tbuckley/cabot-search huggingface dataset:
A phase 2 trial of INCB040093 alone or in combination with INCB039110 in patients (pts) with relapsed or refractory (r/r) classical Hodgkin lymphoma (cHL).
Authors: Paul M. Barr, Taimur Sher, Tycel Jovelle Phillips, Daniel Lebovic, Li Zhou, Jennifer Pulini, Matthew A. Spear, Andres Forero-Torres
Journal: Journal of Clinical Oncology (2015)

TPS8607 Background: In vitro data suggest that both the PI3K and JAK-STAT pathways contribute to tumor growth and survival in HL. Therapies that block both pathways may prove more beneficial in pts with r/r cHL, where treatment options are limited. INCB040093 is an oral PI3Kδ inhibitor and INCB039110 is an oral JAK1-selective inhibitor. Methods: This ongoing, nonrandomized, open-label trial has a planned enrollment of 122 pts (61 per treatment arm). Eligible pts are ≥ 18 years of age with r/r cHL after autologous stem cell transplant (SCT) and/or after ≥ 2 prior chemotherapy-containing regimens who are not candidates for autologous SCT; have fluorodeoxyglucose-avid disease; ECOG performance status 0 to 2; prior brentuximab vedotin (BV) treatment (or not a candidate for BV). Pts who received prior treatment with an immune checkpoint inhibitor are eligible if disease progression or relapse is confirmed with a second assessment ≥ 28 days later. Pts must have adequate ANC, platelet count, hemoglobin, total bilirubin, AST and ALT levels. Before first dose of study drug, pts must not have investigational agents within 28 days or 5 half-lives (whichever is greater); autologous SCT within 28 days or allogeneic SCT within 3 months; or radiation treatment within 3 weeks. Pts will receive INCB040093 100 mg bid monotherapy or INCB040093 100 mg bid with INCB039110 300 mg qd. Pts receiving benefit may continue on therapy until they meet treatment discontinuation criteria. Pts receiving INCB040093 monotherapy who experience disease progression or relapse on study may be eligible for crossover to combination therapy. The primary endpoint is objective response rate per the Lugano Classification (Cheson et al. J Clin Oncol 2014) determined by an independent review committee. Secondary endpoints include duration of response and progression-free survival. Overall survival is an exploratory endpoint. Final analysis is planned when all pts reach at least the Week 36 disease evaluation. Clinical trial information: EudraCT 2014-005631-13.
A pilot intervention addressing sexual dysfunction after risk-reducing oophorectomy.
Authors: Sharon Bober, Judy Garber, Christopher J Recklitis, Andrea Farkas Patenaude
Journal: Journal of Clinical Oncology (2013)

9644 Background: Women at high risk for ovarian cancer due to BRCA1 or BRCA2 mutation or family history are recommended to undergo prophylactic bilateral salpingo-oophorectomy (PBSO) after age 35 or completion of childbearing. This potentially life-saving surgery leads to premature menopause, frequently resulting in profound sexual dysfunction. We developed and piloted the first psychoeducational intervention for managing sexual dysfunction in young women after PBSO. Methods: This single-arm multi-modal pilot intervention study included a single half day session with educational modules about sexual health education, relaxation training, and cognitive behavioral therapy (CBT) skills to manage symptoms, followed by tailored telephone counseling. Self-report assessments, including the 19-item Female Sexual Function Index (FSFI) and a 10-item measure of sexual knowledge after PBSO were completed at baseline and two months post-intervention. Eligible women had PBSO for risk-reduction, current age ≤ 49, and endorsed at least one symptom of sexual dysfunction. Study endpoints include feasibility and effectiveness. Results: 36 women enrolled and completed pre- and post- assessments. Median age was 44 years (range 36-49) and median time since PBSO was 3.2 years (range 0.75-12.3). FSFI scores improved significantly from baseline to post-intervention for the desire (p = 0.003), arousal (p = 0.001), and satisfaction (p = 0.031) domains, as well as on the full scale score (p = 0.005). In addition, 60% of participants demonstrated improved knowledge scores about managing sexual dysfunction after PBSO following the intervention. Conclusions: The current intervention builds upon recent advances in CBT and sexual health education to address this much-neglected problem after PBSO. Results from this promising pilot intervention provide compelling preliminary data to move toward conducting a randomized clinical trial. Reducing post-PBSO distress, a valuable goal in its own right, may ultimately improve uptake of this potentially life-saving procedure in a high-risk population, as loss of sexual functioning is one of the reasons mutation carriers give for rejecting surgical risk-reduction.
