tbuckley/cabot-search huggingface dataset:
Molecular analysis for therapy choice (MATCH) arm W: Phase II study of AZD4547 in patients with tumors with aberrations in the FGFR pathway.
Authors: Young Kwang Chae, Christos Vaklavas, Heather H. Cheng, Fangxin Hong, Lyndsay Harris, Edith P. Mitchell, James A. Zwiebel, Lisa McShane, Robert James Gray, Shuli Li, S. Percy Ivy, Sherry Singer Ansher, Stanley R. Hamilton, Paul M. Williams, James V. Tricoli, Carlos L. Arteaga, Barbara A. Conley, Peter J. O'Dwyer, Alice P. Chen, Keith Flaherty
Journal: Journal of Clinical Oncology (2018)

2503 Background: MATCH is a histology-agnostic signal finding trial targeting pathways in cancer. AZD4547 is a selective inhibitor of the fibroblast growth factor receptor (FGFR) 1-3 kinases. Methods: Patients (Pts) were screened by NGS for FGFR aberrations including amplification (≥7x), mutation, and fusion. 70/5558 (1.3%) of pts who underwent successful NGS evaluation were assigned to arm W. 52/689 (7.5%) of total pts enrolled in all treatment arms were in arm W (July 2016 to June 2017). 50 pts received treatment with AZD4547 80mg PO twice a day until progression of disease (PD) or drug intolerance. Results: 39/50 (78%) were female, 45/50 (90%) were Caucasian with a median age of 62 years (range: 22-80). 25/50 pts (50%) had received more than three prior lines of treatment. The most common histologies were breast (n = 16), urothelial (n = 7), and endometrial cancer (n = 4). Pts were divided into three groups: amplification (Amp) (n = 21), single nucleotide variant (SNV) (n = 20), or fusion (n = 9). Best confirmed response for the three groups are shown in the table below. Of 41 evaluable pts, the objective response rate was 5% (all partial response, PR), 51% stable disease (SD), and 44% PD. All pts with PR had tumors harboring FGFR fusions; one with urothelial transitional cell carcinoma (FGFR3-TACC3 F17T8) and the other with squamous cell carcinoma of cervix (FGFR3-TACC3 F17T11). Six cases [2 PR and 4 SD (2 SNV, 1 Amp, 1 fusion)] out of 41 achieved a duration of response greater than 24 weeks (disease control rate, 15%). The 6-month progression-free survival rate is 17% (90% CI: 8.6-34%): Amp 15% (90% CI: 4-58%), SNV 8% (90% CI: 2-38%), and fusion 42% (90% CI: 19-94%). Of 49 pts evaluable for adverse events (AEs), 39 experienced any AEs (80%) with 19 having grade 3/4 AEs (49%). Common AEs were fatigue, anorexia, dry mouth, nausea/vomiting, diarrhea, constipation, oral mucositis, anemia and liver function tests abnormality. Conclusions: AZD4547 demonstrated modest activity across various solid tumors with aberrations in FGFR pathway with acceptable toxicities. Further trials are warranted in tumors harboring FGFR fusions. Clinical trial information: NCT02465060. Amp SNV Fusion Total PR 0 0 2 2 SD 10 6 5 21 PD 7 9 2 18 Not Evaluable 4 5 0 9 Total 21 20 9 50
ARASENS phase 3 trial of ODM-201 in men with metastatic hormone-sensitive prostate cancer (mHSPC).
