tbuckley/cabot-search huggingface dataset:
Phase I trial of TAS-102 and concurrent radiation therapy for patients with locally recurrent, unresectable or metastatic, rectal cancer.
Authors: Joleen Marie Hubbard, Alexis Diane Leal, Christopher Leigh Hallemeier, Daniel H. Ahn, Nitin Mishra, Nathan R. Foster, Tanios S. Bekaii-Saab, Axel Grothey
Journal: Journal of Clinical Oncology (2018)

TPS3623 Background: After primary therapy for rectal cancer (chemotherapy, surgery, and/or radiotherapy), 7-10% of patients will develop locally recurrent disease. Re-irradiation +/- resection of recurrent rectal cancer is possible for select patients. Trifluridine/tipiracil (TAS-102) is a combination nucleoside analog and thymidine phosphorylase inhibitor (TPI) with activity in colorectal cancer refractory to fluoropyrimidines. Trifluridine has a similar mechanism of action as the fluoropyrimidines, which are known radiosensitizing agents, and pre-clinical data shows TPI can potentiate the effects of radiation on colon cancer cell lines. TAS-102 in combination with radiation therapy may have a synergistic effect treating recurrent rectal cancers in patients previously exposed to a fluoropyrimidine. The primary objective of this trial is to determine the maximum tolerated dose and dose-limiting toxicity of TAS-102 when administered in combination with concurrent radiation therapy in patients with locally recurrent rectal cancer. Methods: This is a phase I trial with a standard 3 + 3 dose escalation design (see table). All patients will receive TAS-102 administered PO twice daily on days 1-5 and days 8-12. All patients will also receive radiation therapy at a dose of 300 cGy/day, for a total dose of 3000 cGy in 10 fractions, Monday through Friday for days 1-5 and days 8-12. Patients ≥ 18 years with histological confirmation of locally recurrent rectal adenocarcinoma within the pelvis after primary therapy are eligible. Patients with pelvic disease that is resectable or unresectable and metastatic disease outside the pelvis are allowed. Patients with the first occurrence of rectal cancer amenable to treatment with trimodality therapy will be excluded. Prior treatment with TAS-102 and cancer treatment ≤ 28 days prior to registration is not allowed. Patients with prior pelvic radiation therapy > 54 Gy are ineligible. This trial is currently accruing patients to the first cohort. Clinical trial information: NCT03297710.Dose Level Dose **TAS-102 Dose (2X daily) -1 -57% 15 mg/m2 0* -43% 20 mg/m2 1 -29% 25 mg/m2 2 -14.3% 30 mg/m2 3 100% 35 mg/m2 *Starting dose. **Round dose to the nearest 5 mg. Maximum dose 80 mg.
Abstract 18902: CT Derived Atherosclerotic Plaque Burden and Morphology Are Associated With Impaired Myocardial Blood Flow Using [15O]H2O PET and Fractional Flow Reserve, Independent of Luminal Obstruction
Authors: Roel S Driessen, Wynand J Stuijfzand, Pieter G Raijmakers, Ibrahim Danad, James K Min, Jonathon A Leipsic, Marc C Huisman, Adriaan A Lammertsma, Albert C Van Rossum, Niels van Royen, Paul Knaapen
Journal: Circulation (2016)

Introduction: Next to coronary lesion severity, atherosclerotic plaque characteristics may influence downstream myocardial perfusion. Hypothesis: We assessed the hypothesis that quantitative plaque burden and plaque morphology using coronary computed tomography angiography (CCTA) is associated with quantitative myocardial perfusion using [15O]H2O positron emission tomography (PET) as well as invasively derived fractional flow reserve (FFR). Methods: 208 patients (63% men, age 58 ± 8.7 years) with suspected coronary artery disease were prospectively included. All patients underwent 256-slice CCTA, [15O]H2O PET, and invasive FFR measurements. CCTA derived quantitative plaque burden and morphology were assessed using commercially available software. Results: Atherosclerotic plaques were present in 179 (86%) patients and 414 of 610 (68%) evaluable coronary arteries. On a per-vessel basis, traditional coronary stenosis indices such as plaque length and volume, minimal lumen area, plaque burden, and stenosis pe...
Differential crizotinib efficacy among ROS1 fusion partners in ROS1-positive non-small cell lung cancer.
Authors: Shun Lu, Ziming Li
Journal: Journal of Clinical Oncology (2017)