Clinical outcome of adult acute lymphoblastic leukemia based on Philadelphia chromosome status and socioeconomic status.
Authors: Bao Duy Dao, Jennie York Law, Phat Le, Ang Gao, Chul Ahn, Kirthi Kumar, Larry Don Anderson, Robert Collins, Hsiao Ching Li, Prapti Arvind Patel, Navid Sadeghi, Madhuri Vusirikala, Harris V. K. Naina, Pier P. Scaglioni
Journal: Journal of Clinical Oncology (2015)

7083 Background: Adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL) often relapse with chemotherapy alone. Many undergo allogeneic stem cell transplant (alloSCT) in first complete remission (CR1). Use of tyrosine kinase inhibitors (TKI) with chemotherapy improves outcomes although the standard of care for Ph+ALL remains undefined. Methods: 105 consecutive adult patients with ALL were treated at UT Southwestern Medical Center and its county affiliate Parkland Hospital from 2004-2014. Associations between alloSCT, socioeconomic status, and overall survival (OS) were evaluated using Cox regression methods and Kaplan-Meier analysis. Results: 34 patients had Ph+ALL. Median age was 49 years. 26 patients received chemotherapy + TKI alone. 8 patients underwent alloSCT after initial chemotherapy + TKI. 82.4% of Ph+ALL patients achieved CR1. At median follow up of 18 months, 61.5% of Ph+ALL patients who did not undergo alloSCT were alive compared to 50.0% of patients who did. AlloSCT was not significantly associated with OS (p = 0.74). Survival was not significantly differed between Ph+ALL and Ph-ALL (p = 0.58). Impact of socioeconomic status on OS within the Ph+ALL group was limited by small sample size. Within the entire cohort of ALL patients, about half of patients had an indigent care plan and were treated at the county hospital. These patients had an OS of 15.5 months compared to 49 months among privately insured patients (p = 0.008). OS improved from 17.9 months for patients treated at the county hospital to 78 months for individuals treated at our university facility (p = 0.0052). In univariate analysis, OS was significantly associated with insurance type (HR = 2.09; 95% CI 1.20-3.64) and treating facility (HR 2.24; 95% CI 1.25-4.00). In multivariate analysis, this association was no longer significant. Conclusions: In the advent of TKI, alloSCT did not significantly influence OS in Ph+ALL patients. Administration of chemotherapy + TKI alone may be a viable alternative given the increased morbidity associated with alloSCT. Socioeconomically disadvantaged patients appear to have inferior survival, but this needs further investigation in a larger cohort.
Phase 2 Study of Venetoclax Plus Rituximab or Randomized Ven Plus Bendamustine+Rituximab (BR) Versus BR in Patients with Relapsed/Refractory Follicular Lymphoma: Interim Data
Authors: Pier Luigi Zinzani, Max S Topp, Sam LS Yuen, Chiara Rusconi, Isabelle Fleury, Barbara Pro, Giuseppe Gritti, Michael Crump, Wanling Hsu, Elizabeth A. Punnoose, James Hilger, Mehrdad Mobasher, Wolfgang Hiddermann
Journal: Blood (2016)
Association of presurgery neutrophil-to-lymphocyte ratio with survival outcomes in patients with urothelial carcinoma treated without neoadjuvant chemotherapy and with radical cystectomy.
