tbuckley/cabot-search huggingface dataset:
Abstract 12117: Global Real-World Data on the Use of Lomitapide in Treating Homozygous Familial Hypercholesterolemia: The Lomitapide Observational Worldwide Evaluation Registry (LOWER), Two-Year Data
Authors: James Underberg, Christopher Cannon, Dominique Larrey, Lukas Makris, Charles Schwamlein, Helen Phillips, LeAnne Bloeden, Dirk Blom
Journal: Circulation (2016)

Introduction: Lomitapide is a microsomal triglyceride transfer protein inhibitor indicated as adjunctive therapy for adults with homozygous familial hypercholesterolemia (HoFH). LOWER is a global observational registry to prospectively assess long-term, safety and effectiveness of lomitapide in clinical practice. Adult HoFH patients treated with lomitapide in clinical practice are eligible. Results: As of March 1, 2016, 143 patients had been enrolled in the USA, Canada, EU and Taiwan (Table); 139 patients had lomitapide exposure data (median 17.7 months, range 0.3-35.9 months). Globally, median lomitapide dose was 10 mg QD (range 5 mg QOD-40 mg QD, 6-33 months). A ≥ 50% reduction in LDL-C at any time post-baseline was measured in 58% of patients; 62% of patients achieved LDL-C &lt; 100 mg/dL and 37% achieved LDL-C &lt; 70 mg/dL. AEs were experienced by 73% of patients; GI disorders were the most common (45%). Serious AEs occurred in 21 (15%) patients. Thirty-three (24%) patients discontinued lomitapide because of an AE. Events of special interest comprised: major adverse cardiovascular events (11 patients, resulting in 2 deaths); hepatic events (19 patients, 6 discontinuations); GI events (20 patients, 16 discontinuations); oncologic events (2 patients: 1 pancreatic mass [diagnosis unconfirmed], 1 mediastinal B-cell lymphoma); 1 pregnancy; no coagulopathy events. Liver function tests were always performed per the label in 48% of patients. Peak ALT and AST was normal in 35% of patients and ≥ 3x ULN in 21% (among which 5% had ≥ 5x - &lt;10x ULN). No cases of Hy’s Law were recorded. Conclusions: The LOWER registry demonstrated safety and efficacy consistent with product labeling in patients treated with lomitapide for up to 3 years, but efforts are needed to improve prescriber adherence to recommended hepatic safety monitoring. There were no new safety signals and LDL-C reduction was consistent and robust, with 62% of patients achieving LDL-C &lt; 100 mg/dL.
Functional and oncologic outcomes of radical trachelectomy in early-stage cervical cancer: A prospective multicentric cohort of 61 patients.
Authors: Vincent Balaya, Lea Rossi, Charlotte Ngo, Anne-Sophie Bats, Patrice Mathevet, Fabrice Lecuru
Journal: Journal of Clinical Oncology (2017)

5529 Background: The aim of this study was to assess the post-operative morbidity of patients who have undergone a radical trachelectomy for early-stage cervical cancer and the oncologic outcomes. Methods: We retrospectively analyzed the data of two prospective trials on sentinel node biopsy for cervical cancer (SENTICOL I &amp; II). Patients underwent a radical trachelectomy for early-stage cervical cancer between January 2005 and March 2012 from 8 French oncologic centers. Results: A total of 61 patients have undergone a radical trachelectomy: 41 patients by laparoscopic-assisted vaginal way, 7 patients by total laparoscopic way, 11 patients by total vaginal way and 2 patients by laparotomy. The median age was 33 years (range = 22-68 years). 88.5 % of patients had a stage IB1 disease. There were 63.9% of epidermoid carcinoma and 34.4 % of adenocarcinoma. Eighteen patients (29.5%) had only a sentinel lymph node biopsy and 43 patients (70.5%) had an additional pelvic lymphadenectomy. The median follow-up was 46 months (range = 0-85 months). Twenty patients (32.8%) had a urinary complication. There were 12 cases of urinary infections (19.6%), 6 cases of dysuria (9.8%), 3 cases of urinary incontinence (4.9%), and one case of ureteral fistula (1.6%). Nine patients had a major neurologic complication (14.7%): the genito-femoral nerve was injured in 4 cases (6.5%) and the obturator nerve was injured in 5 cases (8.2%). Sixteen patients (26.2%) presented a lymphovascular complication. There were 12 cases of limb lymphedema (19.7%) and 5 cases of pelvic lymphocyst (8.2%). During the follow-up, 3 patients (4.9%) had a local recurrence and two patients died : one from a breast cancer and one from a liver metastasis. Conclusions: The radical trachelectomy is a feasible and safe alternative option for young patient with a early-stage cervical cancer in order to preserve their fertility. See table. [Table: see text]
Phase 1b results of avelumab in patients (pts) with previously treated metastatic melanoma enrolled in the JAVELIN Solid Tumor trial, including updated subgroup analyses.