9067 Background: ROS1 rearrangement non–small-cell lung cancers can be effectively treated with ALK inhibitor such as crizotinib, but the response magnitude and duration are heterogeneous. Several ROS1 fusion partners have been identified, but few studies have focused on the effects of different fusion partners on the efficacy of crizotinib. Methods: Among 49 RT-PCR assay ROS1 rearrangement patients treated with crizotinib between April 2014 and November 2016, we identified 36 patients with tumor specimens that could be evaluated for the presence of different ROS1 fusion partners by Sanger sequencing. Patients continued crizotinib until RECIST-defined progression. We retrospectively evaluated the efficacy of crizotinib on the basis of the objective response rate(ORR), progression-free survival (PFS) and overall survival (OS) according to the different ROS1 fusion partners. Results: The most frequent ROS1 fusion partner was CD74-ROS1 (CD74-E6; ROS1-E34) in 16 patients (44.4%), followed by EZR-ROS1 (EZR-E10; ROS1-E34) in 7 patients (19.4%), SDC4 (SDC4-E2; ROS1-E32) in 4 patients (12%), SLC34A2-ROS1 (SLC34A2-E14del; ROS1-E32) in 2 patients (5.6%) and TPM3 (TPM3-E8; ROS1-E35) in 2 patients (5.6%). We also found that SDC4+EZR (SDC4-E2; ROS1-E32/EZR-E10; ROS1-E34) in 2 patients (5.6%), dual CD74-ROS1 (CD74-E6; ROS1-E32/34) in 2 patients (5.6%), CD74+SDC4 (SDC4-E2; ROS1-E32/CD74-E6; ROS1-E34) in 1 patient (2.8%). ORR was 83.3% in all patients, whereas it was 70.58% and 92.35% in the CD74 and non–CD74 groups, respectively (P = 0.17). The median PFS was longer in non–CD74 than in those with CD74 (median PFS, 17.67 months [95% CI, 12.14 to 23.19 ] vs 19.30 months [95% CI, not reached], respectively; P = 0.405) with no statistical significance. The median OS was significantly longer in patients with non–CD74 than in those with CD74 (median OS, 28.07 months [95% CI, 23.93 to 32.1] vs not reached, respectively; P = 0.043). Multivariable analysis identified 1 significant factor associated with OS, brain metastasis before crizotinib treatment (P &lt; 0.001). Conclusions: Our results indicate the better OS of crizotinib in patients with non–CD74 vs CD74. The ROS1 fusion partnerS might affect the efficacy of ALK-TKIs.
A randomized phase II study of trastuzumab and pertuzumab (TP) compared to cetuximab and irinotecan (CETIRI) in advanced/metastatic colorectal cancer (mCRC) with HER2 amplification: S1613.
Authors: Kanwal Pratap Singh Raghav, Shannon L McDonough, Benjamin R. Tan, Crystal S. Denlinger, Anthony Martin Magliocco, Nicholas W. Choong, Nicolas Sommer, Frank A. Scappaticci, Danae Campos, Katherine A Guthrie, Scott Kopetz, Marwan Fakih, Howard S. Hochster
Journal: Journal of Clinical Oncology (2018)

TPS3620 Background: Despite advances in systemic therapy, few patients are cured, creating a large unmet need for strategies targeting novel signaling and resistance pathways. The HER2 pathway, which has been successfully targeted in breast and gastric cancer, is one such unique potential target in mCRC. HER2 amplifications (HER2amp) have been identified in a small but distinct subset (6-8%) of KRAS wild-type mCRC. HER2amp is associated with resistance to anti-EGFR therapy (cetuximab/panitumumab) and short progression-free survival (PFS) ( < 3 mos.) (Raghav ASCO 2016). Preliminary clinical data (MyPathway Study) has shown promising activity of dual-anti-HER2 inhibition using TP in HER2amp and KRAS wild-type mCRC (Response rate 52%, 95% CI 31 - 72%; and median PFS 5.7 months, 95% CI 4 – 12 mos.) (Hurwitz GIASCO 2017). Methods: S1613 is a multicenter, randomized phase 2 study assessing efficacy of TP relative to CETIRI in HER2amp mCRC. This is a 2 step study. All anti-EGFR naïve mCRC patients (pts) without known activating mutations in KRAS/NRAS/BRAF will be screened in step 1 for HER2amp by a central lab using immunohistochemistry and dual-probe in-situ hybridization. Screening can be performed at any time, even during treatment on 1st/2nd line of therapy. If HER2amp positive, pts will be randomized in step 2 after progression on 1st/2nd lines of therapy to either TP [pertuzumab (840mg loading dose + 420mg every 3 weeks) and trastuzumab (8mg/kg loading dose + 6mg/kg every 3 weeks)] or CETIRI [irinotecan (180 mg/m2 IV every 14 days) and cetuximab (500 mg/m2 IV every 14 days)]. Prior irinotecan is allowed. Crossover to TP will be allowed after progression on CETIRI arm. A total of 122 eligible patients will provide 80% power to detect an increase in median PFS to 5.1 months from 3 months (HR 0.59) based on a two-sided type I error of 5%, 33 months of accrual and 7 months of follow-up. The primary endpoint of PFS will be analyzed in all eligible patients per intent-to-treat. Randomization will be stratified by prior use of irinotecan and HER2/CEP17 ratio. The study is now activated and open to enrollment to all NCI - NCTN institutions. Clinical trial information: NCT03365882.
Which is better? Carboplatin versus cisplatin for locally advanced cervical cancer: Peruvian experience.
Authors: Natalia Valdivieso, Victor Paitan Amaro, Connie Rabanal Carretero, Nathaly Poma Nieto, Claudio J. Flores, Jule Franve Vasquez Chavez, Manuel Alvarez Arredondo, Adelaida Heredia Zelaya, Luis Mas
Journal: Journal of Clinical Oncology (2017)

