tbuckley/cabot-search huggingface dataset:
Disease, clinical, and treatment characteristics of patients (pts) with polycythemia vera (PV) enrolled in the REVEAL study.
Authors: Michael Richard Grunwald, Brady Stein, Alison Moliterno, Ralph V. Boccia, Stephen T. Oh, Ahmad Bilal Naim, Joseph A. Cordaro, Wei Peng, Hao Sun, Shreekant Parasuraman, Ruben A. Mesa
Journal: Journal of Clinical Oncology (2016)

e18557 Background: Limited real-world data exist about the burden of PV and treatment patterns in the US. REVEAL describes burden of disease, clinical management of PV, and patient-reported outcomes for US pts with PV. Methods: REVEAL is a prospective, observational study enrolling adults ≥ 18 years (y) with PV. Disease/clinical characteristics, treatment patterns, and patient-reported outcomes data are collected at usual-care visits over a 36-mo period. This updated analysis describes physician-reported disease/clinical characteristics and treatment patterns of currently enrolled pts (data cutoff, 13 Nov 2015). Results: 1687 pts were enrolled from 191 sites (academic n = 28; community n = 163). The primary methods of PV diagnosis were elevated Hgb, +JAK2V617F test, and low serum EPO level. Elevated WBC and platelets, and splenomegaly led to diagnosis in 19.9%, 29.3%, and 6.9% of pts, respectively. 44.1% of pts had ≥ 1 symptom that led to diagnosis; the most common symptoms were fatigue 21.7%, pruritus 13.1%, muscle aches/bone pain 8.4%, insomnia 5.7%, and night sweats 5.2%. 11.4% of pts had a history of thrombotic events (TE) at diagnosis. 5.9% had a family history of PV. At enrollment, median age was 67 y, 54% were male, 89.5% were white, 45.6% had smoked, 51.4% were retired, 32.6% were employed, and 4.3% were unable to work/disabled. Median disease duration was 4.3 y; 18.4% of pts were diagnosed < 1 y and 41.0% were diagnosed > 5 y before study entry. Mean hematocrit was 44.8%, Hgb was 14.4 g/dL, WBC count was 10.6×109/L, and platelet count was 782.8×109/L. At enrollment, 19.4% had a history of TE; 11.3% and 9.2% had ≥ 1 venous or arterial TE. The most common symptoms were fatigue 36.7%, pruritus 23.5%, headache 17.3%, insomnia 16.8%, dizziness 13.5%, dyspnea 12.9%, and bone pain 11.4%. Of pts who had spleen palpation data, 19.0% had splenomegaly. The most common PV treatments ± aspirin were phlebotomy (PHL, 32.1%), hydroxyurea (HU, 28.2%), and PHL + HU (24.5%). Conclusions: These data show that pts had a high symptom burden and TE rate at diagnosis that remained high at enrollment. Longitudinal data from REVEAL can provide better understanding of disease continuum, complications, and consequences of PV. Clinical trial information: NCT02252159.
Responses in patients with BRAF V600-mutant metastatic melanoma receiving anti-PD1/PDL1 therapy alone or combined with BRAF inhibitors.
