tbuckley/cabot-search huggingface dataset:
Randomized phase III trial of gemcitabine/carboplatin with or without iniparib (BSI-201) in patients with previously untreated stage IV squamous non-small cell lung cancer (NSCLC).
Authors: D. R. Spigel, P. G. Harper, J. D. Hainsworth, F. De Marinis, F. F. Kabbinavar, E. S. Kim, T. J. Lynch, R. Rosell, F. A. Shepherd, M. A. Socinski, A. Vergnenegre
Journal: Journal of Clinical Oncology (2011)

TPS220 Background: Recent advances in the treatment of NSCLC, including bevacizumab and pemetrexed, have been limited to patients with non-squamous cancers because of concerns of safety and efficacy. Poly (ADP-ribose) polymerase-1 (PARP1) is a critical DNA repair enzyme, and is significantly upregulated at the mRNA level in multiple cancer types, including squamous cell lung cancer. Iniparib is a novel agent with PARP1 inhibitory activity and has demonstrated synergistic activity with gemcitabine and carboplatin in preclinical studies. This phase III study will compare the results of treatment with the gemcitabine/carboplatin doublet alone or in combination with iniparib. The primary endpoint is overall survival. Methods: Trial Design: Patients are randomized 1:1 to Arm A (with iniparib) or Arm B (without iniparib). All patients receive gemcitabine 1000 mg/m2 IV days 1 and 8, and carboplatin AUC=5 IV on day 1 of each 21-day cycle. Arm A patients also receive iniparib 5.6 mg/kg IV on days 1, 4, 8, and 11. All patients are assessed for response per RECIST version 1.1 every 6 weeks. While 6 treatment cycles are planned, patients without evidence of progression or other reason for discontinuation may remain on treatment beyond 6 cycles. Accrual of 825 patients provides 90% power to detect an improvement in survival from 8 months (anticipated with gemcitabine/carboplatin) to 10.7 months. Eligibility: Patients with newly diagnosed stage IV (M1a and M1b) squamous NSCLC with ECOG PS 0-1 are eligible, including those with disseminated metastases or malignant pleural or pericardial effusions. Patients may have had carboplatin in the adjuvant setting for early stage disease, but prior treatment with gemcitabine or iniparib is not allowed. Additional exclusion criteria include: history of recent cardiac disease, untreated brain metastases, and treatment for early-stage lung cancer within 12 months of study entry. There are currently 167 patients enrolled with a total of 825 planned in this international multi-center trial.
Cabazitaxel for metastatic castration-resistant prostate cancer (mCRPC): Final quality-of-life (QOL) results with safety data from the United Kingdom (UK) Early Access Programme (EAP) (NCT01254279).
Authors: Amit Bahl, Susan Masson, Zafar I. Malik, Alison J. Birtle, Santhanam Sundar, Robert J. Jones, Nicholas David James, Malcolm David Mason, David Bottomley, Anna Lydon, Simon Chowdhury, James Wylie, Johann Sebastian De Bono
Journal: Journal of Clinical Oncology (2013)

91 Background: Several drugs can now improve survival in mCRPC after docetaxel, including cabazitaxel, a next generation taxane. TROPIC (NCT00417079) showed an overall survival benefit of 2.4 months for cabazitaxel compared with mitoxantrone for mCRPC. The UK EAP provided patients access to cabazitaxel; detailed QOL and safety data were recorded. Interim analysis suggested improvements in QOL, particularly pain scores and a good safety profile. We report final QOL and updated safety data. Methods: 108 patients recruited at 12 centres received cabazitaxel 25mg/m 2 intravenously every 3 weeks with oral prednisolone 10mg daily. EQ-5D questionnaires and health state visual analogue scale (VAS) were completed at baseline, at alternate cycles and at 30 days post treatment. Safety assessments followed each cycle. Results: According to EQ-5D and VAS scores, QOL was stable with an overall trend towards improvement in patients who continued treatment. Paired ‘within patient’ analyses also support this trend. Improved pain was noted more frequently than deterioration at all time points and pain scores were at least stable in 96% of patients at cycle 10. A median of 6 cycles were given. 34 patients (31%) received 10 or more cycles. Grade 3/4 adverse events were uncommon, the most frequent being fatigue (9.3%), diarrhoea (2.8%) and neutropenic sepsis (1.9%). 85% received prophylactic granulocyte colony stimulating factor. Conclusions: Almost 1/3 of patients completed 10 or more cycles in the UK EAP. QOL was stable with trends to improved EQ-5D and VAS scores. Improved or stable pain was observed in the majority of patients continuing therapy. The UK EAP provides the first data on QOL benefit with cabazitaxel in mCRPC post docetaxel and demonstrates manageable toxicity. Final safety data will be available for presentation. Clinical trial information: NCT01254279. [Table: see text]
Pro-Apoptotic Effects on CLL (Chronic Lymphocytic Leukemia) of ABT-737, a Novel Fully Synthetic Bcl-2/Bcl-XL Antagonist.
Authors: Shinichi Kitada, Edward Monosov, Sharon Chandler, Esther D. Avery, Thomas J. Kipps, Saul H. Rosenberg, John C. Reed
Journal: Blood (2004)
Evaluation of the Oncotype DX genomic prostate score for risk stratification in prostate cancer patients considered candidiates for active surveilance.
Authors: Ganesh K Kartha, Yaw Nyame, Eric A. Klein
Journal: Journal of Clinical Oncology (2014)

