tbuckley/cabot-search huggingface dataset:
Phase I/II canon study: Oncolytic immunotherapy for the treatment of non-muscle invasive bladder (NMIBC) cancer using intravesical coxsackievirus A21.
Authors: Hardev S. Pandha, Nicola E. Annels, Guy Simpson, Hugh Mostafid, Kevin J. Harrington, Alan Melcher, Mark Grose, Bronwyn Davies, Gough Geoffrey Au, Roberta Karpathy, Darren Shafren
Journal: Journal of Clinical Oncology (2016)

e16016 Background: CAVATAK is a novel, bio-selectedICAM-1 targeted immunotherapeutic Coxsackievirus A21 (CVA21). Surface ICAM-1 is up-regulated on NMIBC. CVA21 displays potent oncolytic activity against in vitro cultures of NMIBC cancer cells and ex-vivo human bladder tumor material. Combining CVA21 with mitocycin C (MMC) synergistically enhances viral replication by increasing expression levels of surface ICAM-1. In this two stage Phase I/II study, patients (pts) with NMIBC received neo-adjuvant CVA21 or low dose MMC plus CVA21 prior to routine surgical removal (TURBT). Methods: The CANON (CAVATAK in NON-Muscle invasive bladder cancer: NCT02316171) study investigated the tolerance of multiple escalating intravesicular (IV) doses of CVA21 in 16 first-line NMIBC cancer pts. Stage 1 Cohort 1 (n = 3) and Cohort 2 (n = 3), pts received single CVA21 administration at 1 x 108 and 3 x 108 TCID50 , respectively. In Cohort 3 (n = 3), pts received 2 doses of CVA21 at 3 x 108 TCID50 . Stage 2: Cohort 1 (n = 3), pts received a single CVA21 dose of 3 x 108 TCID50 and Cohort 2 (n = 3) with 2 doses of CVA21 at 3 x 108 TCID50 , both in combination with MMC (10mg). Cystoscopy photography was performed before and after treatment. IV treatment was followed by routine TURBT surgery after 8-11 days. TURBT tissues were analysed for CVA21 replication, apoptosis and the magnitude and specificity of immune cell infiltrate. Results: Data indicate general tolerance of IV CVA21 treatment. Serial cystoscopy identified viral induced surface haemorrhage and immune inflammation of the tumor micro-environment. Virus replication within tumor was highlighted by detection of secondary viral load peaks in the urine. TURBT tissue analysis displayed marked tumor specific viral replication and evidence of viral-induced apoptotic cell death in pts from mono- and combination therapy cohorts. Conclusions: Clinical activity of CVA21 was demonstrated by evidence of complete tumor response, viral replication and notable signs of viral-induced tumor inflammation. The observed tumor targeting and viral replication is likely to provide a strong signal in generating both a strong local and systemic anti-tumor immune response. Clinical trial information: NCT02316171.
Phase I/II, first in human trial of the Bruton’s tyrosine kinase inhibitor (BTKi) M7583 in patients with B cell malignancies.