Authors: Ulrich Keilholz, Janice M. Mehnert, Sebastian Bauer, Hugues Pierre Bourgeois, Manish R. Patel, Donald Gravenor, John J. Nemunaitis, Matthew H Taylor, Lucjan Wyrwicz, Keun Wook Lee, Vijay Kasturi, Kevin M. Chin, Anja von Heydebreck, James L. Gulley
Journal: Journal of Clinical Oncology (2018)

e21531 Background: Avelumab is a human anti–PD-L1 IgG1 monoclonal antibody approved for the treatment of metastatic Merkel cell carcinoma and advanced urothelial carcinoma progressed on platinum therapy. Here, we report phase 1b data for avelumab in a cohort of pts with previously treated metastatic melanoma. Methods: Pts with unresectable stage IIIC/IV melanoma progressed after ≥1 line of therapy for metastatic disease received avelumab 10 mg/kg IV Q2W until progression, unacceptable toxicity, or withdrawal. Assessments included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Results: As of Dec 31, 2016, 51 pts were treated and followed up for a median of 24.2 mo (range, 16.1–31.5). Pts had received a median of 2 prior lines of therapy (range, 0-4), including ipilimumab (ipi; n = 26 [51.0%]). The ORR was 21.6% (95% CI, 11.3-35.3). Median duration of response was not estimable (NE; 95% CI, 2.6 mo-NE). Median PFS was 3.1 mo (95% CI, 1.4-6.3); the 6-mo PFS rate was 39.2% (95% CI, 25.2-52.9). Median OS was 18.5 mo (95% CI, 9.3-NE); the 12-mo OS rate was 62.3% (95% CI, 46.9-74.4). In pts with non-ocular melanoma (n = 35), the ORR was 31.4% (95% CI, 16.9-49.3) vs 0% in pts with ocular melanoma (n = 16; 7 pts [43.8%] had stable disease). Of 39 PD-L1–evaluable pts, those with PD-L1+ tumors (≥1% cutoff [n = 19]) had an ORR of 42.1% (95% CI, 20.3-66.5) vs 0% (95% CI, 0-16.8) in pts with PD-L1− tumors (n = 20); in pts whose tumors were PD-L1–unevaluable (n = 12), the ORR was 25.0% (95% CI, 5.5-57.2). In pts who received prior ipi (n = 26), the ORR was 30.8% (95% CI, 14.3-51.8). 39 pts (76.5%) had a treatment-related (TR)AE, most commonly infusion-related reaction (25.5%), fatigue (17.6%), and chills (11.8%). 4 pts (7.8%) had a grade ≥3 TRAE. 5 pts (9.8%) had an immune-related TRAE; all were grade 1/2. No TR deaths occurred. Conclusions: Avelumab showed durable responses, promising survival outcomes, and an acceptable safety profile in pts with previously treated metastatic melanoma. Subgroup analyses suggested meaningful activity in pts with non-ocular tumors, PD-L1+ tumors, or prior ipi therapy. Clinical trial information: NCT01772004.