122 Background: With evidence showing over treatment, more patients are choosing active surveillance (AS) for intermediate or lower risk prostate cancer (CaP). Genomic profiling is offered to risk stratify patients to aid in management decision−making. This study reports risk discrepancies between National Comprehensive Cancer Network (NCCN) criteria and OncotypeDx Genomic Prostate Score (GPS) and how this influences decision−making in our CaP population. Methods: An inception cohort study was carried out on 56 patients with NCCN very low to intermediate risk CaP who were candidates for AS and underwent GPS testing on prostate biopsy specimens performed within 6mo of entry. GPS provided a score corresponding to a GPS-based risk stratification. Study endpoints: 1) distribution of GPS risk groups within each NCCN risk category; 2) frequency of change to lower or higher risk based on GPS; 3) effect of GPS on physician recommendations and patient choice on disease management. Results: 52/56 patients had sufficient carcinoma on biopsy for a GPS analysis. GPS reassigned risk in 23% (12/52) of patients, with 10 going from NCCN low risk to GPS very low risk and 2 assigned to a higher GPS risk profile (Table). AS was recommended in 19 patients with GPS very low risk group and 8 patients in the GPS-defined low risk group. Physicians recommended treatment to 7 patients with GPS intermediate risk. Patient choice was congruent with physician recommendation in all cases. No patients chose AS when assigned to a higher risk category. All 10 patients reassigned to a lower risk category chose AS. Conclusions: In this CaP cohort, assessment by GPS changed risk stratification in 23% of patients. Moving to a different risk category changed physician recommendation and patient choice in the corresponding direction (to surveillance or therapy) in all cases. More study and larger sample size are needed to fully assess the effect of GPS on clinical decision making. [Table: see text]
Obesity and Body Weight Independently Predict Relapse and Survival in Preadolescents and Teenagers with Acute Lymphoblastic Leukemia (ALL). A Retrospective Analysis of Five Children Cancer Group (CCG) Studies.
Authors: Anna Butturini, Fred Dorey, Paul Gaynon, Cecilia Fu, Janet Franklin, Stuart Siegel, Nancy Sacks, Nita Siebel, David Henry, Paul Rogers, Beverly Lange, Harland Sather, Michael Trigg, Archie Bleyer
Journal: Blood (2004)
GMI-1070: A Small Pan-Selectin Antagonist That Inhibits Leukocyte Adhesion and Migration in Multple Disease Models In Vivo.
Authors: John L. Magnani, Arun Sarkar, Yonhong Li, Scarlett Goon, Bea Wagner, Jungshan Chang, Beat Ernst, Paul S. Frenette, John T. Patton
Journal: Blood (2007)
Outcomes of a late second autologous hematopoietic stem cell transplant compared to nontransplantation salvage therapy in relapsed multiple myeloma after upfront transplant.
Authors: J. M. Azar, S. Abdelqader, R. Abonour, A. Suvannasankha, R. Tabbey, S. Farag
Journal: Journal of Clinical Oncology (2011)