Authors: Edelyn Barcena, VanAnh Trinh, Susan E McIntyre, Rinata Simien, Suzanne Cain, Adi Diab, Rodabe Navroze Amaria, Sapna Pradyuman Patel, Isabella Claudia Glitza, Hussein Abdul-Hassan Tawbi, Michael A. Davies, Wen-Jen Hwu
Journal: Journal of Clinical Oncology (2016)

9546 Background: Whether anti-PD1/PDL1 (anti-PD) therapy alone, or anti-PD combined with BRAF inhibitors (BRAFi) represents the best treatment for patients (pts) with BRAF V600-mutant metastatic melanoma (BMMM) remains unclear. Combination therapy has been attempted in practice to improve disease control in BMMM pts. We report our single-institution experience using anti-PD therapy both alone and in combination with BRAFi in BMMM. Methods: At MD Anderson Cancer Center, 457 metastatic melanoma pts (excluding uveal melanomas) received anti-PD therapy between November 2009 and December 2015. Among the 113 pts (25%) with BMMM, 34 (30%) pts were BRAFi-naïve and 79 (70%) were previously treated with BRAFi. These pts were separated into 4 cohorts based on exposure to BRAFi prior to anti-PD therapy (BRAFi naïve vs. treated) and whether anti-PD therapy was administered alone or in combination with BRAFi. Data were collected and analyzed for rates and duration of responses (RECIST v1.1) or disease stabilization. Results: See table. Conclusions: Our retrospective study showed anti-PD therapy alone had robust antitumor activity in pts with BMMM, regardless of prior BRAFi exposure.BRAFi-naïve pts appeared to achieve higher response rates with the combination of BRAFi and anti-PD therapy than with anti-PD therapy alone; however, the number of pts was small. BRAFi-treated pts derived less benefit from combined BRAFi and anti-PD therapy than from anti-PD alone. N (pts) CRs+PRs N (%) Median Response Duration mos (range) SDs N (%) Median Disease Control Duration mos (range) BRAFi-naïve/anti-PD alone 14 5 (36) 25 (3+-34+) 7 (50) 5 (2+-7+) BRAFi-naïve/anti-PD+BRAFi 20 10 (50) 9 (3-29+) 8 (40) 5 (2-10+) BRAFi-treated/anti-PD alone 38 12 (32) 15 (7+-34+) 18 (47) 8 (3-18+) BRAFi-treated/anti-PD+BRAFi 41 5 (12) 8 (7+-15+) 26 (63) 7 (2-16+)
A phase 1 study evaluating the safety, pharmacology and preliminary activity of MM-310 in patients with solid tumors.
Authors: Marc S. Ernstoff, Wen Wee Ma, Frank Yung-Chin Tsai, Pamela N. Munster, Tian Zhang, Walid Kamoun, J. Marc Pipas, Sharon Chen, Sergio Santillana, Vasileios Askoxylakis
Journal: Journal of Clinical Oncology (2018)

TPS2604 Background: Ephrin receptor A2 (EphA2) is expressed in cancer and stroma cells in a wide range of solid tumors. MM-310 is an EphA2-targeting liposomal form of a docetaxel prodrug. Preclinical investigation revealed a high correlation between EphA2 expression on cancer cells and MM-310 uptake. In vivo studies in multiple xenograft models demonstrated superior antitumor activity compared with standard of care agents, whereas toxicology analysis in rodents and non-rodent animal models revealed a favorable toxicity profile. The overexpression of EphA2 in a wide range of tumors, the high tumor specificity of MM-310 through the enhanced permeability and retention effect, and the EphA2 targeting support the investigation of MM-310 for potential clinical utility. Methods: This is a first-in-human, non-randomized, open-label Phase 1 study of MM-310 in patients with relapsed or refractory solid tumors. The clinical trial is divided into 3 parts. In the ongoing first part, MM-310 is assessed as a monotherapy, administered every 3 weeks at increasing dose levels (dose escalation), in patients with metastatic solid tumors, including urothelial carcinoma, gastric carcinoma, squamous cell carcinoma of the head and neck, ovarian cancer, pancreatic ductal adenocarcinoma, prostate adenocarcinoma, non-small cell lung cancer, small cell lung cancer, triple negative breast cancer, endometrial carcinoma and soft tissue sarcoma. The primary objective is to determine the maximum tolerated dose (MTD) of MM-310 monotherapy. Secondary endpoints include: characterization of adverse event profile, determination of pharmacokinetics and immunogenicity parameters, and assessment of preliminary activity of MM-310 monotherapy. In the dose-finding phase, the study uses a modified toxicity probability interval approach (mTPI) to determine the MTD of MM-310. After an MTD of monotherapy is established, an expansion cohort, and tolerability of MM-310 in combination with other therapies will be assessed. Enrollment was initiated in March 2017. Five sites in the United States are open for enrollment. Clinical trial information: NCT03076372.
