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  • 1
    In: The Journal of Pain, Elsevier BV, Vol. 17, No. 4 ( 2016-04), p. S106-
    Type of Medium: Online Resource
    ISSN: 1526-5900
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2016
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  • 2
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 24_Supplement ( 2012-12-15), p. S3-2-S3-2
    Abstract: Introduction Patients with isolated local and regional recurrences (ILRR) of breast cancer (BC) have a high risk of developing distant metastasis and dying from BC. We investigated the impact of chemotherapy (C) on disease-free survival (DFS) and overall survival (OS) after ILRR. Methods Patients with resected ILRR were stratified according to prior chemotherapy (yes vs. no), ER and/or PgR status of the recurrent tumor (both negative vs. either positive), and location of recurrence (breast vs. scar/chest wall vs. lymph nodes). Radiation, hormone and HER2 directed therapies were delineated in the protocol. Participants were randomly assigned to receive C or none. Multidrug C for at least 4 courses was recommended. Drug selection was at the discretion of the investigator. Slow accrual led to premature closure of the trial before achieving the planned sample size of 265. Results The trial accrued 162 patients (C, 85; control, 77) from 2002–2010. The groups were balanced in regard to the characteristics listed in the table below. At a median follow up of 4.9 years, there were 24 (28%) DFS events and 9 (11%) deaths in the C group compared with 34 (44%) DFS events and 21 (27%) deaths in the control group, corresponding to a 5-year DFS of 69% vs. 57%, [DFS HR (C/control) = 0.59, 95% CI (0.35, 0.99)], p =0.046] and a 5-year OS of 88% vs. 76%, [OS HR (C/control) = 0.41, 95% CI (0.19, 0.89)], p =0.02] . The results remained significant for both DFS and OS in multivariable Cox proportional hazards modeling controlling for ILRR location, disease-free interval, ER status and prior adjuvant chemotherapy. Adjuvant C was particularly effective for women with ER-negative ILRR: 5-year DFS 67% vs. 35%, [DFS HR (C/control) = 0.32, 95% CI (0.14, 0.73)], p =0.007] and OS 79% vs. 69%, [OS HR (C/control) = 0.43, 95% CI (0.15, 1.24)], p =0.12] . Results for the ER-positive ILRR cohort were: 5-year DFS 70% vs. 69%, [DFS HR (C/control) = 0.94, 95% CI (0.47, 1.89)], p =0.87] and OS 94% vs. 80%, [OS HR (C/control) = 0.40, 95% CI (0.12, 1.28)], p =0.12] . Conclusion Adjuvant chemotherapy should be recommended for patients with completely resected isolated loco-regional recurrences of breast cancer, in particular, if the recurrence is not sensitive to endocrine therapy. Funding NCI PHS grants U10-CA-37377, -69974, -12027, -69651, CA-75362. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr S3-2.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
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    detail.hit.zdb_id: 410466-3
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  • 3
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2007
    In:  Journal of Clinical Oncology Vol. 25, No. 18_suppl ( 2007-06-20), p. 520-520
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 25, No. 18_suppl ( 2007-06-20), p. 520-520
    Abstract: 520 Background: DCIS patients treated with lumpectomy have a very favorable outcome but are at risk for IBTR. Local control is improved by radiotherapy (RT) and adjuvant tamoxifen (TAM). Local failures, specifically invasive IBTRs (I-IBTR), may impact on long-term outcome. We present long-term outcome results from a cohort of DCIS patients from two NSABP randomized trials. Patients and Methods: A total of 2,615 women with primary DCIS from NSABP B-17 and B-24 (randomized from 1985 to 1994) were included. Median follow-up was 〉 12 yrs. In B-17 treatment was lumpectomy (LO, 403) or lumpectomy with whole breast irradiation (LRT, 410). In B-24 patients received LRT (901) or LRT plus TAM [901]. Hazard ratio and cumulative incidence of IBTR were examined by treatment. Mortality hazard was evaluated in relation to prior IBTR. Results: IBTR was a first failure in 465 patients (243 invasive, 222 noninvasive). The 12 year cumulative incidence of all IBTRs was 32.9% for LO, 15.8% LRT, and 12.5% LRT+TAM. RT significantly reduced I-IBTR (LRT/LO hazard ratio (HR) = 0.39; 95% confidence interval (CI) =0.26 to 0.59). TAM conferred additional benefit on I-IBTR (LRT+TAM/LRT HR=0.68; 95% CI= 0.48 to 0.97). Overall mortality was low. Women with I-IBTR had a two-fold greater mortality risk relative to those without I-IBTR (HR=2.08; 95% CI = 1.46 to 2.98). The effect was greater for LRT patients (HR=3.04; 95% CI= 1.92 to 4.84) than for LO patients (HR=1.17; 95% CI = 0.57 to 2.39). For LRT+TAM patients, the effect was similar to that for LRT patients HR=1.91; 95% CI= 0.76 to 4.78). Conclusions: As in cases of I- IBTR after an invasive index tumor, the occurrence of an I-IBTR with a DCIS index tumor, particularly after RT, confers increased risk for subsequent mortality. No significant financial relationships to disclose.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2007