Authors: Janet Baack Kukreja, Jason M Podolnick, Xuemei Wang, Hsiang-Chun Chen, Neema Navai, Ashish M. Kamat, Colin P.N. Dinney, Jay Bakul Shah
Journal: Journal of Clinical Oncology (2017)

324 Background: There is growing interest in finding inexpensive, easily reproducible biomarkers to predict outcomes in patients with urothelial bladder carcinoma (BC). An elevated preoperative neutrophil-to-lymphocyte Ratio (NLR) has been found to be an independent prognostic factor for decreased survival, predictive of upstaging at radical cystectomy (RC), and predictive of recurrence and progression. This study investigated the utility of the preoperative NLR predicting long-term outcomes in chemotherapy naïve patients undergoing RC for BC at a large tertiary care center. Methods: In a retrospective cohort study, 849 RC patients with BC were identified between 2000 and 2011. NLR data for these patients was obtained within 30 days prior to RC. Univariate CART analysis was used to determine an NLR cutoff point that was significantly associated with both overall survival (OS) and disease specific survival (DSS). OS and DSS were estimated using Kaplan-Meier curves. Results: The median follow-up time among survivors was 7.3 years. 597 (70%) patients died and 252 (30%) were alive at last follow. Using CART analysis, a preoperative NLR cutoff point of 3.19 was identified to have the strongest association with both OS and DSS (p &lt; 0.001). 562 (66%) patients had a preoperative NLR &lt; 3.19 and 475 (34%) had a preoperative NLR ≥ 3.19. The median OS and DSS for patients with preoperative NLR &lt; 3.19 was 5.96 years and 15.64 years, respectively. The median OS and DSS for patients with a NLR ≥ 3.19 was 4.44 years (95% CI: 3.18-4.81 years) and 8.23 years (95% CI: 5.15-11.87 years). DSS Kaplan-Meier curve was significant, p &lt; 0.001. Patients with a NLR &lt; 3.19 had a 5-year OS and DSS of 59% and 77%, respectively. RC patients with a NLR ≥ 3.19 had a 5-year OS and DSS of 43% and 56%. Conclusions: A preoperative NLR ≥ 3.19 is significantly associated with decreased OS and DSS in patients treated with RC for UC. This finding further validates NLR as a biomarker in BC prognosis. NLR can help to determine patients with a poor prognosis who may benefit from more aggressive, adjuvant therapy following RC.
Patterns of care and outcomes for young patients (age < 40) with metastatic colorectal cancer (mCRC): Findings from a population-based registry.
Authors: Sina Vatandoust, Timothy Jay Price, Rob Padbury, David Roder, Carol Beeke, Amitesh Roy, Amanda Rose Townsend, Christos Stelios Karapetis
Journal: Journal of Clinical Oncology (2014)

e17584 Background: Colorectal cancer is less common in those younger than 40. Some studies suggest that young patients (pts) with mCRC have more aggressive disease with worse outcomes. Methods: We analysed data from the South Australian Metastatic Colorectal Cancer database, a population based registry that collects data from all pts diagnosed with mCRC in the Australian state of South Australia from February 2006. We studied pts with mCRC who are younger than 40 years (y) and compared them with pts who were 40 y or older. Results: From 2,862 pts, 36 (1.3 %) were younger than 40 y (17.4 -39.7 y, median 35.7 y) and 2826 (98.7%) were 40 y or older (40 – 105.4 y, median 72.7 y). There were no significant differences in pt sex or living in metropolitan versus (vs) rural areas. Disease characteristics including synchronous vs metachronous metastases, site of primary disease (rectal vs colon), grade of the tumour, number of metastatic sites involved (2 or less vs more than 2) and frequency of KRAS mutation were not significantly different between the 2 groups. In the younger group a significantly higher proportion of pts received chemotherapy compared to the older group (80.6% vs 58.3% p=0.007). Use of combination chemotherapy was significantly higher in the younger group (69.4% vs 39.7% p<0.001). In the younger group, a higher proportion of pts had KRAS mutation analysis performed compared to the older group (38.9% vs 21.5% p = 0.005). Resection of metastases, liver ablation treatment strategies, use of radiotherapy and enrolment into clinical trials were not significantly different between the 2 groups. The median overall survival was not significantly different between the 2 groups [14.6 months (mo) in the younger group (95% confidence interval 10.1 – 22.7 mo) and 14.9 mo in the older group (95% confidence interval 14.0 – 15.7 mo); p=0.924.] Conclusions: Patient and disease characteristics were not significantly different between age < 40 y and age >= 40 y groups. There were differences in the pattern of care between the 2 groups, with chemotherapy and combination chemotherapy used more frequently in younger pts. The outcomes for youngpts with mCRC were not significantly different compared to older pts.