Burden of Merkel cell carcinoma: A targeted literature review.
Authors: Siva Narayanan, Smeet Gala
Journal: Journal of Clinical Oncology (2017)

e21073 Background: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer characterized by high incidence of local recurrences, regional nodal metastases, distant metastases, and high mortality rates. It has no approved drug therapies and limited treatment options, especially to manage the metastatic disease. Our objective was to conduct a comprehensive review of MCC disease burden. Methods: We conducted a targeted literature review of studies published from 2010 to 2016 to assess epidemiology, patient burden, and unmet needs associated with MCC. An article was retrieved for full review if the abstract met each of the following criteria: reported incidence, natural morbidity or mortality of MCC; derived from a peer-reviewed journal; and reported in English-language published since January 2010. Results: The incidence of MCC (per 100,000 persons per year) is reported highest in Australia (0.82-1.60), followed by the US (0.6), Netherlands (0.35), Sweden (0.18-0.33), Finland (0.24-0.25), Spain (0.28), Denmark (0.22), South East Scotland (0.133), France (0.13). Inadequate data available from countries like Canada, UK, Germany and most part of Asia-Pacific. Typically, stage I-II MCC is observed in approximately 60% - 75% patients, stage III in 10% - 30% patients, and stage IV (metastatic) in 2% - 16% patients. The 5-year and 10-year survival is 0% - 68%, and 21% - 65% respectively, based on factors such as disease stage and gender. Although less than 20% patients progress to advanced metastatic stage IV MCC, they experience the highest unmet need due to lack of effective therapeutic options. Data on economic burden and humanistic burden (e.g., impact on patient quality of life) is not available. Conclusions: Epidemiological review indicates an increasing incidence of MCC; however, available estimates are at least 5 years old. Epidemiological data as well as data on clinical, economic and humanistic burden of MCC is lacking from several parts of the world. Further research is warranted to adequately quantify the burden-of-illness of MCC and assess comparative effectiveness of evolving treatment options to better inform patients, prescribers and payer organizations concerning optimal cost-effective modalities of disease management.
Phase II study of autophagy inhibition with hydroxychloroquine (HCQ) and preoperative (preop) short course chemoradiation (SCRT) followed by early surgery for resectable ductal adenocarcinoma of the head of pancreas (PDAC).
Authors: Theodore S. Hong, Jennifer Yon-Li Wo, Wenqing Jiang, Beow Y. Yeap, Jeffrey W. Clark, David P. Ryan, Lawrence Scott Blaszkowsky, Lorraine C. Drapek, Harvey J. Mamon, Janet E. Murphy, Jason Edward Faris, Eunice Lee Kwak, Jill N. Allen, Andrew X. Zhu, Lipika Goyal, Keith D Lillemoe, Cristina Ferrone, Thomas F. DeLaney, Carlos Fernandez-del Castillo, Alec Kimmelman
Journal: Journal of Clinical Oncology (2017)

4118 Background: PDAC is highly dependent on autophagy, a metabolic process that renders cancer cells resistant to cytotoxic therapies. HCQ is an inhibitor of autophagy, and has preclinical activity in PDAC. We evaluate the efficacy of concurrent and adjuvant HCQ with preop SCRT and adjuvant chemotherapy in early, resectable PDAC. Methods: Pts with radiographically resectable, biopsy-proven PDAC of the head were enrolled from 12/2011-9/2016 on this IRB-approved, NCI-sponsored clinical trial (NCT01494155). Eligibility included no involvement of SMA or celiac artery on CT; adequate renal, hepatic and hematopoetic function; and ECOG PS 0/1. SCRT was 5 Gy x 5 with protons or 3 Gy x 10 with photons concurrent with Cape 825 mg/m2 