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  • 4
    In: Annals of Surgical Oncology, Springer Science and Business Media LLC, Vol. 24, No. 3 ( 2017-3), p. 660-668
    Type of Medium: Online Resource
    ISSN: 1068-9265 , 1534-4681
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2074021-9
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  • 5
    Online Resource
    Online Resource
    Elsevier BV ; 2014
    In:  Breast Diseases: A Year Book Quarterly Vol. 25, No. 4 ( 2014), p. 338-
    In: Breast Diseases: A Year Book Quarterly, Elsevier BV, Vol. 25, No. 4 ( 2014), p. 338-
    Type of Medium: Online Resource
    ISSN: 1043-321X
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2014
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  • 6
    In: Fertility and Sterility, Elsevier BV, Vol. 100, No. 3 ( 2013-09), p. S116-S117
    Type of Medium: Online Resource
    ISSN: 0015-0282
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2013
    detail.hit.zdb_id: 1500469-7
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2019
    In:  Cancer Research Vol. 79, No. 4_Supplement ( 2019-02-15), p. P2-09-11-P2-09-11
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 4_Supplement ( 2019-02-15), p. P2-09-11-P2-09-11
    Abstract: Introduction: Triple negative breast cancer (TNBC) accounts for approximately 15% of breast cancer diagnoses and is associated with a higher risk of recurrence and more aggressive course in the metastatic setting. Emerging data suggest that some patients with TNBC benefit from immune-based therapies targeting the anti-programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) axis, but success has been limited in poorly immunogenic tumors. Thus, combination therapies that drive an influx of CD8+ tumor infiltrating lymphocytes (TILs) and/or upregulate PD-L1 expression are required to increase response rates to these therapeutics. Intratumoral injection of plasmid IL-12 (tavokinogene telseplasmid; tavo) followed by electroporation (IT-tavo-EP) is a gene therapy approach that drives local expression of the proinflammatory cytokine, interleukin-12 (IL-12). Local expression of IL-12 is hypothesized to result in increased TILs and enhanced expression of proinflammatory cytokines, resulting in conversion of poorly-immunogenic/low TIL TNBC tumors into highly inflamed immunologically active lesions while demonstrating a high safety profile. Methods: OMS-I140 is a phase I, non-randomized, open-label study of IT-tavo-EP in patients with inoperable locally advanced, metastatic and/or treatment-refractory TNBC (NCT02531425). Eligible patients have pre-treated TNBC and at least 2 anatomically distinct cutaneous or subcutaneous lesions accessible for injection and electroporation, with or without other regional or distant metastases. 10 patients are planned for enrollment. IT-tavo-EP is administered on Days 1, 5 and 8 of a single 28-day cycle. Tavo is injected intratumorally (based on tumor volume) at a concentration of 0.5 mg/mL and immediately followed by co-localized electroporation (6 pulses at 1500 V/cm with 1-second intervals). Tumor biopsies are obtained at baseline and post-treatment on day 28 of both treated and untreated lesions to determine if this therapy can promote a pro-inflammatory molecular and histologic signature. Pain scores and adverse events are recorded. Results: To date, nine patients have completed study therapy. Reported treatment-related adverse events include pain associated with electroporation (grade 1) in 8 patients and fatigue (grade 1) in 1 patient. Median pain score (range 0-10) immediately after treatment was 2 (range 0-10) and 5 minutes post-treatment was 0 (range 0-6). In some patients, treatment-related increases in CD8+ TIL density have been observed by intratumoral chromogenic staining. Further immune profiling is being conducted to characterize the tumor microenvironment pre- and post-therapy. A subset of patients with treatment refractory TNBC received anti-PD-1 monotherapy as their immediate next therapy with clinical response observed. Updated data will be presented. Conclusions: Our data suggest that IT-tavo-EP is a safe and tolerable TIL stimulating therapy in TNBC. Further study of IT-tavo-EP in combination with pembrolizumab in pretreated metastatic TNBC is planned. Citation Format: Telli ML, Zablotsky K, Le MH, Canton D, Browning E, Bannavong D, Gargosky S, Wapnir I. Intratumoral tavokinogene telseplasmid and electroporation in pre-treated inoperable locally advanced or recurrent triple-negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-09-11.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