Ophthalmology. 2011 Dec;118(12):2343-50. doi: 10.1016/j.ophtha.2011.06.016. Epub 2011 Sep 1. Randomized, controlled trial of an educational intervention to promote spectacle use in rural China: the see well to learn well study.
Authors: Congdon N, Li L, Zhang M, Yang A, Gao Y, Griffiths S, Wu J, Sharma A, D S Lam
Journal: Ophthalmology (2011)
Germline mutations in seemingly sporadic pancreatic cancer.
Authors: Cavin Wong, Adeline Cuggia, Ayelet Borgida, Spring Holter, Anita Hall, Ashton Connor, Mohammad R Akbari, Steven Gallinger, George Zogopoulos
Journal: Journal of Clinical Oncology (2017)

312 Background: Genetic predisposition underlies approximately 10% of pancreatic cancer (PC). Germline mutations in BRCA1, BRCA2, PALB2, ATM, TP53, MLH1, MSH2, MSH6, PMS2, PRSS1, APC, BMPR1A, STK11, CDKN2A, and SMAD4 are associated with PC susceptibility. Since young onset is not a hallmark of hereditary PC, we have hypothesized that seemingly sporadic cases may carry germline mutations in these genes. Methods: To investigate the prevalence of germline mutations in these 15 genes among sporadic PC cases, we analyzed lymphocyte DNA next generation sequencing data from 296 PC cases ascertained over 1 year from two PC referral centers in Toronto and Montreal. Results: We identified 21 mutations in 5 of the 15 genes (10 in BRCA2, 2 in BRCA1, 5 in ATM, 1 in p16, 3 in PRSS1) in 19 individuals. One individual carried two BRCA2 mutations that are usually observed together, and another individual carried both a PRSS1 and ATM mutation, however, in the absence of pancreatitis, PRSS1 mutations are not known to increase risk of PC. Incidences of 1.7% and 4.1% in ATM and BRCA-1 or -2 were observed. Approximately half of these mutations (4/9 for BRCA2, 1/2 for BRCA1, and 1/1 for p16) were known founder mutations in the French Canadian, Ashkenazi Jewish, Dutch or Asian populations. Since the role of ATMin PC predisposition remains under investigation, we obtained further evidence by testing for loss of the wild-type allele in cases with available tumor tissue. We observed loss of the wild-type allele in the 2 cases tested. Interestingly, the final pathology for the resected specimen from one of these two cases favored an ampullary cancer rather than a PC diagnosis. Conclusions: Since there are screening implications for the relatives of carriers and potentially treatment considerations for patients using therapies targeting DNA repair defects, these findings suggest a role for reflex testing of incident cases for at least population-specific recurrent mutations. Our findings also suggest that ATM germline mutations may give rise to ampullary cancer, underlie 1.4% of incident PC cases and imply broader testing considerations. For patients, testing may direct therapy choices if these tumors are targetable using agents that exploit DNA repair defects.