Authors: Matthew Raymond Smith, Fred Saad, Maha Hussain, Cora N. Sternberg, Karim Fizazi, E. David Crawford, Karin Sayuri Yamada, Christian Kappeler, Iris Kuss, Bertrand F. Tombal
Journal: Journal of Clinical Oncology (2017)

TPS5092 Background: Androgen deprivation therapy (ADT) ± docetaxel is recommended first-line therapy for mHSPC, but most patients progress to castration-resistant PC (CRPC). BAY-1841788 (ODM-201) is an investigational oral androgen receptor (AR) antagonist that has a unique chemical structure designed to block the growth of cancer cells through binding to the AR with high affinity and inhibiting the receptor function. In preclinical studies, ODM-201 and its main circulating metabolite are active also in known AR mutants (eg, W742L, F877L), and have been found to have negligible blood-brain barrier penetration. In the phase 1 ARAFOR and phase 1/2 ARADES trials, ODM-201 had antitumor activity and was well tolerated in men with mCRPC (Massard et al. Eur Urol. 2016;69:834‒840; Fizazi et al. Lancet Oncol. 2014;15:975‒985). Given this promising activity in mCRPC, the ARASENS trial is evaluating ODM-201 plus standard ADT + docetaxel in men with metastatic disease (mHSPC). Methods: This international, randomized, double-blind, placebo-controlled, phase 3 trial (NCT02799602) is being conducted in 23 countries. ~1300 men with newly diagnosed mHSPC will be randomized 1:1 to either ODM-201 600 mg twice daily (2×300 mg tablets) orally with food or placebo, both with ADT + docetaxel (6 cycles after randomization), and stratified by extent of disease and alkaline phosphatase levels. Key inclusion criteria are histologically or cytologically confirmed PC with documented metastases, started ADT ± first-generation anti-androgen therapy ≤12 weeks before randomization, and Eastern Cooperative Oncology Group performance status 0 or 1. The primary objective is to show superior overall survival with ODM-201 vs placebo, both with ADT + docetaxel. Secondary end points include time to CRPC, initiation of subsequent anticancer therapy, symptomatic skeletal event-free survival (SSE-FS), time to first SSE, initiation of opioid use, pain progression, and worsening of physical symptoms, all measured at 12-week intervals. Safety will be assessed by adverse events. The trial is open for enrollment; first patient first visit was in November 2016 and &gt; 10 sites are open for recruitment and enrolling patients. Clinical trial information: NCT02799602.
Abstract 19115: Genome-Wide Association Study and Replication Identifies a Novel Genetic Locus for Aortic Stenosis
Authors: Hao Yu Chen, Benjamin J Cairns, Line Dufresne, Hannah Burr, Athithan Ambikkumar, Aeron Small, Albert Nguyen, Johan Ljungberg, Ulf Näslund, Bengt Johansson, Jian Rong, Dilrini K Ranatunga, Rachel A Whitmer, Vasan S Ramachandran, Vilmundur Gudnason, Christopher J O'Donnell, Jerome I Rotter, Wendy Post, Stefan Söderberg, Robert Clarke, J. Gustav Smith, Daniel J Rader, Mark Lathrop, James C Engert, George Thanassoulis
Journal: Circulation (2017)

Introduction: Aortic stenosis (AS) is the most prevalent valvular heart disease in developed countries. Currently, the LPA locus is the only genome-wide significant susceptibility locus for AS. The...
Multi-modality therapy for stage IIIa N2 non-small cell lung cancer: Does the answer lie in the components?