e17004 Background: Cervical cancer occurs mostly in developing countries, being locally advanced cancer the majority. The standard treatment is chemo-radiation with platinum salts. Carboplatin is commonly used because of its synergy with radiation reported in other malignancies and its safe toxicity profile, besides it is not clear use of it. We want to evaluate the equivalence of cisplatin versus carboplatin concurrent to radiotherapy in terms of response rates and toxicity profile. Methods: Retrospective observational analysis in women older than 18 years old, with diagnosis of locally advanced cervical cancer (stages Ib2 – IVA) at the “Instituto Nacional de Enfermedades Neoplasicas”, Lima – Peru, between 2014 and 2015. We determined two arms; cisplatin 40 mg/m2 per week for 5 weeks and Carboplatin 2AUC per week for 5 weeks. Both groups were given concurrent to radiotherapy. Results: 247 patients were evaluated, 119 received carboplatin and 128 cisplatin. Both groups have similar characteristics; median age was 50 years, the most frequent hystologic type was squamous cell carcinoma in 90.7%, and TNM stage IIB 59.5%, IIIB 27.5% and IV-A 2.8%. The complete response (CR) rate in cisplatin group was of 88.3% and carboplatin group 73.9% (p = 0.004). The toxicity profile was similar in both groups, except to renal toxicity (Cisplatin: 0% vs. Carboplatin: 5%, p = 0.010) and diarrhea (Cisplatin:26.6% vs. Carboplatin: 16.0%, p = 0.043). In patients with CR, the recurrence rate does not present a significant difference according to treatment schedule (Cisplatin: 15.9% vs. Carboplatin: 13.6%, p = 0.651). Overall survival (OS) and disease free survival (DFS) are on going. Conclusions: Our study found that cisplatin had better response rates than carboplatin with similar toxicity profile. This intervention to be remains to be clarified with following-up.
Cost effectiveness (CE) of blinatumomab (BLIN) vs inotuzumab ozogamicin (INO) in adult patients with relapsed or refractory (R/R) acute lymphoblastic leukemia (ALL) with no more than one prior salvage therapy (S0/S1) from a US payer perspective.
Authors: Thomas E. Delea, Xinke Zhang, Jordan Amdahl, Diana Boyko, Franziska Severin, Marco Campioni, Ze Cong
Journal: Journal of Clinical Oncology (2018)

e18895 Background: To estimate Incremental CE Ratio (ICER = ∆Cost / ∆QALY [Quality Adjusted Life Year]) of BLIN vs INO in adults with R/R S0/S1 ALL based on matching-adjusted indirect treatment comparison (MAIC) of TOWER and INO-VATE trials from a US payer perspective. Methods: CE was estimated by a partitioned-survival model with outcomes based on published aggregate data from INO-VATE (cutoff: 01/05/2017) and individual patient data from TOWER weighted to match patients in INO-VATE using MAIC. Three analyses were conducted based on alternative approach for the MAIC (anchored through Standard of Care [SOC] vs unanchored), proportional hazards (PH) assumptions, and reference overall survival (OS) distributions. Complete remission rates, utilities, duration of therapy, and use of subsequent therapies also were MAIC adjusted. Due to inconsistent definitions of event-free survival (EFS) between the trials, EFS was assumed to be equal for BLIN and INO complete responders. Costs were estimated from published sources and included those of BLIN/INO treatment (medication & administration), important adverse events (costs of adverse events for BLIN were assumed to be captured in costs of hospitalization), stem-cell transplant, salvage therapy, and terminal care. Utilities were based on EORTC-8D values derived from EORTC QLQ-C30 assessments in TOWER. A 50-year time horizon was used. Results: In all analyses, BLIN was more costly and more effective than INO. The ICER for BLIN vs INO ranged from $16,814 to $57,310. Conclusions: For various approaches for conducting MAIC of BLIN vs INO, BLIN was cost effective vs INO in R/R ALL adults with S0/S1 from a US payer perspective. Analysis No. Anchored MAIC PH Assumed for BLIN vs SOC PH Assumed for INO vs SOC Reference OS (Distributions) Hazard Ratio Applied (95%CI) ∆Cost ($)* ∆QALY* ICER ($) 1 Y Y Y TOWER BLIN (Gompertz) INO vs BLIN 1.39 (0.89-2.17) 29,780 1.77 16,814 2 Y Y N INO-VATE SOC (Lognormal Mix Cure) BLIN vs SOC 0.53 (0.36-0.77) 30,894 0.54 57,310 3 N Y N TOWER BLIN (Gompertz) INO-VATE INO (Lognormal Mix Cure) N/A 29,775 1.74 17,095 *Discounted @3%
Is US Medical Care Inefficient?
Authors: Victor R. Fuchs
Journal: JAMA (2018)