駆虫薬ピルビニウムパモ酸塩、6‐(ジメチルアミノ)‐2‐[2‐(2、5‐ジメチル‐1‐フェニル-1h‐ピロール‐3‐イル)‐1‐メチル‐キノリニウムパモエート塩によるグルコース飢餓時の選択毒性を介した抗癌療法の新規戦略
Authors: Esumi H, Lu J, Hanaoka T
Journal: Clinical Cancer Research (2003)
Uptake and efficacy of using a state quitline to address tobacco use by cancer patients treated in community cancer centers.
Authors: Anna E Schulze, Karen Brown, Polly Hager, Laura Petersen, Hilary Baca, Louise Bedard, Graham W. Warren
Journal: Journal of Clinical Oncology (2018)

e18530 Background: Smoking by cancer patients and survivors causes adverse outcomes. Cancer treatment guidelines recommend evidence-based cessation support for all patients who use tobacco. However, there is little information on using existing state quitlines to provide support for cancer patients during and following cancer treatment. Methods: The Michigan Cancer Consortium (MCC), Michigan Department of Health and Human Services (MDHHS), Michigan Oncology Quality Consortium (MOQC), and National Jewish Health (NJH) began a partnership in 2012 to facilitate standardized tobacco assessments and documentation, evidence-based treatment including counseling and pharmacotherapy via a referral to an existing quitline, and follow-up for cancer patients across community cancer centers in Michigan. Reported are program results. Results: Initial enrollment of patients occurred through 18 oncology practices. Practices were provided training on the Ask-Advise-Refer model for tobacco treatment, patient materials, prepared referral sheets, monthly reports, and de-identified comparative data for quality improvement opportunities. Patients were provided free nicotine replacement and behavioral counseling via the quitline. Through 2017, a total of 4,347 cancer patients were referred to the quitline representing 17% of all Michigan quitline callers, an increase from 5.2% in 2012. Between 2013-17, a total of 2,291 nicotine replacement shipments were placed to enrolled patients. Prior to program implementation, subjective MOQC chart audits demonstrated that less than 15% of patients identified as tobacco users were referred for cessation support. A survey of Michigan cancer survivors found that referrals to cessation support increased from 60% in 2013 to 79.5% in 2016. Six-month follow-up of cancer patients enrolled in the quitline demonstrated a 26.3% quit rate. Conclusions: Partnering community oncology practices with quitlines can significantly increase access and delivery of evidence-based support. Results support integration of existing cessation resources into oncology practice to facilitate broad uptake.
Outpatient intra-arterial chemotherapy without radiation therapy for stages II and III oral cancer: A new treatment to improve quality of life and reduce irradiation-related complications.
Authors: Masatoshi Ohmae, Itsuro Kato, Yusei Fujita, Hiroo Takaoka, Noritoshi Meshii, Ayako Takasu, Mitsuhiro Nakazawa
Journal: Journal of Clinical Oncology (2017)

e17567 Background: We developed a superselective intra-arterial chemotherapy (iaCT) approach to oral cancer, in which an intra-arterial catheter is retrogradely inserted through the superficial temporal artery and/or occipital artery with concurrent radiation therapy (RT). This approach remarkably improves the curative effect, but it decreases patients’ quality of life (QOL) because of prolonged hospitalization, severe stomatitis, lifelong dry mouth, dysgeusia, and radiation osteonecrosis of the maxillo-mandibular bone. Methods: This study assessed our new outpatient iaCT (op-iaCT) approach involving a subcutaneous infusion reservoir without concurrent RT. We included 23 patients, 11 with stage II and 12 with stage III oral cancer, and they were treated with the op-iaCT approach without concurrent RT. Using this approach, the chemotherapeutic agent was intra-arterially administered at the Outpatient Chemotherapy Center of Rinku General Medical Center. Results: The response rate to this approach was 100%, and all patients had a complete response. Four patients with secondary regional lymph node metastasis underwent neck dissection. Twenty patients were disease-free without an irradiation-related complication, whereas 3 patients died of distant metastasis (2) or local recurrence (1). With the exception of ambulatory visits twice per week for 3 weeks, patients’ activities of daily living (ADLs) were mostly unaffected. Moreover, patients rarely complained of dry mouth or dysgeusia, and they were free from radiation osteonecrosis after cancer therapy. Additionally, they did not develop oral dysfunction related to radical operation. Conclusions: In this approach, the catheter is implanted subcutaneously; therefore, common catheter-related issues rarely occur, resulting in good maintenance of ADLs. Moreover, patients can avoid the side effects of RT. Consequently, patient’s QOL improves and medical expenses decrease. Thus, our new op-iaCT approach improves QOL and the curative effect in patients with oral cancer if their ambulatory and performance status is good.