Authors: Simon Rule, David Tucker, Anup Kalapur, Barbara Sarholz, Jürgen Scheele, Pier Luigi Zinzani
Journal: Journal of Clinical Oncology (2017)

e14101 Background: BTK is a cytoplasmic tyrosine kinase expressed in cells of hematopoietic origin that is involved in innate and adaptive immunity. BTK inhibition blocks B-cell functions including proliferation, antigen presentation, antibody production, and cell migration. The B-cell receptor pathway is implicated in the pathogenesis of B-cell malignancies such as diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and B-cell chronic lymphocytic leukemia (CLL). Small molecule BTKis are a new class of agent against B-cell malignancies; ibrutinib has recently been approved for the treatment of resistant/refractory CLL, MCL, and Waldenström’s macroglobulinemia (WM). This ongoing phase I/II clinical trial (NCT02825836) is designed to determine the safety, tolerability, PK, BTK occupancy, and preliminary antitumor activity of the highly selective BTKi M7583 in patients (pts) with refractory/resistant B cell malignancies. Methods: The trial is in two parts: a dose-escalation part for which pts with refractory/resistant B cell malignancies are eligible; and a dose-expansion part for which pts with DLBCL (ABC subtype) or MCL who have failed 1-3 prior lines of therapy are eligible. Pts in the dose-escalation part will be enrolled to sequential dose escalation, with ascending once-daily M7583 doses starting at 80 mg (3 initial days)/160 mg (full 28-day cycle) and increasing according to an adaptive Bayesian design. Results: Three pts have been enrolled to treatment with M7583 80/160 mg (Table). All 3 patients have had an objective response or stable disease and relevant clinical benefit.Conclusions: M7583 appears to have a favorable benefit:risk profile, with an efficacy signal at a dose of 80 mg (3 initial days)/160 mg (full cycle) with objective response or clinical benefit. Clinical trial information: NCT02825836. [Table: see text]
Exploratory phase II evaluation of cabozantinib in recurrent/metastatic uterine carcinosarcoma (CS): A study of the Princess Margaret, Chicago, and California phase II consortia.
Authors: Victoria Mandilaras, Neesha C. Dhani, Qian Tan, Angela Jain, Carolyn Johnston, Hal W. Hirte, Katia Sonia Tonkin, Mihaela C. Cristea, Koji Matsuo, Marcus O. Butler, Stephanie Lheureux, Julia V. Burnier, Lisa Wang, Anjali Mehta, John Joseph Wright, Amit M. Oza
Journal: Journal of Clinical Oncology (2017)

5587 Background: Carcinosarcoma (CS) is a rare ( &lt; 5%) aggressive subtype of endometrial cancer (EC). Patients (pts) with progression on platinum-based chemotherapy (CTX) have limited options, there is no standard 2 nd line treatment and median progression-free survival (PFS) is &lt; 2months (mt), 6-mt PFS less than 20%. Limited molecular data on CS aligns with epithelial EC, providing rationale for evaluating similar strategies such as targeting MET and angiogenesis. Cabozantinib (cabo) is multi-targeted tyrosine kinase inhibitor against MET, VEGFR, TIE2, RET, AXL and KIT. Methods: PHL-86 (NCI#9322/NCT01935934) is a multi-centre, non-randomized, phase II trial of cabo (60 mg oral daily dose on a 28-day cycle) in EC pts recurring within a year of adjuvant CTX or with progression after 1 st line of CTX for metastatic disease. Pts with rare histology including CS, were enrolled in an exploratory cohort. Activity of interest for further evaluation was defined as 4 responses (either partial response [PR] or 12-wk PFS) out of 10 pts of a given histotype. CT scans were performed after cycle 3 and every 2 cycles thereafter. Results: From 2013 to 2016, 32 pts were treated in the exploratory cohort, 19 pts with CS. Median age was 66 years (range 25-75); prior treatment included CTX (17: 1 line, 6: 2 lines) and/or radiation (11). Fifteen pts were evaluable for response, with 1 PR (7%) and 8 pts with 12-wk PFS (53%). Median PFS was 3 mt (95% CI: 2.7 – 4.6) with estimated 6-mt PFS of 13% (2 to 33%). Toxicity evaluation is available for 19 pts. Common events were fatigue and GI upset. Most frequent &gt; Grade3 toxicities were hypertension (5), anemia (4), diarrhea (2). Four pts had GI fistula (2) or perforation (2). Mutation profiling in archival tissue showed TP53 (73%), PIK3CA (40%), KRAS (27%), PTEN(13%) with &gt; 1 mutation present in 14/15 pts analyzed. The 1 pt with no somatic mutations had a PR (31% decrease) on cabo (PFS 6.7mt). Conclusions: Cabo in CS cohort met the predefined endpoint for further evaluation and compares favourably with other agents in this poor prognosis disease. Larger studies are required to define depth and durability of response and identify relevant biomarkers. Clinical trial information: NCT01935934.