Is US Medical Care Inefficient?Is US medical care inefficient?Many health policy experts maintain it is, whereas others prefer a verdict available to juries in Scotland-"not proven."The correct answer is that no industry is either efficient or inefficient in abstract terms.Efficiency describes the relation between the input(s) and output(s) of a product (eg, an engine), an organ (eg, the heart), or an industry.Each industry has a unique set of inputs and outputs and set of technologic, economic, and sociopolitical constraints.It may be possible, however, to compare the efficiency of US medical care with the efficiency of medical care in other countries if the inputs, outputs, and constraints are sufficiently similar; if they differ, it is possible to adjust for those differences.For example, per capita spending for medical care in the United States is approximately double the spending in the United Kingdom, but life expectancy at birth is almost 3 years lower in the United States than in the United Kingdom.Some of the difference is probably attributable to a poverty rate of 17% in the United States compared with only 10% in the United Kingdom.Using a slightly different metric, the poverty rate in the United States
B-cell receptor–mediated NFATc1 activation induces IL-10/STAT3/PD-L1 signaling in diffuse large B-cell lymphoma
Authors: Li Li, Jun Zhang, Juan Chen, Zijun Y. Xu-Monette, Yi Miao, Min Xiao, Ken H. Young, Sa Wang, L. Jeffrey Medeiros, Michael Wang, Richard J. Ford, Lan V. Pham
Journal: Blood (2018)
Relationship between out-of-pocket spending and drug value for oral oncolytics reimbursed by commercial insurers: 2007-2014.
Authors: Lisa Rotenstein, Stacie Dusetzina, Nancy Lynn Keating
Journal: Journal of Clinical Oncology (2017)

6524 Background: With total and out-of-pocket (OOP) spending for oral oncolytics rising, there is increased interest in choosing oncology treatments based on their clinical value relative to cost. We sought to determine if OOP spending varied for higher versus lower-value oral oncology drugs reimbursed by commercial insurers. Methods: This was a retrospective analysis of commercial insurer prescription drug claims filed between 2007-2014 for 13 oral oncolytics approved before 2009. We calculated mean monthly OOP payments for each patient. We then categorized oral oncolytics by their overall and progression-free survival benefits for each FDA-approved indication, using evidence from published studies. We assessed the relationship of survival benefit with mean monthly OOP payment, adjusting for demographic and plan characteristics. Results: Our population included 44,109 patients ages 18-65 (mean age = 52.5 years, SD = 9.4 years) with a cancer diagnosis who filled 731,261 prescriptions. The most commonly represented oncolytics were imatinib (37.4% of fills) and lenalidomide (17.7% of fills). Approximately 57.6% of fills were for drug-indication pairs with an overall survival benefit of 5+ months. In adjusted analyses, there was no significant difference in mean monthly OOP payment between drugs without evidence of benefit and those with 0-5 months progression-free survival benefit or 5+ months of overall survival benefit (p &gt; 0.05). Meanwhile, drugs with 5-10 months progression-free survival benefit or 0-5 months overall survival benefit had higher OOP payments than those without benefit (p &lt; 0.01). Conclusions: OOP payments for oral oncolytics were not clearly related to indication-specific value. This suggests that despite increased attention to value- and indication-based drug pricing, cost-sharing for oral oncolytics does not currently reflect these goals.
Immune toxicity in post autologous transplant patients treated with brentuximab vedotin in combination with immune checkpoint blockade.
Authors: Catherine S. Magid Diefenbach, Fangxin Hong, Richard F. Ambinder, Jonathon Brett Cohen, Kevin Andrew David, Ranjana H. Advani, Michael J. Robertson, Timothy S Fenske, Stefan K. Barta, Neal Palmisano, Jakub Svoboda, David S. Morgan, Reem Karmali, Brad Kahl, Stephen M. Ansell
Journal: Journal of Clinical Oncology (2018)