8071 Background: A second late autologous hematopoietic stem cell transplant (ASCT) has been considered as an option for patients with multiple myeloma (MM) who have relapsed after previous high-dose chemotherapy performed as part of upfront therapy. The relative benefit of a late second ASCT compared to nontransplantation salvage therapy is currently unknown. Methods: The study included 270 consecutive MM patients who relapsed after upfront ASCT, treated at Indiana University Simon Cancer Center from 1999 till 2009. 19 patients received a late second ASCT for relapsed disease. Most patients in both groups received post-relapse salvage therapy with thalidomide, lenalidomide, and bortezomib. Survival was calculated from the time of the first relapse post upfront ASCT. Univariate analysis was done to analyze the effect on overall survival of: stage, number of prior therapies (<3 vs. ≥ 3), duration of first response, age at diagnosis, hemoglobin (< 10 vs. ≥ 10), calcium (< 11 vs. ≥ 11), albumin (<3.5 vs. ≥3.5), and beta-2 microglobulin (<5.5 vs. ≥ 5.5). Results: The median duration between the first and second transplant was 40.4 months. There was no statistically significant difference between both groups in baseline characteristics (Table). The number of salvage treatments post-relapse was comparable (Table).The median survival was 6.4 years in the single ASCT group vs. 5.2 years in the second ASCT group (p = 0.8048). The 3-year survival probability was 73% for the single transplant group and 88% for the late second ASCT group. Stage was not significant in predicting survival time (p = 0.1430) nor was the number of transplants (p = 0.8048). In the univariate analysis, only the duration of first remission was found to be significant (p < 0.0001) independently from the management group. Conclusions: A late second ASCT does not seem to impact survival of patients with relapsed MM. Baseline characteristics Single ASCT Late second ASCT No of salvage treatments 2.9 (0-8) 2.6 (1-4) Duration of first remission 1.5 (0.2-4.5) 1.7 (0.4-4.4) Age 56 (25-73) 54 (38-73) Albumin 3.7 (1.7-13.8) 3.9 (3.2-4.5) Beta2 microglobulin 5.6 (0.6-27.6) 8.7 (2.2-28.4)
A phase II trial of dasatinib in patients with unresectable locally advanced or stage IV mucosal, acral, and solar melanomas: An Eastern Cooperative Oncology Group study (E2607).
Authors: Kevin Kalinsky, Sandra J. Lee, Donald P. Lawrence, A. John Iafrate, Darrell R. Borger, Bruce Jeffrey Averbook, Ahmad A. Tarhini, John M. Kirkwood
Journal: Journal of Clinical Oncology (2012)

8522 Background: Pre-clinical studies report a critical role of c-KIT mutations in mucosal, acral, and solar melanomas. Clinical trials of KIT-directed therapy with imatinib and sunitinib demonstrate activity in these subtypes. Unlike other TKIs, dasatinib inhibitory activity is seen in melanoma cell lines with the most common KIT mutation at exon 11L576P. E2607 tests the efficacy of dasatinib in treatment-naïve or previously treated patients (pts) with these unresectable subtypes. Methods: Pts receive dasatinib 70 mg PO twice daily for this two-stage phase II trial. The primary objective is response rate (RR: RECIST). Stage I was open to KIT mutated (KIT+) and wild-type (KIT-) tumors with these subtypes (n=56). Depending upon the interim analysis, stage II would pre-select for KIT+. If the overall response rate were &lt; 5%, the study would be terminated. Secondary objectives include progression-free survival (PFS), overall survival (OS), safety, and KIT mutation status. Results: Between May 2009-Dec 2010, 57 pts have been accrued to stage I. Of 54 (2 no therapy, 1 ineligible), 26 have mucosal (48%), 13 acral (24%), and 15 solar melanomas (28%). As of Jan 2012, the median f/u is 15 months (mo, range: 4-24 mo). Best responses (n=52) are 1 complete (CR: 2%), 3 partial (PR: 6%), 13 stable disease (25%), 29 progression (56%), and 6 unevaluable (11%). 51/52 have progressed (median PFS: 1.9 mo, 95% CI: 1.5-2.8) and 40/54 died (median OS: 7.4 mo, 5.7-10.8). KIT status has been assessed in 42 pts: 39 KIT- (93%) and 3 KIT+ (7%). PR is seen in 1/39 KIT-. All KIT- have died: median PFS (1.8 mo, 95% CI: 1.4-2.9) and OS (6.8 mo, 95% CI: 5.2-10.8). Of the 3 KIT+ (1 acral, 2 mucosal), 2 have died (PFS 1.4-2.5 mo, OS: 1.4-10.5 mo), and 1 refused f/u (OS: 13.3+ mo). The pt with a CR is alive at 14.4+ mo (unknown KIT status). Toxicities include 1 grade IV (elevated lipase) and grade III dyspnea (n=7), nausea (n=6), and vomiting (n=3). Conclusions: Further evaluation of dasatinib should be pursued in pts selected for KIT+ and subtype, given the lack of promising results in Kit-(&lt;5% RR). The current trial is revised to enroll only KIT+ acral, mucosal, and vulvovaginal melanomas and available via CTSU.
Assessing the value of hepatic arterial phase CT imaging in patients with breast cancer.
Authors: David Motiuk, Danny Ng
Journal: Journal of Clinical Oncology (2015)