Authors: Jonathan David Spicer, Jitesh B. Shewale, Matthew Joseph Bott, David Randolph Jones, Ara A. Vaporciyan, Gail Elizabeth Darling, Stephen Swisher, Boris Sepesi
Journal: Journal of Clinical Oncology (2017)

8537 Background: Neoadjuvant chemoradiation prior to surgery offers excellent locoregional control, while neoadjuvant chemotherapy I meant to offer improved systemic therapy in stage IIIA N2 non-small cell lung cancer (NSCLC). Data are lacking to select the optimal regimen. We compared oncologic outcomes for stage IIIA N2 NSCLC utilizing granular data from three experienced lung cancer treatment centers. Methods: This collaborative retrospective study unites 3 major thoracic centers with differing approaches to IIIA N2 NSCLC. Patients undergoing surgical resection post-neoadjuvant chemotherapy (CxT) or concurrent chemoradiation (CxRT) were included. Primary outcomes were overall and disease- free survival (OS and DFS). Results: Demographic data and outcome data are in Table 1. There were no differences in 5-year OS (CxT 40% vs CxRT 42%, p=0.265) nor in DFS (CxT 30% vs 31%, p=0.275). Recurrence rates (CxT47%vsCxRT48%,p=0.799) and patterns were identical (Local: CxT 10% vs CxRT 8%; and Distant: CxT 30%vsCxRT29%,p=0.764). There was no difference in peri-operative mortality. To address potential bias from differing staging strategies, we excluded patients without invasive mediastinal staging and there were still no differences in OS (CxT 40% vs CxRT 42%, p=0.364) and DFS (CxT 30% vs CxRT 31%, p=0.332) Multivariable analysis identified pnemonectomy (HR1.66,p&lt;0.001) and ypN2 (HR1.84,p&lt;0.001) to be associated with overall survival. Conclusions: Both treatment strategies produce equivalent and better than expected outcomes compared to historical controls for IIIA N2 NSCLC. [Table: see text]
Rural Cancer Awareness and Early Detection Initiative (RCAEDI).
Authors: Darshit Arunbhai Thaker, Parth D Thaker
Journal: Journal of Clinical Oncology (2018)

e18639 Background: Early detection and awareness of cancer is pivotal for developing countries to improve the overall outcome. Cancer incidence and mortality is steadily increasing in India, with > 70% of the cases are diagnosed in advanced stages. Most common cancers oral, breast and cervical cancer, are detectable early via regular screening. Government programs for screening are not effective enough. Most cancer institutions are located in urban parts of the country and focused on treatment rather than screening and prevention. There is minimal focus to the rural areas. Frequent opportunistic screening is one effective way to intervene. Methods: Cancer awareness and early detection camps were organised at three rural sites every four months. Thorough oral examination and onsite biopsy of suspicious lesions were done for all attendees. Thorough breast examination and pap smear were done for all female attendees. Females with suspicious breast exam, females over 50, previous history of breast cancer and family history of breast cancer had mammogram as well. Cancer awareness video clips and poster presentation was organised on site to educate rural population about risk factors and early signs of various cancers. Results: Three camps done so far at three different rural sites. Total 640 people from the rural community attended the camps. Patients already diagnosed with cancer and currently under treatment were excluded from data collection. Total thirty six (5.6%) suspicious cases were identified and further follow up was arranged at low cost not-for-profit regional cancer centre. Twenty nine cases (4.5%) were found having confirmed malignancy in early stages. Eleven cases had breast cancer (37.9%), six cervical cancer cases (20.6%), twelve oral cancer cases (41.3%) were diagnosed and treated. Two cases of advanced cancer were also diagnosed in the camp. Conclusions: Opportunistic population based screening of oral, breast and cervical cancers is successful way of timely diagnosis and management. It can improve the overall outcome of cancer in India. Future vision is to organise such camps every month at different clusters of villages and cover larger population. Same location should be repeated every two years.
The impact of primary care access on mortality in lung cancer patients from Bronx, New York.