7538 Background: Emerging data suggests that checkpoint blockade therapy (CBT) subsequent to stem cell transplant (SCT) may cause significant immune-related toxicity. We evaluated whether increased patterns of immune toxicity were seen in post SCT patients treated on Arms A-F of E4412: A Phase I Study with an Expansion Cohort of the Combinations of Ipilimumab, Nivolumab and Brentuximab Vedotin in Patients with Relapsed/Refractory Hodgkin Lymphoma Methods: Transplant status of patients treated with brentuximab vedotin (BV) + ipilimumab (Ipi) (Arms A-C) or BV + nivolumab (Nivo) (Arms D-F) was recorded at study entry. Toxicity was graded according to CTCAE v4.0. Results: Eighteen of 42 patients enrolled on Arms A-F were post SCT; 15 autologous (ASCT) and 3 allogeneic (AlloSCT). There were no demographic differences between the SCT and all patients. No patients had active GVHD. In Arms A-C grade 3 toxicities (rash and allergic reaction), occurred in 20% (2/10) of SCT patients (8 ASCT, 1 AlloSCT) compared with 39% (9/23) of all patients; there were no grade 4 toxicities in SCT patients compared to 4% (1/23) of all patients. A higher incidence of grade-1-2 rash was noted in ASCT patients 70% vs 39% all patients; however there was no increase in diarrhea, arthritis, or uveitis. In Arms D-F there were no significant differences in high grade toxicities in ASCT 16% (1/6) vs. 21% (4/19) all patients; 50% (1/2) AlloSCT patients experienced grade 3 toxicity (pneumonitis, typhlitis). A second pneumonitis, grade 5, occurred in the non SCT population. There remainder of toxicities were grade 1-2 and were not significantly increased in the SCT patients. A transient and clinically insignificant elevation in transaminases was not increased in SCT 16% (3/19) compared to all patients 47% (9/19). Conclusions: CBT in combination with BV was well tolerated in the ASCT population, however larger studies are required to confirm this finding for AlloSCT patients. Investigation of dual CBT (Ipi + Nivo) in combination with BV in this population continues. Evaluation of the safety of CBT + BV in E4412 in the pre SCT setting is ongoing and will be combined with this data by the ASCO meeting. Clinical trial information: NCT01896999.
Effect of adding taxane to platin-5-fluorouracil combination on survival in elderly patients with advanced gastric cancer: A retrospective-multicenter study.
Authors: Meral Gunaldi, Fatih Kose, Nebi Serkan Demirci, Seyda Gunduz, Nuriye Özdemir, Hakan Kocoglu, Yildiz Okuturlar, Ali Murat Sedef, Dilek Erdem, Sema Sezgin Goksu, Gokmen Umut Erdem, Mustafa Yildirim
Journal: Journal of Clinical Oncology (2016)

e15572 Background: Advanced gastric cancer (AGC) has dismal prognosis and second leading cause of cancer related mortality. Platin-5-fluorouracil (PF) combination chemotherapy is the most widely used protocol, and addition of taxane seems to increase survival and toxicity rates in all age groups. We aimed to evaluate efficacy and toxicity of PFtax over PF in patients ≥ 65 years old and compare them with patients < 65years old. Methods: A total of 341 patients with AGC treated at six different oncology centers in Turkey between 2010 and 2014 were retrospectively evaluated. The study group was consisted of 234 patients < 65 years of age (group 1) and 107 patients ≥ 65 years of age (group 2). All patients’ data were statistically analyzed. Results: Median age of patients was 58.2 years. Mean follow-up time was 14.4 months. For entire group, progression-free survival (PFS) and overall survival (OS) were estimated as 9 and 13 months, respectively. PFtax provided significantly higher PFS and OS in group 1 (p: 0.0001 and p: 0.017), whereas it did not any benefit in group 2 (p > 0.05). Also adding taxane to PF did not increase grade 3-4 adverse events in all groups (p > 0.05) Conclusions: Addition of the taxanes to PF backbone shows significantly increase in PFS and OS in patients < 65 years of age. But, in contrast to patients < 65 years of age, triplet regimen with taxanes does not provide superior survival in patients ≥ 65 years of age.