BID wk 1 and 2 M-F. HCQ was started at 400 mg po BID 1 wk prior to radiation through SCRT until the day of surgery. Surgery was performed 1-3 wks after completion of SCRT. Pts were recommended to receive 6 mo of gemcitabine-based chemotherapy after surgery. Pts resumed HCQ after discharge from surgery and continued until progression. Follow-up was performed every 3 months with CT scanning every 6 mo. Sample size of 50 to evaluate an increase of 2-year PFS from 30% to 45%. Results: 50 pts were enrolled on study and all are evaluable for this analysis. Median age- 69 (range 54-86); pre-treatment CA19-9 median 69.5 U/mL ( &lt; 1-10235), female- 24 pts (48%). Gr 3 toxicity was noted in 2 (4%) pts (nausea-1, hyperglycemia-1). All 50 pts completed SCRT. 46 pts underwent resection. Reasons for no resections: metastatic disease-2, toxicity-1, intercurrent illness- 1. 38 pts had R0 resection, 8 had R1 resection. 29 of 46 pts had positive nodes. 1 pt achieved pathologic complete response (CR), 2 pts had near CR . 11 pts remain on HCQ. Median follow up in 26 surviving pts is 18.3 months. mPFS is 11.7 mo, mOS 23.3 mo. OS-2 yr- 43.1%, PFS-2-yr 32.0%. Conclusions: HCQ with preop SCRT and adjuvant gemcitabine-based chemotherapy is well tolerated but did not meaningfully impact DFS. Further pathologic/correlative studies, particularly in outstanding pathologic responders and long term survivors are ongoing. Clinical trial information: NCT01494155.
4SC-202: Epigenetic modulation to pave the way for checkpoint inhibition.
Authors: Hella Kohlhof, Svetlana Hamm, Tanja Wulff, Roland Baumgartner, Daniel Vitt
Journal: Journal of Clinical Oncology (2016)

11546 Background: 4SC-202 is an orally available, small molecule clinical stage epigenetic modulator. Epigenetic modifiers are known to bear the potency to enhance response rates of checkpoint inhibitors and broaden the number of indications by combination treatment. Methods: 4SC-202 was tested in cellular assays and in a syngenic mouse model to investigate its capacity for immune modulation and combination treatment with checkpoint inhibitors. Results: Preclinical data demonstrate that 4SC-202 has immune priming potency by up-regulation of i) tumor associated antigens, ii) ligands for NK cell recognition, iii) MHC and costimulatory molecules, and iv) down-regulation of immunosuppression via the suppression of IDO and arginase in tumor cells as well as in myeloid-derived suppressor cells. In contrast to Entinostat and SAHA, 4SC-202 is not toxic for immune cells. By sparing the immune cells and enhancing the immunogenicity of tumor cells, 4SC-202 enables the immune system to attack tumor cells and provides a rationale for the combination with checkpoint inhibitors. To translate these effects from in vitro to in vivo, 4SC-202 was tested in a syngenic colon carcinoma CT26 mouse model in monotherapy and in combination with anti-PD1 antibody. 4SC-202 inhibited the growth of CT26 tumors at clinically relevant doses and therefore confirmed the relevance of the immunomodulating capacity of 4SC-202 for the anti-tumoral effect. The combination treatment with anti-PD1 antibody demonstrated that 4SC-202 is able to sensitize tumors for treatment with checkpoint inhibitors in indications where checkpoint inhibitors alone are not active. Conclusions: As demonstrated in a phase I clinical trial in 24 patients with relapsed or refractory hematological malignancies, 4SC-202 was well tolerated and objective responses (1 CR, 1 PR) and disease stabilizations were observed in several patients. 4SC-202 is an ideal combination partner for checkpoint inhibitors due to its immune priming capacity, the excellent safety profile and the oral formulation which allows convenient application and flexible dosing schedules.