ENCORE 601: A phase 2 study of entinostat in combination with pembrolizumab in patients with microsatellite stable metastatic colorectal cancer.
Authors: Nilofer Saba Azad, Keisuke Shirai, Autumn Jackson McRee, Mateusz Opyrchal, Douglas Buckner Johnson, Peter Ordentlich, Susan Brouwer, Serap Sankoh, Emmett V. Schmidt, Michael L. Meyers, Melissa Lynne Johnson
Journal: Journal of Clinical Oncology (2018)

3557 Background: In studies reported to date, no objective responses have been observed with PD-1 inhibitors in advanced/metastatic CRC (mCRC) pts with microsatellite stable (MSS)/mismatch repair proficient (pMMR) tumors. About 95% of mCRC pts have this phenotype; additional strategies are needed to improve effectiveness of immunotherapies in these pts. Entinostat (ENT), an oral, class I-selective histone deacetylase inhibitor, enhances anti-PD-1 activity by downregulation of immunosuppressive cell types in the tumor microenvironment in vivo and has shown promising activity with pembrolizumab (PEMBRO) in pts with melanoma and lung cancer. This study evaluates the safety and efficacy of ENT + PEMBRO in MSS/pMMR CRC pts. Methods: This study is a multi-cohort, Simon 2-stage, phase II trial. Main eligibility criteria for pts in the CRC cohort are: documented MSS/pMMR status, ≥1 prior regimen in the metastatic setting, and no prior anti-PD-(L)1 therapy. All pts received ENT 5 mg PO QW + PEMBRO 200 mg IV Q3W. The primary endpoint is objective response rate (ORR) as assessed by irRECIST. Results of the first stage are reported. Results: 16 pts were enrolled in Stage I with a median age of 58 (range 36-68) and 4 lines of prior therapy. Median follow up is 4.7 mos. To date, 2 pts had documented pseudoprogression (1 subsequently became a confirmed PR). As of data cutoff, 6 pts (1 PR, 5 SD) remain on study (median time on treatment of 18 wks). Common ( > 15%) treatment-related AEs include fatigue (37.5%), arthralgia (18.8%), and increased alkaline phosphatase (18.8%). Grade 3/4 related AEs were observed in 3 patients, and two deaths occurred on study – one due to sepsis secondary to cholangitis and the other due to progression. Serial blood and pre-treatment biopsies were obtained in all pts, with paired post-treatment biopsies in a subset of pts. Evaluation of PD-L1 expression, gene expression, myeloid and lymphoid compartments in biospecimens is in progress. Conclusions: ENT + PEMBRO demonstrates acceptable safety and encouraging preliminary activity in a small cohort of MSS/pMMR CRC pts, a patient population in which objective responses have not been reported with PD-(L)1 monotherapy. Clinical trial information: NCT02437136.
Elderly triple negative breast cancer patients: 15 years` Peruvian experience.