When less is better: Safety and efficacy of combination of trastuzumab and continuous low oral dose chemotherapy (HEX) as first-line therapy for HER2-positive advanced breast cancer (ABC)—First early results from a phase II trial on behalf of Gruppo Oncologico Italia Meridionale (GOIM).
Authors: Laura Orlando, Francesco Giotta, Margherita Cinefra, Daniele Rizzi, Salvatore Pisconti, Salvatore Del Prete, Mariangela Ciccarese, Antonio Rinaldi, Paola Schiavone, Annamaria Quaranta, Palma Fedele, Angelo Nacci, Nicola Calvani, Vito Lorusso, Giuseppe Colucci, Saverio Cinieri
Journal: Journal of Clinical Oncology (2013)

618 Background: Clinical activity of the combination of chemotherapy plus trastuzumab in HER2+ ABC has been well documented. We report the first results in terms of activity and safety of the combination of trastuzumab plus metronomic capecitabine and cyclophosphamide as first line therapy in HER-2 positive ABC. Methods: Patients (pts) at first relapse or with synchronous metastasis, were treated with trastuzumab (4 mg/kg, loading dose 6 mg/kg) plus oral capecitabine (1500mg/daily) and cyclophosphamide (50 mg/daily). Primary end-point was overall response rate (ORR), secondary end-points time to progression (TTP), clinical benefit rate (CBR; PR+ CR + prolonged SD for ≥ 24 weeks) and tolerability. The optimal two-stage design was applied. Results: A total of 31 pts with measurable ABC, tumors scored as +3 positive for HER-2 or FISH +, no pretreated with chemotherapy or trastuzumab for advanced disease have been enrolled, 28 actually valuable for response and toxicity. Median age was 59 years (range 42-87), visceral metastases were present in most patients (61%). Median number of cycles was 12 (range 1-37+). The ORR was 61 % (95% CI, 41-78%), with 1 CR (3.6 %) and 16 PR (57.1%). 9 patients had prolonged SD (32%). The CBR was 82.1% (95% CI , 63%-94%). Five progressions were observed (18%). Median TTP was 7 months (range 2- 19 + months). Ten pts received more than 20 courses. Worst toxicities were grade 2 hand-foot syndrome in 4 pts, grade 2 anemia in 4 pts, grade 2 nausea in 2 pts and diarrhea grade 3 in 1 pt. Cardiac toxicity grade 2 in 1 pts. Alopecia was not reported. Conclusions: Combination of trastuzumab and low dose metronomic oral chemotherapy in HER-2 + breast cancer has shown clinical activity. The tolerability was excellent and allowed the prolonged delivery of the combination. Thus, the patients accrual is ongoing to the pre-set target of 66 patients. Clinical trial information: 2009-017083-16.
Quantitative measures of FDG PET after neoadjuvant chemotherapy to predict breast cancer patient survival.