Authors: Christopher Su, Vincent Chau, Balazs Halmos, Chirag D Shah, Rasim A. Gucalp, Stuart H. Packer, Kevin Wilson, Roman Perez-Soler, Haiying Cheng
Journal: Journal of Clinical Oncology (2018)

e18614 Background: Racial and ethnic disparities in cancer care are well described. Lack of access to primary care physicians (PCPs) may be an important contributor to disparities attributed to race and ethnicity. This study examined the effects of primary care access on mortality in lung cancer (LC) patients (pts) in an underserved community. Methods: Medical records of all pts newly-diagnosed with primary lung cancer between 2012-2016 at a NCI-designated cancer center in the Bronx were reviewed. Demographic data and PCP status were collected. Addresses were correlated with the Health Resources and Services Administration (HRSA) database to identify residences located in primary care shortage areas (PCSAs). Survival data from time of first imaging to death or the end of follow-up on January 1, 2018 were recorded. Data analysis was performed via univariate methods. Survival analysis was performed using Kaplan-Meier and Cox hazards modeling. Results: Among 1062 pts, 874 (82%) resided in a PCSA, 314 (30%) were Hispanic (H), and 445 (42%) were African-American (AA). Hs and AAs were more likely to reside in PCSAs (p = 0.0002 and p = 0.0008) and in ZIP codes with lower income (both p < 0.0001). Hs and AAs were more likely to depend on public insurance (p = 0.01 and p = 0.02). Pts who live in PCSAs presented at higher stages at the time of diagnosis (p = 0.03) and were diagnosed predominantly in inpatient settings with acute symptoms (p < 0.0001) rather than outpatient clinics (p = 0.0002). In the overall population, PCSA residence (mean: 24 vs. 30 months, p = 0.03, HR = 1.27) and no established PCP (mean: 22 vs. 28 months, p < 0.0001, HR = 1.50) were associated with increased all-cause mortality. In Cox modeling adjusting for stage at diagnosis and PCSA residence, lack of established PCP still predicts increased mortality (p = 0.03, HR = 1.20). Conclusions: Among new pts with LC, lack of established PCP is associated with increased mortality. Hs and AAs are more likely to reside in PCSAs, suggesting the link between increased mortality and race/ethnicity may be mediated by lack of access to primary care. Our results demonstrate that effective health policy efforts to reduce lung cancer mortality must include approaches to improve access to primary care.
Survival and safety in patients with advanced ovarian cancer undergoing aggressive primary and interval debulking surgery.
Authors: Shinichi Tate, Kyoko Nishikimi, Ayumu Matsuoka, Makio Shozu
Journal: Journal of Clinical Oncology (2018)

e17525 Background: Although aggressive surgery in patients with advanced ovarian cancer is necessary to achieve complete resection, there is a higher risk for perioperative complications during more complex surgeries. Therefore, we performed aggressive surgery at interval debulking surgery (IDS) after neoadjuvant chemotherapy (NACT) as well as primary debulking surgery (PDS). We report on the safety and survival of patients with advanced ovarian cancer undergoing PDS and IDS. Methods: Overall, 222 consecutive patients with epithelial ovarian cancer, fallopian tubal cancer, or peritoneal cancer diagnosed surgically at our institution between January 2008 and December 2016 were enrolled. All participants had stage III/IV cancer. PDS or NACT/IDS was determined based on tumor burden, ascites, and performance status. In the IDS group, we performed exploratory laparotomy and marked the margins of the implant disease ( > 1 cm in diameter) with 3-0 black silk and the marked lesions were removed at IDS, even if the disease not seen. We used the surgical complexity score (SCS). Results: The median patient age was 61 years, and 147 (66%) patients had Stage III disease, while 75 (33%) had Stage IV disease. Serous carcinoma accounted for 70% of all cases. Overall, 97 (43%) patients underwent PDS. Of the 125 patients who underwent NACT, 106 patients underwent IDS (NACT/IDS), while 19 patients could not undergo IDS due to disease progression. Median SCS was 10. SCS for patients who underwent NACT/IDS was significantly higher than that for those who underwent PDS (PDS; 8, IDS; 13, p < 0.001). Overall, 181 (82%) patients achieved complete resection, 19 underwent optimal (residual tumor < 1 cm), and 22, suboptimal. Major perioperative complications occurred in 9 patients: grade IIIb (n = 7), grade IV (n = 1), and grade V (n = 1). The median follow-up time was 33 months (IQR: 19.4-55.8 months). The median progression-free survival and overall survival for the whole cohort were 27 and 72 months, respectively. Conclusions: NACT/IDS reduces perioperative complications without reducing surgical complexity. We are going to perform aggressive surgery during IDS to overcome the biological behavior.