Authors: Gabriel Antonio De la Cruz Ku, Zaida Morante, Bryan Valcárcel, Daniel Enriquez, Eduardo Eyzaguirre, Antonella Saavedra, Maria Luján, Renato Luque, Cesar Razuri, David Guardamino, Hugo Alejandro Fuentes, Silvia P. Neciosup, Henry Leonidas Gomez
Journal: Journal of Clinical Oncology (2018)

e13129 Background: Triple-negative breast cancer (TNBC) is characterized by being an aggressive disease and diagnosed frequently in young population. Several studies are suggesting that the prognosis of older pts are different. The aim of this study was to determine the clinical characteristics and prognosis in Peruvian TNBC pts diagnosed after 65-years old. Methods: We retrospectively reviewed a database of 2007 pts diagnosed with TNBC at the “Instituto Nacional de Enfermedades Neoplasicas” (period 2000-2014). Survival differences were assessed by log-rank test. Prognostic factors were analyzed by using a Cox proportional hazards model. Results: A total 285 correspond to elderly pts. The median age was 71 years (range:65-95 years). Of pts, 48.8% were 65-70 years, 37.9% were 71-79 years, and 13.3% were 80 and older. Two pts were men. Chronic comorbidities were diagnosed in 44.9%. A total of 140 pts (51.8%) presented clinical stage (CS) T3-T4 and 58.8% had nodal involvement. At diagnosis, 27(9.6%), 97(34.4%), 135(47.9%) and 23(8.2%) had I, II, III and IV CS, respectively. The majority of pts underwent mastectomy (70.3%); 26.3% received neoadjuvant chemotherapy(NAC) and 37.9% adjuvant chemotherapy(AC). Otherwise, local relapse and distant metastasis were diagnosed in 117(41.1%) and 170(59.6%) pts, respectively. Lung was the more affected organ(11.6%), followed by bone(9.8%), liver(6%), and brain(6%). Median follow-up was 8.66 years. The 5- and 10-years DFS was 51% and 28%, respectively, while OS presented 52% and 40%, respectively. Older pts (≥80 years) had a worse DFS (64% vs 43% vs 21%, p < 0.001) and OS (58% vs 50% vs 33%, p = 0.003). Pts who received CT had a better OS (66% vs 43%, HR:0.52, 95%CI: 0.37-0.73, p < 0.001). At multivariate analysis, older age (65-70 vs ≥80, HR:5.28, 95%CI:1.90-14.66, p = 0.001) and N stage had a negative impact in DFS. Regarding to OS, older age (65-70 vs ≥80, HR:3.39, 95%CI:1.94-5.95, p < 0.001), T and N stage were associated with a poor prognostic, while CT and RT had a positive effect on OS. Conclusions: There are age-related differences in clinicopathological characteristics and prognosis. Older pts tend to receive less treatment which affects in their prognosis, especially among OS.
The effect of duvelisib, a dual inhibitor of PI3K-δ,γ, on components of the tumor microenvironment in previously untreated follicular lymphoma.
Authors: Carla Casulo, Andre Goy, Koen Van Eygen, Juan-Manuel Sancho, Mercadal Santiago, Rod Johnson, Kamal Bouabdallah, Kam Sprott, Ngocdiep T. Le, Jonathan A. Pachter, David T. Weaver
Journal: Journal of Clinical Oncology (2018)

7579 Background: Duvelisib (DUV), an oral dual inhibitor of PI3K-d,g, is clinically active in hematologic malignancies, including follicular lymphoma (FL), CLL, and T cell lymphoma (Flinn, 2017). PI3K-δ inhibition directly targets malignant cells and PI3K-γ inhibition disrupts the supportive tumor microenvironment. In the CONTEMPO trial (NCT02391545), previously untreated FL patients (pts) treated with DUV+rituxumab had an ORR of 93% (36% CRR) and pts treated with DUV+obinutuzumab had an ORR of 89% (41% CRR). In both treatment arms chemokines reflective of the tumor microenvironment were inhibited (Casulo, 2016). Methods: Ex vivo whole blood assays were conducted from healthy volunteers and 32 FL pts enrolled in CONTEMPO [pre-and post-DUV]. Ex vivo and in vitro PI3K-γ assays [(fMLP-stim monocyte and CXCL12-stim human T cell pAKT(S473), murine bone marrow monocyte migration, and macrophage polarization