Authors: Erin-Siobhain Ross Currin, Lisa K Dunnwald, Robert K Doot, Erin K Schubert, Brenda F Kurland, David A. Mankoff, Jennifer M. Specht
Journal: Journal of Clinical Oncology (2012)

1088 Background: In patients with locally advanced breast cancer (LABC), qualitative FDG positivity following neo-adjuvant chemotherapy (NC) has been shown to be inversely associated with survival (Emmering, Annals Oncol, 2008). We investigated quantitative measures of post-therapy FDG uptake, namely standardized uptake value (SUV) and glycolytic flux (Ki), as predictors of breast cancer survival. Methods: Forty-seven patients with LABC underwent dynamic FDG PET scans close to or at the end of NC and prior to surgical resection. Post-therapy FDG uptake at the primary tumor site was measured by mean SUV from 45-60 minutes after FDG injection, maximum SUV (SUVmax) from 50-55 minutes, and FDG glycolytic flux (Ki). Pathologic response (PR) was assessed for at the time of surgical resection. Cox proportional hazards models were used to estimate associations between log-transformed measures of post-therapy FDG uptake, PR and outcome. Results: Median SUVmax was 1.9 (0.9 – 9.2) and median Ki was 2.2 (0.02 – 47.7) mL/min/g. Median follow-up for relapse was 5.7 years with 11 events and 6.3 years for survival with 10 deaths. PR was not significant for DFS (p = .39) or OS (p= .48). Post-therapy FDG uptake measures showed a statistically significant ability to predict survival. SUVmax predicted DFS (p=0.02) and OS (p=0.01). Ki was associated with DFS (p &lt;0.01) and OS (p &lt;0.01). PET measured hazard ratios were not attenuated in multivariate analysis controlling for known prognostic markers such as primary tumor PR and nodal status. However, multivariate survival models appeared highly influenced by one patient with the shortest survival time (1.3 years) and highest SUVmax and Ki. Without this patient, Ki remained a borderline independent predictor of DFS (p= .08) and OS (p= .07), but SUVmax was no longer significant for DFS (p= .32) or OS (p=0.26). Conclusions: Our analysis suggests that quantitative measures of post-therapy FDG PET provide information beyond PR for predicting which LABC patients are at highest risk for relapse and death. This information may be useful in directing post-surgery treatment. Supported by NIH grants CA42045, CA138293, and CA148131.
Phase III open-label, randomized, multicenter study of NKTR-102 versus treatment of physician's choice (TPC) in patients (pts) with locally recurrent or metastatic breast cancer (MBC) previously treated with an anthracycline, a taxane, and capecitabine (ATC).
Authors: Edith A. Perez, Ahmad Awada, Joyce O'Shaughnessy, Hope S. Rugo, Christopher Twelves, Javier Cortes
Journal: Journal of Clinical Oncology (2012)

TPS1140^ Background: NKTR-102 is a topoisomerase I inhibitor-polymer conjugate that hydrolyzes to provide continuous exposure to SN-38. A phase 2 trial of single-agent NKTR-102 was conducted in pts with 3 rd -line MBC; 2 schedules (q14d; q21d) investigated a dose of 145 mg/m2. ORR was 29% (including 3% CR) with the prior ATC subset demonstrating an ORR of 31%. Dosing q21d was better tolerated; in this arm, median PFS and OS equaled 5.3m and 13.1m, respectively. Trial Design: Pts will be randomized 1:1 to receive single-agent NKTR-102 or TPC in an open-label, randomized, multicenter phase 3 study in pts with advanced breast cancer. Key Entry Criteria: Adult females, with ECOG 0 or 1 with adequate liver, kidney and marrow function. All pts must have received prior therapy with ATC (these drugs can be administered in the neo/adjuvant or locally advanced/metastatic setting). Prior A is not mandated if contraindicated. Prior toxicities must have resolved to ≤ Grade 1 (except sensory neuropathy ≤ Grade 2; complete resolution of prior diarrhea). Pts with brain metastases may be eligible, if lesions are stable for prior 3 weeks without steroids. Methods: Primary efficacy endpoint is OS. Secondary endpoints include: ORR by RECIST v1.1, clinical benefit rate (ORR+SD &gt; 6 months), PFS and QoL. NKTR-102 is given IV at 145 mg/m 2 over 90-min every 21 days without premedications. Pts randomized to TPC receive 1 of the following: eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel or nab-paclitaxel (the agent must be available at the treating institution). Pts are stratified by region, prior eribulin and receptor status (TNBC, Her2+ or Other). Target Accrual: ~840 pts will be required for sufficient events to occur in the planned follow-up time; OS will be compared using a two-sided log-rank test; 1 interim analysis will occur when 50% of the deaths are reported. PK sampling is performed in a subset of pts. CTCs (isolated by Apocell ApoStream technology) are serially assessed for potential predictive markers of response and toxicity. Enrollment is expected to remain open until late 2013.