A phase 1, open-label, dose-escalation, multicenter study to evaluate the tolerability, safety, pharmacokinetics, and activity of ADCT-301 in patients with relapsed or refractory CD25-positive acute myeloid leukemia.
Authors: Martin S. Tallman, Jay Marshall Feingold, Alexander I. Spira, David Rizzieri, Ehab L. Atallah, Wendy Stock, Nitin Jain, Roland B. Walter, Ki Y. Chung
Journal: Journal of Clinical Oncology (2016)

TPS7071 Background: In normal human tissue, CD25 expression is mainly limited to activated T- and B-cells. Expression of CD25 by AML blast cells is associated with adverse outcomes, including induction failure, relapse, and shortened overall survival. ADCT-301 is an antibody drug conjugate (ADC), composed of the human monoclonal antibody, HuMax-TAC, directed against CD25, and conjugated through a cleavable linker to SG3199, a pyrrolobenzodiazepine (PBD) dimer cytotoxin. The PBD dimers are highly efficient anticancer drugs that bind in the minor groove of DNA and form highly cytotoxic DNA interstrand cross-links. After binding to the cell surface and internalization, ADCT-301 is transported to the lysosomes, where the protease sensitive linker is cleaved and free PBD dimers are released inside the target cell. Methods: This is a Phase 1, open-label, dose escalation (Part 1) and expansion (Part 2) study of the safety and tolerability of ADCT-301, used as monotherapy, in patients with relapsed or refractory CD25-positive AML. The study will determine the maximum tolerated dose (MTD), as well as evaluate the preliminary activity, PK, and pharmacodynamics (PD) of ADCT-301. In Part 1, patients will be assigned to treatment according to a 3+3 dose-escalation design and oversight by a Dose Escalation Steering Committee (DESC). In Part 2, all patients will be assigned to the dose level of ADCT-301 identified in Part 1. Clinical trial information: NCT02588092.
The Learning Curve for Robot-assisted Partial Nephrectomy: Impact of Surgical Experience on Perioperative Outcomes
Authors: Alessandro Larcher, Fabio Muttin, Benoit Peyronnet, Geert De Naeyer, Zine-Eddine Khene, Paolo Dell’Oglio, Cristina Ferreiro, Peter Schatteman, Umberto Capitanio, Frederiek D’Hondt, Francesco Montorsi, Karim Bensalah, Alexandre Mottrie
Journal: European Urology (2018)
ZUMA-4: A phase 1/2 multicenter study evaluating the safety and efficacy of KTE-C19 (anti-CD19 CAR T cells) in pediatric and adolescent subjects with relapsed/refractory B-precursor acute lymphoblastic leukemia (r/r ALL).
Authors: Alan S. Wayne, Leonard S. Sender, Daniel Warnell Lee, Rupert Handgretinger, Patrick A. Brown, Yizhou Jiang, Lynn Navale, Shanna Stout, Jeff Aycock, Jeffrey S. Wiezorek, Rajul K. Jain
Journal: Journal of Clinical Oncology (2016)

TPS7075 Background: ALL is the most common childhood malignancy. While approximately 80% of patients achieve durable complete remissions (CR) following initial treatment, the 20% of patients with relapsed or refractory disease have poor outcomes and require effective new therapies. An ongoing study at the National Cancer Institute (NCI) using anti-CD19 CAR T cells with CD28/CD3-zeta signaling domains showed complete remissions in 14 of 20 pediatric subjects with r/r ALL. (NCT01593696; Lee, Lancet 2015). KTE-C19 is an autologous, anti-CD-19 CAR T cell therapy that utilizes the same construct investigated in the NCI studies, manufactured in a streamlined 6 - 8 day process. Here we describe a phase 1/2 study evaluating KTE-C19 in pediatric and adolescent patients with r/r ALL. Methods: Subjects with r/r ALL will be treated with fixed dose fludarabine and cyclophosphamide conditioning chemotherapy followed by a single infusion of KTE-C19 at a target dose of 2 x 106 anti-CD19 CAR T cells/kg. Phase 1 will enroll 3-12 subjects, and the primary objective is to evaluate the safety of KTE-C19. In phase 2, approximately 75 subjects will be enrolled. The primary objective is to evaluate the efficacy of KTE-C19 assessed by overall CR rate (CR + CR with partial hematologic recovery, CRh). Key secondary objectives include describing duration of response, minimal residual disease-free rate, rate of allogenic stem cell transplant, OS, and safety. Exploratory objectives include pharmacodynamics and predictive biomarker analyses. Eligible subjects will have ≥ 5% marrow blasts, and be 2-21 years old. Subjects with Ph+ ALL and with low burden central nervous system (CNS) disease are eligible. Subjects with Burkitt’s leukemia/lymphoma or chronic myelogenous leukemia lymphoid blast crisis, extramedullary disease only, active GVHD, or clinically significant infection are not eligible. The trial is planned at approximately 25 sites in the US and EU. The study opened to accrual on December 7, 2015. Clinical trial information: NCT02625480.