P01.112 The challenge of health utility values for glioblastoma patients with long-term survival
Authors: C Proescholdt, J Kelly, A Kinzel
Journal: Neuro-Oncology (2018)

Glioblastoma (GBM) is the most aggressive form of primary brain cancer in adults. The EF-14 trial was the first randomized controlled trial to report a GBM survival rate greater than 10% at 5-years. In order to estimate the economic impact of new treatments, the quality-adjusted life year (QALY) has been developed and is widely used in health economic literature. For the assessment of QALYs, health utility values are needed. Utilities are preference weights for health states and are measured on a cardinal scale of 0–1, with 0 indicating death and 1 indicating full health. They are determined either through direct elicitation methods (e.g. time trade-off, standard gamble) or generic preference-bases measures like Health Utilities Index (HUI), Short form 6D (SF-6D) or the EuroQoL-5D (EQ-5D). However, in oncology they do not account for patients with long-term survival. This approach may understate QALYs, as a patient alive 5-years after diagnosis will be assigned the same utility value as a patient recently diagnosed. We performed a comprehensive review of the published literature regarding health utility values in GBM patients through a Pubmed search using “glioblastoma” AND “health utility” OR “glioblastoma” AND “health utilities” OR “glioblastoma” and “health preference” as the search terms. The search yielded a total of 77 publications. Only 3 publications turned out to be relevant in health economic context. All three publications use utilities for GBM derived from the same source (Garside et al.). Estimates of utility were therefore obtained from the NHS Value of Health Panel (VoHP) of which 36 members (out of 93) familiarized with the standard gamble method for preference elicitation, responded rating a total of 9 descriptive health state scenarios. This approach does not capture the presence or absence of AEs over time but assumes the constant presence of the AEs during the respective state. Additionally, Garside assumed a constant decline in QoL of patients in “progressive” state which may particularly not be adequate for long-term surviving patients experiencing a sustained stable disease after initial progression. The published health economic evaluations for GBM treatments rely on health utilities as determined by Garside et al through the standard gamble method in 36 healthy panel members of the UK National Health System. There are no published utilities for GBM in a general population sample. There are no reports that adequately adjust the utility scores with time from diagnosis. Deriving and validating health preference-based measures from existing condition-specific questionnaires (e.g. the QLQ C-30 with it’s brain cancer module BN20) specifically for GBM would be beneficial. This approach would allow for adjusted utility values with time from diagnosis, it’s feasibility has already been shown in multiple myeloma.
EFS24 as a predictor of outcome in a population-based cohort of patients with DLBCL in British Columbia (BC).
Authors: Line Srour, Yvonne Y. Zheng, Alina S. Gerrie, Kerry J. Savage, David W. Scott, Diego Villa, Graham W Slack, Randy D. Gascoyne, Joseph M. Connors, Laurie Helen Sehn
Journal: Journal of Clinical Oncology (2016)

7569 Background: Patients (pts) with diffuse large B cell lymphoma (DLBCL) who achieve event-free survival at 24 mo (EFS24) have been shown to have a subsequent overall survival (OS) similar to that of the general population (Maurer JCO 2014). We aimed to confirm these results in the province of BC. Methods: The BC Cancer Agency Centre for Lymphoid Cancer database was used to identify all pts with DLBCL including primary mediastinal LBCL (PMBCL) treated with R-CHOP btw 2001 and Sept 2015. OS of these pts was compared to expected survival determined from BC life tables (accounting for age at diagnosis (dx), gender and year of dx) to obtain a standardized mortality ratio (SMR) of observed:expected deaths. Event decomposition was performed using a competing risk approach. Results: 2046 pts were identified: median age 65 y (range 14-94); 56% males; 56% stage III-IV; 41% IPI 3-5; 31% bulky disease ≥ 10 cm; PMBCL, n = 138. Cell of origin was available in 601 pts; Lymph2Cx assay, n = 381; IHC Hans algorithm, n = 220; GCB, n = 358; ABC/non-GCB, n = 203; unclassifiable, n = 40. Median follow-up for living pts was 64 mo (range, 1-176). 682 (33%) pts relapsed and 742 (36%) died. 82% of relapses occurred within 2 y of dx. The 5y risk of relapse was 33% (95% CI 31-35%) but decreased to 11% (95% CI 9-13%) in pts who achieved EFS24. This risk remained higher than the 5y risk of death from other causes (9%, 95% CI 8-11%) in pts achieving EFS24. At dx, the SMR was 3.89 (95% CI 3.62-4.18, p < .0001) compared to 1.75 (95% CI 1.54-2.00, p < .0001) for pts achieving EFS24. This remained true regardless of age ( ≤ 60 vs > 60), stage and IPI risk. Interestingly, pts with GCB subtype (SMR 1.18, 95% CI 0.78-1.73, p = .42) and pts with PMBCL (SMR 1.82, 95% CI 0.67-3.98, p = .22) achieving EFS24 did have an OS comparable to the general population. Conclusions: In our population-based cohort of DLBCL pts treated with R-CHOP there remains an increased risk of death at EFS24 compared to an age and gender matched general population. This is in contrast to what has been previously reported and appears to be due to an ongoing risk of relapse as well as deaths from other causes. However, subgroup analyses suggest that pts with GCB subtype and PMBCL achieving EFS24 have an OS comparable to the general population.