TCT-689 Comparison of Transcatheter Aortic Valves: Stent and Leaflet Stresses of Sapien vs. CoreValve
Authors: Yue Xuan, Zhongjie Wang, Danny Dvir, Jian Ye, Julius Guccione, Liang Ge, Elaine Tseng
Journal: Journal of the American College of Cardiology (2018)
Does oral alpha lipoic acid prevent oxaliplatin-induced peripheral neuropathy? A randomized, double-blind, parallel-arm, placebo-controlled trial.
Authors: Maria Giuseppa Vitale, Carmela Barbato, Francesco Habetswallner, Bernardo Maria De Martino, Giorgio Bedogni, Felice Sirico, Ferdinando Riccardi, Maria Biglietto, Bruno Chiurazzi, Giacomo Cartenì
Journal: Journal of Clinical Oncology (2016)

10117 Background: Peripheral neuropathy is the most significant adverse reaction associated with the use of oxaliplatin. No treatment is presently available for the prevention of OXPNP. Alpha-lipoic acid (ALA) has well known neuroprotective properties. A potential effect of A LA on OXPNP has been suggested by two cohort studies and formally investigated by one randomized controlled trial (RCT). Unfortunately, the only available RCT has suffered from a substantial loss of patients during follow-up. Thus, it is unclear whether ALA is effective at preventing OXPNP. Methods: We performed a double-blind RCT of ALA vs. placebo (PLA) to test whether ALA can prevent OXPNP. The main outcome was the incidence of OXPNP during 6 months of treatment. We calculated that 55 patients per group were needed to detect an absolute 30% change in the incidence of OXPNP with a type 1 error rate of 0.05 and a power of 0.80 (Pearson’s two-tailed chi-squared test). Assuming a loss to follow-up of 10%, 60 patients per group were enrolled into the study. Patients were assigned to PLA or ALA using a computer-generated randomization list. Patients, care-givers and outcome assessors were blinded to treatment assignment. Both ALA and PLA were administered at the dose of 1600 mg b.i.d. The study protocol was approved by the local Ethical Committee and all patients gave written informed consent. Results: Of the 120 patients that were enrolled, 1 died, 3 had disease progression, 8 withdrew consent, 2 choose to be treated elsewhere, 2 had chemotherapy toxicity, 4 attributed side effects to the study treatment and1 was later found not be eligible for the study. The incidence of OXPNP on the remaining 99 patients (52 PLA and 47 ALA) was similar in the ALA [0.74 (95%CI 0.62 to 0.87)] and PLA group [0.67 (95%CI 0.55 to 0.80), p = 0.43]. Conclusion: ALA is not superior to PLA for the prevention of OXPNP.
Unstaged non-small cell lung cancer in the United States: Predictors and survival.
Authors: Amir Bista, Sandhya Sharma, Dipesh Uprety, Amit Khanal, Bibhusan Basnet, Binay Kumar Shah
Journal: Journal of Clinical Oncology (2016)

e18047 Background: Treatment and prognosis of non-small cell lung cancer (NSCLC) depends on the stage of the disease. Little is known about unstaged NSCLC in the United States. Methods: Surveillance Epidemiology and End Result (SEER) 18 registries (2014 submission) were used to identify NSCLC cases diagnosed from 1988 to 2012. ‘LRD SEER historic stage A’ was used for staging into localized, regional, distant or unstaged cases. Logistic regression was used to evaluate association of unstaged cases with various factors. Patients with history of prior cancer were excluded from survival analysis. 1 and 5 year relative survival (RS) was calculated using SEER stat and compared using Z test. Cox PH model was used to compare association of various factors with 5 year RS among unstaged cases. Results: Of the total 569,446 cases included in the study, 261,298 were included in survival analysis. Median age at diagnosis was 69 years. A total of 24,605 (4.1%) cases were unstaged. Age 65+ years, low median annual household income ( < $25000), single or separated/divorced/widowed, African American race, history of prior cancers and well differentiated carcinoma on histology were independent predictors of unstaged cases. Unstaged cases were comparable in males and females. When the study period was divided into cohorts of 5 years, recent year of diagnosis was an independent predictor of decrease in unstaged cases (adjusted OR of 0.674, P < 0.001). 1-year and 5- year RS were significantly worse in unstaged compared to localized and regional cases but better compared to distant cases in the whole population (1-year RS of 44.3% versus 85.2%, 65.3 and 25.1% respectively, with P < 0.0001; 5-year RS of 10.6% versus 57.4%, 28.4 and 3.9% respectively, with P < 0.0001). Among unstaged cases, age < 65 years, female gender, ‘others’ race and ‘married’ status were independent predictors of better 5- year RS. Survival was comparable for Caucasians and African Americans. Conclusions: Our study showed that 4.1% of patients with NSCLC were unstaged. There are disparities in the unstaged cases among various cohorts based on race, age, history of prior cancers and household income. Survival of unstaged NSCLC patients is worse than those with localized and regional stage.