5 Background: Hypervascular liver metastases, classically seen in melanoma and other cancers, may be best seen on a hepatic arterial phase (HAP) CT and possibly missed on the standard portal venous phase (PVP). Breast cancer sometimes produces hypervascular liver metastases, but the incidence of this is not well established. Hence, some centers perform biphasic liver CT (HAP + PVP) as standard protocol in breast cancer patients, while others do not. Our center does not include HAP in this patient population; although, it is sometimes protocolled with HAP as per radiologist preference. We sought to determine if the detection for presence or absence of liver metastases is significantly affected by the addition of HAP in breast cancer. Methods: This retrospective study was conducted using a custom search on our Picture Archiving and Communication System for all female patients who received a biphasic liver CT (HAP + PVP) from Mar 2013 - Mar 2015. Inclusion criteria included known breast cancer, liver metastases described on CT report, and follow-up imaging to confirm the finding. A total of 25 CT studies met inclusion criteria. Results: 14/25 (56%) studies demonstrated typical non-hypervascular hepatic metastases. 11/25 (44%) demonstrated hypervascular hepatic lesions. Of these latter, 4/25 (16%) represented hypervascular metastases, while 7/25 (28%) pertained to indeterminate arterial-enhancing lesions called suspicious by the reporting radiologist. Further imaging including MRI, ultrasound, and follow-up CT were recommended in these indeterminate suspicious lesions, all of which confirmed benign entities. Of the 18 studies with true hepatic metastases, the presence of metastatic disease was detectable on the PVP in 18/18 (100%, P&lt; .0001) regardless of the metastases’ hypervascular status. Conclusions: We found hypervascular metastases to be present in 22% (4/18; CI 95 [3-41%]) of breast cancer patients with true liver metastases. However, the detection for the presence of hepatic metastases was not improved with the addition of HAP. The HAP instead led to detection of more indeterminate but ultimately benign entities of no clinical significance, thus resulting in unnecessary imaging and arguably greater patient anxiety.
A quality outcomes analysis following treatment with personalized genomic cancer medicine.
Authors: Lincoln Nadauld, Bryce Perkins, Gary Stone, Heather Gilbert, Brian P. Tudor, Karen Yin Lin, James M. Ford, Derrick S. Haslem
Journal: Journal of Clinical Oncology (2014)

12 Background: Personalized genomic cancer medicine is an approach that has long shown efficacy in molecularly-defined subsets of breast and lung cancers, amongst others, but has not been employed more broadly, in part, due to limitations in testing technologies. Recent advances in genomic technologies have increasingly alleviated these constraints, thereby enabling precision cancer medicine. Data regarding the quality outcomes of patients treated with precision cancer medicine is an important next step along the path to widespread employment of this approach. Methods: We performed an IRB-approved retrospective analysis evaluating the use of targeted therapies matched to patients’ molecular aberrations as determined by genomic testing and recommended by a Molecular Tumor Board (MTB). This study assessed whether a detailed molecular profile of advanced solid malignancies including, but not limited to, the lung, gastrointestinal tract, bladder, prostate, ovary, uterus and skin, that were subsequently treated with matched targeted therapies resulted in improvements in three quality outcome measures: 1) Progression Free Survival (PFS), 2) treatment related morbidity, and 3) cost of treatment. Results: Preliminary results of the cohort analysis suggest that the costs associated with genomic targeted therapy are comparable to standard therapies; however, the costs of treatment related morbidities is significantly lower for patients receiving genomic cancer medicine compared to standard chemotherapy approaches. In line with these findings, overall treatment related morbidities are significantly reduced in the genomic cancer medicine cohort compared to a control cohort. Data regarding the Progression Free Survival are pending at the time of this report. Conclusions: These retrospective data suggest that personalized genomic cancer medicine approaches result in decreased morbidities and cost savings compared to standard chemotherapeutic approaches. In patients with advanced cancer, genomic-based treatments appear to be cost-effective, safe and viable option for treating advanced cancer patients. Additional data regarding survival outcomes are required to determine efficacy of treatment.
Troxacitabine administered by continuous infusion (CI) is well tolerated and effective in adults with relapsed or refractory acute myeloid leukemia (AML)
Authors: G. Roboz, J. Jolivet, M. Kelner, S. Allen-Bard, L. Park, N. A. Lokker, N. A. Giese, E. J. Feldman
Journal: Journal of Clinical Oncology (2005)