National Cancer Data Base analysis of proton versus photon radiotherapy in non-small cell lung cancer (NSCLC).
Authors: Madhusmita Behera, Kelli A OConnell, Yuan Liu, Theresa Wicklin Gillespie, Rathi Narayana Pillai, Pretesh Patel, Charles B. Simone, Cliff Grant Robinson, Taofeek Kunle Owonikoko, Chandra Prakash Belani, Fadlo Raja Khuri, Walter John Curran, Suresh S. Ramalingam, Kristin Ann Higgins
Journal: Journal of Clinical Oncology (2016)

8501 Background: Dosimetric studies in lung cancer reveal substantial advantages for proton (PRT) versus photon (PHT) radiotherapy in sparing of normal tissues such as heart and lung, with recent randomized data (RTOG 0617) suggesting that excess radiation dose to these structures may directly reduce overall survival (OS). Whether PRT may improve OS in NSCLC patients is unknown. We analyzed outcomes and predictors associated with PRT for NSCLC in the National Cancer Data Base (NCDB). Methods: The NCDB was queried to capture patients (pts) with stage I-IV NSCLC treated with thoracic radiation from 2004-2012. The univariate (UV) association of OS was assessed using Cox proportional hazards models and log-rank tests. A multivariable (MV) Cox proportional hazard model and Kaplan-Meier (KM) analyses were performed to compare PRT vs. PHT. A logistic regression model was used to determine the predictors associated with PRT. Propensity score matching method was also implemented to reduce treatment selection bias. All analyses were performed using SAS Version 9.3. Results: A total of 140,383 pts (PHT-140,035; PRT- 348) were included in the analysis. Pt characteristics: median age 68 yrs; males 57%; stage II/III - 59%, whites 85%, academic centers 27%, metro locations 78%. Pts were less likely to receive PRT in community (OR 0.2, p < 0.001) or comprehensive community centers (OR 0.32, p < 0.001) compared to academic centers. On MV analysis, receipt of PHT was associated with an increased risk of death relative to PRT (HR 1.46, p < 0.001). For pts with stage II and III disease, 5 year OS was 15% in PHT (n = 78428) vs. 22.3% in PRT (n = 193); p = 0.01. On MV and UV analysis, stage II and III pts treated with PHT were associated with worse survival compared to PRT (HR 1.19; p value = 0.06 and HR 1.23; p = 0.02). On propensity matched analysis, PRT was associated with better 5 year OS compared to PHT (23% vs. 14%; p = 0.024). Conclusions: Thoracic radiation with protons is associated with better survival rates in stage II/III NSCLC pts in this retrospective database analysis. There is an active phase III randomized trial (NRG Oncology 1308) evaluating if chemotherapy and PRT for stage III NSCLC patients improves survival over chemotherapy and PHT.