Neoadjuvant ipilimumab + nivolumab (IPI+NIVO) in palpable stage III melanoma: Updated data from the OpACIN trial and first immunological analyses.
Authors: Elisa A. Rozeman, Christian U. Blank, Alexander Christopher Jonathan Van Akkooi, Pia Kvistborg, Lorenzo Fanchi, Johannes V. Van Thienen, Bauke Stegenga, Brian Lamon, John B. A. G. Haanen, Ton Schumacher
Journal: Journal of Clinical Oncology (2017)

9586 Background: The combination of IPI+NIVO induces high response rates and improved overall survival in late stage melanoma. T cell checkpoint inhibition is of greatest value at the moment of TCR triggering and therefore dependent on the amount of antigen present, indicating that adjuvant immunotherapy may work most efficiently, when initiated prior to surgery. Methods: Two-arm Phase 1b feasibility trial of 20 high risk AJCC stage IIIB and IIIC melanoma patients with palpable nodal disease receiving the combination of IPI 3mg/kg and NIVO 1mg/kg, either adjuvant four courses after surgery, or split two courses neo-adjuvant and two courses adjuvant. Results: In this update all 20 patients are evaluable. Neo-adjuvant application of IPI+NIVO was feasible and no surgery-associated adverse events were attributed to (neo-)adjuvant therapy. 18/20 patients had to stop early due to grade 3/4 toxicities. Neo-adjuvant IPI+NIVO reduced tumor load in 8/10 patients (3 pCR, 4 near-pCRs [minimal remaining micrometastases], 1 pPR [75% reduction], 1 SD and 1 PD). To date, after a median follow-up of 45 weeks (range 13-74), none of the responders in the neoadjuvant arm has relapsed. Relapse was observed for both non-responders within the neo-adjuvant arm and for 3 patients within the adjuvant arm. TCR sequencing and MHC tetramer-based analysis to compare the induction and expansion of tumor (neo-)antigen-specific T cell responses between both treatment arms are underway and will be presented. Conclusions: The combination of IPI+NIVO in the (neo-)adjuvant treatment setting for high risk stage III melanoma patients is feasible and induces very frequent responses. At the same time, severe grade 3/4 toxicity is more frequent than expected from stage IV melanoma patient study data. These results indicate that IPI+NIVO is a promising combination for neo-adjuvant treatment in stage III melanoma. Adjusted combination schemes are currently tested in the phase 2 OpACIN-neo trial, with the aim of reducing toxicity while preserving efficacy. Clinical trial information: NCT02437279.
Role of volume reduction gastrectomy according to tumor location in patients with gastric cancer with a single non-curable factor: Supplementary analysis of REGATTA trial (JCOG0705/KGCA01).