6597 Background: Troxacitabine, the first β-L-deoxycytidine nucleoside analog to demonstrate potent anti-tumor activity has unique mechanistic and pharmacokinetic properties that overcome resistance observed with the β-D-analogs, cytarabine and gemcitabine. Recent studies show that troxacitabine has a slower rate of entry into cells because it is not recognized by nucleoside transporters. Therefore, prolonged, continuous exposure greatly increases cytotoxicity and results in potent in vivo anti-tumor activity. Initial studies with bolus administration demonstrated encouraging but modest clinical efficacy in AML patients. To potentially increase clinical efficacy a new evaluation of troxacitabine by CI was done. Methods: Adults (20 M, 12 F) of median age of 67 and ECOG performance status of 1 (range 0–2) with previously treated AML were entered. Troxacitabine was administered at a dose of 10.1 mg/m2 by CI for 2,3,4,5 and 6 days in successive cohorts such that cumulative doses ranged from 20.2 to 60.6 mg/m2. This dose was well tolerated over 5 days and therefore, this duration was maintained while the daily dose was escalated to determine the MTD. Results: Troxacitabine was given as 1st salvage therapy in 12 patients (CR <12 months), as 2nd salvage in 9 patients, and as 3rd salvage in 10 patients. Troxacitabine non-hematologic toxicities primarily included skin rash, hand-foot syndrome, and mucositis. Dose-limiting mucositis was observed at 60.6 mg/m2 given over 6 days. The MTD of troxacitabine over 5 days has not yet been reached with patients at a cumulative dose of 70 mg/m2. Of the 23 evaluable patients treated at doses of 40.4 mg/m2 or higher, 4 CR and 2 CRp have been observed. The steady-state plasma concentrations achieved by CI over 5 days equaled those shown to be efficacious in preclinical models and correlate with clinical activity. Conclusions: Troxacitabine can be safely administered over 5 days by CI to dose levels >50% higher than those achievable by bolus administration. The 26% overall response rate observed in these refractory and relapsed AML patients is encouraging. No significant financial relationships to disclose.
Predictive value of Fc gamma receptor IIIa genotype in response to conatumumab in three phase II studies.
Authors: Y. Pan, V. Haddad, T. Sabin, N. Baker, Y. J. Hei, F. Galimi, J. Graves, C. Huang, S. Cottrell
Journal: Journal of Clinical Oncology (2011)

3103 Background: Conatumumab (AMG 655) is an investigational, fully human monoclonal agonist IgG1 antibody that selectively binds to DR5, activates caspases, and induces apoptosis in cancer cells. Conatumumab requires cross-linking to FcγRIIIa, a receptor for the Fc region of immunoglobulin G, to induce apoptosis in vitro. A polymorphism in the FCGR3A gene leads to high and low affinity forms of the receptor. We investigated whether FCGR3A genotype was predictive of response to conatumumab in three phase II clinical trials. Methods: Samples from randomized, placebo-controlled studies in non-small cell lung cancer (NSCLC), metastatic colorectal cancer (mCRC), and metastatic pancreatic cancer (mPC) were genotyped for the FCGR3A V158F SNP (rs396991) for 55, 137, and 156 subjects, respectively. Cox proportional hazard modeling was used to determine the significance of the interaction between treatment effect and FCGR3A V allele (high affinity) carrier status. Results: After adjusting for major prognostic factors, conatumumab treatment was associated with a trend of better overall survival (OS) than the control patients among the V carriers but not the F allele homozygotes in the NSCLC trial. In mCRC, OS was significantly longer in conatumumab-treated than the control patients among the V carriers, while no OS benefit was observed with conatumumab in the F homozygotes. In the mPC trial, there was no apparent impact of the polymorphism on the treatment effect of conatumumab on OS. Conclusions: FCGR3A V allele carriers trend toward stronger treatment effect on OS, suggesting that the high affinity form of FcγRIIIa may be associated with enhanced responsiveness to conatumumab. The effect of this polymorphism in response to conatumumab and other antibodies reliant on FcγRIIIa cross-linking may be different among different tumor types and needs further validation in additional studies. Cox model for interaction of treatment effect and genotype. Study No. of deaths total patients) Hazard ratio (CI)— V carriers Hazard Ratio (CI)— FF P value (adjusted) NSCLC 93 (137) 0.72 (0.43, 1.23) 1.37 (0.66, 2.86) 0.068 mCRC 38 (156) 0.39 (0.16, 0.93) 2.89 (0.83, 10.07) 0.013 mPC 45 (55) 1.25 (0.58, 2.69) 0.58 (0.21, 1.58) 0.11