]), > 5 bone metastases (HR = 1.74 [1.20-2.53]), disease progression during DOC (HR = 1.69 [1.13-2.53]) or within 3 mths of last DOC cycle (HR = 1.51 [1.07-2.14]), ≥3 drugs such as DOC, ABI, ENZ before CAB (HR = 1.39 [1.00-1.92]), and PSA ≥ 135 ng/ml (HR = 1.36 [1.01-1.82]). Factors associated with better OS were ≥ 10-yr cancer history before CAB (HR = 0.66 [0.46-0.96]), ≥ 6 mths from last DOC dose to CAB initiation (HR = 0.71, [0.52-0.97]). Grade ≥ 3 AEs occurred in 55%, mainly anaemia (27%), neutropenia (15%), febrile neutropenia (8%), renal failure (7%), septicaemia/septic shock (5%). The prospective cohort included 61 pts (median age 72) previously treated with DOC (98%), ABI (61%) and ENZ (61%). 49 pts were evaluable for QoL and 44 for pain. QoL improved in 41%, was maintained in 29%, and deteriorated in 38%. 25% had pain decrease ≥ 1 level, 50% were stable and 25% increase ≥ 1 level. Conclusions: Real-life median OS in FUJI was lower than in TROPIC (11.9 vs. 15.1 mths), but very few FUJI pts would have satisfied TROPIC inclusion criteria. There were no new safety issues. Improved/stable QoL and pain were reported by 70% and 75% of pts treated by CAB, respectively.
Safety and clinical activity of durvalumab monotherapy in patients with hepatocellular carcinoma (HCC).
Authors: Zev A. Wainberg, Neil Howard Segal, Dirk Jaeger, Kyung-Hun Lee, John Marshall, Scott Joseph Antonia, Marcus Butler, Rachel E. Sanborn, John J. Nemunaitis, Cheryl Ann Carlson, Richard S. Finn, Xiaoping Jin, Joyce Antal, Ashok Kumar Gupta, Christophe Massard
Journal: Journal of Clinical Oncology (2017)

4071 Background: Durvalumab, an anti-PD-L1 mAb, has shown early and durable clinical activity with manageable safety in an ongoing Phase 1/2, multicenter, open-label study in pts with advanced solid tumors. Interim analyses from the HCC cohort in the dose-expansion part of this study are reported here. Methods: Patients with HCC (Child-Pugh class A) received durvalumab 10 mg/kg i.v. q2w for 12 months or until confirmed progressive disease, whichever occurred first. The primary objective was to evaluate the safety profile; secondary objective was to assess the antitumor activity (investigator-assessed RECIST v1.1). Clinical activity was evaluated for the total HCC population and by viral status. Results: As of Oct 24 2016, 40 HCC pts with median 23.9 (range 2.4–34.7) weeks follow-up received durvalumab. 93% had prior sorafenib. Treatment-related AEs occurred in 80.0% of pts, most commonly fatigue (27.5%), pruritus (25.0%) and elevated aspartate aminotransferase (AST) (22.5%). Grade 3–4 treatment-related AEs were reported in 20.0% of pts, most commonly elevated AST (7.5%) and elevated alanine aminotransferase (5.0%). 7 (17.5%) pts completed the initial 12-month treatment and 7 (17.5%) pts discontinued treatment because of an AE (none related to treatment). There were no deaths due to treatment-related AEs. Clinical activity is presented in the table. 4 pts achieved a PR; 2 were ongoing at data cut-off. Conclusions: Durvalumab had an acceptable safety profile and showed promising antitumor activity and OS in pts with HCC, particularly HCV+ pts. Clinical trial information: NCT01693562. [Table: see text]