Authors: Kazumasa Fujitani, Masanori Terashima, Han-Kwang Yang, Junki Mizusawa, Toshimasa Tsujinaka, Kenichi Nakamura, Hiroshi Katayama, Hyuk-Joon Lee, Jun Ho Lee, Yoshiaki Iwasaki, Ji Yeong An, Akinori Takagane, Young-Kyu Park, Seung Ho Choi, Kyo Young Song, Mitsuru Sasako
Journal: Journal of Clinical Oncology (2018)

e16038 Background: Chemotherapy (CTX) is the standard of care for incurable advanced gastric cancer (AGC). REGATTA trial, which investigated survival benefit of reduction gastrectomy (Gx) in patients (pts) with AGC with a single non-curable factor, failed to demonstrate the superiority of Gx followed by CTX over CTX alone. However, there was a significant interaction between the treatment effect and tumor location in the subset analysis. In addition, treatment effect appeared to be different between Japan and Korea. So, the aim of this supplementary analysis was to explore the subgroups for which volume reduction Gx was beneficial with special reference to the tumor location and country in REGATTA trial. Methods: REGATTA trial was a randomized phase III trial at 44 institutions in Japan, Korea, and Singapore. Patients with AGC with a single non-curable factor were randomly assigned in each country to CTX alone or Gx plus CTX. The primary endpoint was overall survival (OS). In this analysis, OS was compared according to tumor location, country, and operative procedure. Results: A total of 175 pts (95 in Japan, 80 in Korea) was randomized to CTX alone (86 pts) or Gx followed by CTX (89 pts). MST was 16.6 months in CTX alone and 14.3 months in GX plus CTX (HR 1.09, 95% CI: 0.78–1.52, p = 0.70) (primary analysis). In subgroup analysis according to the country, OS curves were separated between the arms, worse in Gx plus CTX arm in Japan (HR 1.32, 95% CI: 0.85-2.05), whereas, that was not, almost similar between the arms in Korea (HR 0.85. 95% CI: 0.52-1.40). HRs according to tumor location were 2.23 in upper third, 0.95 in middle third, and 0.63 in lower third, respectively. OS tended to be better in pts who received distal GX compared with CTX alone (HR = 0.69), and worse in pts who received total GX compared with CTX alone (HR = 1.34). This trend was more remarkable in Korea than in Japan. Conclusions: Primary CTX is a standard of care for AGC; however, it would be still an open question whether volume reduction Gx have a survival benefit when the tumors located at the distal stomach for which the pts receive distal Gx especially in Korean population. Clinical trial information: UMIN000001012.
Prevalence of Cannabis Use in Electronic Cigarettes Among US Youth
Authors: Katrina F. Trivers, Elyse Phillips, Andrea S. Gentzke, Michael A. Tynan, Linda J. Neff
Journal: JAMA Pediatrics (2018)

Karen A. Cullen, PhD; Andrea S. Gentzke, PhD; Michael D. Sawdey, PhD; Joanne T. Chang, PhD; Gabriella M. Anic, PhD; Teresa W. Wang, PhD; MeLisa R. Creamer, PhD; Ahmed Jamal, MBBS; Bridget K. Ambrose, PhD; Brian A. King, PhD
Enrolment of adolescents and young adults with cancer (AYAWC) to clinical trials at the Children’s Hospital of Eastern Ontario (CHEO).