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    detail.hit.zdb_id: 410466-3
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  • 8
    Online Resource
    Online Resource
    Elsevier BV ; 1996
    In:  Placenta Vol. 17, No. 7 ( 1996-09), p. 479-486
    In: Placenta, Elsevier BV, Vol. 17, No. 7 ( 1996-09), p. 479-486
    Type of Medium: Online Resource
    ISSN: 0143-4004
    Language: English
    Publisher: Elsevier BV
    Publication Date: 1996
    detail.hit.zdb_id: 2002489-7
    SSG: 12
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  • 9
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2005
    In:  Journal of Clinical Oncology Vol. 23, No. 16_suppl ( 2005-06), p. 517-517
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 23, No. 16_suppl ( 2005-06), p. 517-517
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2005
    detail.hit.zdb_id: 2005181-5
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  • 10
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 4_Supplement ( 2019-02-15), p. OT2-06-03-OT2-06-03
    Abstract: Triple negative breast cancer (TNBC) accounts for 10-20% of breast cancer diagnoses and is associated with a high risk of recurrence and a more aggressive course in the metastatic setting. Emerging data suggest that some patients with TNBC could benefit from the addition of immune-based therapy due to the important role of tumor infiltrating lymphocytes (TILs) on outcome. Reports show that early-stage TNBC patients with at least 50% TILs demonstrate longer disease-free survival. Additionally, immune-modulating therapies, like the anti-PD-1/PD-L1 monoclonal antibodies, have demonstrated modest activity in the pre-treated metastatic TNBC population with objective response rates (ORR) & lt;10%, but appear to require an immunogenic tumor, characterized by CD8+ TILs, in order to be effective. Plasmid IL-12 (tavo) with electroporation (tavo- EP) is a gene therapy approach yielding sustained intratumoral expression of the proinflammatory cytokine IL-12. Combining tavo-EP with an anti-PD-1 therapy, such as pembrolizumab, may improve responses for TNBC subjects by potentially converting poorly-immunogenic/low TIL tumors into high TIL/immune-responsive tumors while providing a favorable side-effect profile. OMS-I141 is a phase 2, non-randomized, study of intratumoral tavo-EP with pembrolizumab in patients with locally-advanced, inoperable, metastatic and/or treatment-refractory TNBC. Key inclusion criteria include documented inoperable locally advanced or metastatic TNBC, at least 1 prior line of approved systemic chemotherapy or immunotherapy and an accessible lesion for intratumoral injection and electroporation. Eligible subjects will receive intratumoral tavo-EP to the accessible lesions on Days 1, 5 and 8 every 6 weeks and intravenous (IV) pembrolizumab (200 mg) on Day 1 of each 3-week cycle. The primary objective of the study is to assess the ORR by blinded independent central review based on RECIST v 1.1. Secondary objectives include assessment of safety and tolerability of the combined treatment, duration of response (DOR), ORR (investigator-assessed), immune ORR (iORR), progression-free survival (PFS), immune PFS (iPFS) and overall survival (OS). A Simon 2-Stage design will be employed and a total of 25 patients will be accrued. In Stage 1 up to 15 subjects will be enrolled. If the number of responders meet the pre-specified number (N ≥ 1/15), then the enrollment for Stage 2 will include an additional 10 subjects (for a total of ≥ 6 responders out of 25 subjects). For more information regarding the study, contact OncoSec at info@oncosec.com. Citation Format: Telli ML, Wapnir I, Vinayak S, Chang J, Alemany C, Twitty C, Gargosky S. A phase 2 study of intratumoral tavokinogene telseplasmid (tavo) plus electroporation with pembrolizumab in patients with inoperable locally advanced or metastatic triple negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT2-06-03.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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