Clinical efficacy and safety of apatinib combined with docetaxel in second-line treatment for advanced gastric cancer: A prospective study.
Authors: Mudan Yang, Jun Gao, Zhou Xu, Hongxia Lu, Wenhui Yang, Li Li, Hui Li
Journal: Journal of Clinical Oncology (2018)

e16006 Background: Antiangiogenic therapy in combination with chemotherapy has shown improved clinical benefit in advanced cancer. In third-line therapy, apatinib (a TKI against VEGFR-2) has shown good safety and efficacy for advanced gastric cancer. However, the safety and efficacy of apatinib combined with docetaxel in second-line treatment of advanced gastric cancer remains unclear. Methods: From Mar 2017 to Jan 2018, 13 patients with advanced gastric cancer after failure of first-line chemotherapy were enrolled in this study. All patients were treated by apatinib (500mg, qd) with docetaxel (60mg/m2,d1, q21d). According to the docetaxel course of treatment, study treatment was continued as a 21-day cycle. After 6 cycles, apatinib alone maintenance. Efficacy was evaluated every 2 cycle based on RECIST version 1.1. The primary endpoint was progression-free survival (PFS). The secondary endpoints were objective response rate (ORR), disease control rate (DCR) , overall survival (OS), safety and quality of life. Results: Thirteen enrolled patients baseline characteristics are shown in the table below. The partial response rate (PR), stable disease rate (SD), and progression disease rate (PD) were 23.08% (n = 3), 61.54% (n = 8) and 15.38% (n = 2), respectively. The ORR and DCR were 23.08% and 84.62%, respectively.The median progression-free survival has not researched. One gastric antral adenocarcinoma patient with multiple liver metastases who developed resistance after 6 cycles first-line of chemotherapy received 6 cycles of apatinib plus docetaxel, then had more than 9-month progression-free survival time.The observed adverse events in this study were bone marrow suppression(46.15%, n = 6), proteinuria(46.15%, n = 6), hypertension(23.08%, n = 3), fecal occult blood(23.08%, n = 3), and allof them was 2 grade or below. Clinical trial information: ChiCTR-OPC-17013834. Conclusions: In the second-line treatment for patients with advanced gastric cancer, apatinib combined with docetaxel exhibits superior activity. Moreover, the toxicities were tolerable and could be clinically managed. Baseline characteristics Range N % Age >60 8 61.54 Metastatic number ≥2 11 84.62 Clinicopathological staging IV 11 84.62
TCT-734 Comparison of Thromboresistance between Everolimus-eluting Fluoropolymer Stent and ELuNIR Ridaforolimus Eluting Coronary StentRidaforolimus-Eluting Stent in an Ex Vivo Swine Shunt Model
Authors: Hiroyuki Jinnouchi, Frank Kolodgie, Qi Cheng, Eduardo Acampado, Sho Torii, Atsushi Sakamoto, Maria Romero, Laura Perkins, Syed Hossainy, Stephen Pacetti, Renu Virmani, Aloke Finn
Journal: Journal of the American College of Cardiology (2018)