quantified by ARG1 expression] and PI3K-δ assays [LPS-stimulated monocyte pAKT(S473)] with PI3K-δ-selective [idelalisib (IDELA), TGR-1202, IPI-3063] and PI3K-γ-selective [IPI-549] inhibitors were compared. Results: DUV (IC50 0.4 ±0.1 mM) and IDELA (IC50 1.0±0.2 mM) potently inhibited LPS-induced human monocytes via PI3K-δ compared with the PI3K-γ selective IPI-549 (IC50 12±0.5 mM). For TGR-1202, the IC50 (25±8 mM) was below the RP2D clinical exposure. DUV (IC50 0.5±0.2 mM) and IPI-549 (IC50 1.6 ±0.2 mM) potently inhibited PI3K-γ dependent fMLP-stimulated human monocytes compared to IDELA (IC50 9.4±2.3) and TGR-1202 (IC50 55±16 mM). In FL pts treated with DUV, these PI3K-γ and PI3K-δ selective assays were inhibited 1-4 hours post treatment. Consistent with a PI3K-γ mechanism, both DUV and IPI-549 inhibited macrophage polarization to M2, reduced CXCL12-induced macrophage migration (DUV IC50 51 nM; IPI-549 IC50 85 nM), and blocked CXCL12-induced T cell migration (DUV EC50 128±39 nM; IPI-549 EC50 17±17nM), which was not observed with PI3K-δ inhibitor IPI-3063 (IC50 630±71nM). Conclusions: The disruption of PI3K-d,g function in FL pts treated with DUV supports its inhibition of the tumor microenvironment through cancer-supportive macrophages and T cells. Clinical trial information: NCT02391545.
PROCLAIM-001: A first-in-human trial to assess tolerability of the protease-activatable anti-PD-L1 Probody CX-072 in solid tumors and lymphomas.
Authors: Alexander I. Spira, Mark R. Middleton, Aung Naing, Karen A. Autio, John J. Nemunaitis, Johanna C. Bendell, Michael Gordon, Rachel W. Humphrey, Chihunt Wong, Naiyer A. Rizvi
Journal: Journal of Clinical Oncology (2017)

TPS3107 Background: CX-072 is a novel Probody therapeutic (PbTx) targeting PD-L1. PbTxs are fully recombinant antibody prodrugs designed to be converted to active antibodies by tumor-associated proteases that are highly expressed malignant tissue; the PbTx remains largely inactive in normal tissues. In pre-clinical tumor models, a PD-L1-directed PbTx provided comparable anti-tumor efficacy to its parental anti-PD-L1 antibody, but displayed reduced auto-immunity in a model of Type 1 diabetes. Based on these pre-clinical data, CX-072 has the potential to enable combination therapies that are otherwise poorly tolerated. This Phase 1/2 study (PROCLAIM-001 (PRObody CLinical Assessment In Man) assesses the tolerability and antitumor activity of CX-072 in humans with an emphasis on immune-related adverse events, particularly in combinations. CX-072 will be administered as monotherapy (Part A), in combination with 2 schedules of ipilimumab (Parts B1 and B2) and in combination with vemurafenib (Part C). The expansion cohort (Part D) will include CX-072 monotherapy in PD-L1 responsive tumor types. Methods: Key eligibility criteria are as follows: Parts A and B1: checkpoint inhibitor-naive patients with advanced, refractory solid tumor or lymphoma (unmeasurable disease allowed) for whom approved PD agents are not available. Part B2: advanced, refractory solid tumors or lymphomas with measurable disease who have progressed on a previous treatment with a PD-(L)1 inhibitor, but did not discontinue due to toxicity. Part C: checkpoint inhibitor, BRAF-inhibitor and MEK-inhibitor-naïve metastatic V600E BRAF-mutated melanoma. Patients without an active autoimmune disease, ongoing infection, and ECOG PS 0-1 may be eligible to participate in the study. Dose escalation follows the 3+3 design in all arms. Ipilimumab (Parts B1 and B2) is dosed at the approved 3 mg/kg every 3 weeks x 4. The dose of vemurafenib (Part C) is 960 mg/kg twice daily. Exploratory biomarkers are used to characterize tumor protease activity, inflammatory changes within the tumor, and CX-072 activation in tumor versus peripheral blood. Clinical trial information: NCT03013491.