Authors: Sarah Lum, Isabelle Laforest, Kenneth Tang, Lesleigh S. Abbott
Journal: Journal of Clinical Oncology (2017)

e18043 Background: Five-year survival among AYAWC has seen less improvement than in other age groups. One hypothesized reason is low accrual to clinical trials, for which the reasons need further determination. Our objectives were to determine the enrolment of AYAWC on treatment clinical trials at CHEO, a tertiary care pediatric hospital in Ottawa, Canada and to determine barriers to enrolment of AYAWC compared to younger patients. Methods: A retrospective chart review of patients diagnosed at CHEO over 10 years from January 1, 2006 to December 31, 2015 was performed. AYAWC included 15-18 year olds, and younger patients included 0-14 year olds. Patients 18 years and older are treated at adult centers. The number of patients enrolled on an upfront treatment clinical trial was collected while those not enrolled were reviewed for documented non-enrolment reasons. Clinical trials available at CHEO during this time period were also recorded. Results: A total of 733 patients were diagnosed with 96 AYAWC and 637 younger patients. The proportion of patients enrolled on clinical trials was 19.8% (19) AYAWC and 27.3% (174) younger patients (p = 0.12). Trials were not available for 57.3% (55) of AYAWC and 53.7% (342) of younger patients for their disease type (p = 0.51). For the remaining 41 AYAWC, 46.3% were enrolled. For AYAWC not enrolled, 40.9% had a reason documented: for 22.2% a physician felt it was not in the patient’s best interest, 44.4% did not meet eligibility, 33.3% of families/patients declined. For the remaining 295 of younger patients that had trials available, 59% enrolled on a trial. For younger patients not enrolled, 25.6% had another reason documented: for 25.8% a physician felt it was not in the patient’s best interest, 45.2% did not meet trial eligibility, 25.8% of families/patients declined, 3.2% other reason. Conclusions: There were fewer AYAWC enrolled on trials compared to younger children. There were not fewer trials available for AYAWC patients than younger children. For patients not enrolled, the majority did not have an open trial available and otherwise, reasons for non-enrolment did not differ significantly between groups. Next steps could include data from local adult centers.
Phase 2 trial of brentuximab vedotin and gemcitabine for pediatric and young adult patients with relapsed or refractory Hodgkin lymphoma (HL): A Children’s Oncology Group (COG) report.
Authors: Peter D. Cole, Kathleen McCarten, Monika Metzger, Richard A. Drachtman, Terzah M. Horton, Qinglin Pei, Rizvan Bush, Susan Blaney, Brenda Weigel, Kara M. Kelly
Journal: Journal of Clinical Oncology (2017)

7527 Background: AHOD1221 (NCT01780662) tested Brentuximab vedotin (Bv) with gemcitabine (GEM) in children or young adults with HL. The primary objective was to describe the complete response (CR) rate within 4 cycles of therapy. Methods: Eligibility criteria included age ≤30 years; no prior Bv exposure; and primary refractory HL or advanced stage disease with early relapse. Each 21-day cycle consisted of Bv on day 1 at the recommended phase 2 dose (RP2D), 1.8 mg/kg and GEM 1000mg/m 2 on days 1 and 8. Patients were evaluable for response if they completed 4 cycles of Bv+GEM, had a CR after 2 cycles, or progressive disease at any time. Response was assessed after even cycles, and confirmed by central review. CR was defined by FDG-PET negativity (Deauville 1-2) regardless of residual lesion size. Results: 42 patients were treated with Bv+GEM. Median age was 17.4 years (range 5.4-28.7), and 23 (55%) were female. The majority (n=35; 83%) had primary refractory disease or early relapse &lt;6 months after completion of primary treatment. Common (&gt;10%) adverse events included maculopapular rash (36% in cycle 1), neutropenia (33%) and elevated serum transaminases (21%). GCSF-stimulated peripheral blood stem cell (PBSC) collection was successful in all patients (n=23) for whom it was attempted, with median total collection of 9.4x10 6 CD34+ cells/kg (range 3.5-36.8). 23 of 40 evaluable patients experienced a CR (58%; 95% CI 42-73%) within four cycles, and 6 had a partial response (PR), for an ORR of 73% (95% CI, 59-86%). For 4 patients with PR or stable disease, all target lesions were Deauville 3 or less after cycle 4, considered a CR by modern response criteria (Cheson et al. Blood 2016;128(21): 2489). Conclusions: Bv+GEM is a highly active combination for primary refractory or high-risk relapse of HL, with a CR rate exceeding that seen after either Bv (34%) or GEM (9%) alone. PBSCs can be collected successfully following Bv+GEM, making this an effective reinduction regimen when autologous stem cell transplantation is indicated. Compared to alternate retrieval regimens, Bv+GEM offers the advantage of avoiding agents associated with late treatment sequelae. Clinical trial information: NCT01780662.