bluuebunny/crossref_metadata_2025_split huggingface dataset:
LUX-breast 3: Randomized phase II study of afatinib alone or with vinorelbine versus investigator’s choice of treatment in patients (pts) with HER2-positive breast cancer (BC) with progressive brain metastases (BM) after trastuzumab or lapatinib-based therapy.
Authors: Joensuu Heikki , Ould Kaci Mahmoud 
Published: March 2020

TPS647 Background: Approximately 1/3 of pts with HER2-positive, advanced BC will develop BM with a poor prognosis. Efficacy of systemic therapies is limited since few drugs can readily cross the blood-brain barrier. BC BM represents a high unmet medical need for which novel targeted therapies are needed. Afatinib is a small molecule, irreversible ErbB Family Blocker that has shown preclinical activity in trastuzumab-resistant cell lines and HER2-positive tumor xenografts. Its clinical efficacy has been demonstrated in pts with heavily pre-treated, HER2-positive metastatic BC, who progressed after trastuzumab therapy, with partial responses in 10% and clinical benefit in 46% of pts. In a Phase I afatinib trial a sustained PR was observed in a NSCLC pt with BM, and in a phase II trial in NSCLC, pts with or without BM achieved comparable outcome on afatinib. The purpose of this study (NCT01441596) is to investigate whether afatinib alone or in combination with vinorelbine has any effect on HER2-positive BC with BM after failure of prior trastuzumab or lapatinib. Methods: Key eligibility criteria: histologically confirmed HER2-positive BC; recurrent/progressive BM during/after prior trastuzumab or lapatinib therapy; ≥1 measurable BM (≥10 mm on T1-weighted, gadolinium-enhanced MRI); extra-CNS lesions allowed; prior surgery, whole brain radiotherapy or stereotactic radiosurgery allowed; ECOG 0–2. Eligible pts are stratified by: ECOG score 0–1 vs 2; No of BM ≤ 3 vs >3; prior lapatinib therapy. Pts are randomized to (n = 40/arm): Arm A: afatinib (40 mg/d oral); Arm B: afatinib (40 mg/d oral) + vinorelbine (25 mg/m2/ week); Arm C: investigator’s choice of medical treatment approved for metastatic BC. Primary endpoint: pt benefit at 12 weeks (i.e. absence of CNS/extra CNS disease progression as per RECIST 1.1) and no tumour-related worsening of neurological signs/symptoms or increase in steroid dosage. Secondary endpoints: PFS, OS, safety and afatinib concentration in plasma/cerebrospinal fluid in ≥12 pts. The study began in October 2011 and enrollment is ongoing.
Docetaxel, carboplatin, trastuzumab, and bevacizumab (TCH+B) for early-stage HER2/neu(+) breast cancer and bone marrow micrometastases.
Authors: Baar Joseph , Silverman Paula , Budd G. Thomas , Gibson Laura , Meyerson Howard , Fu Pingfu , Diorio Dawn 
Published: March 2020

TPS655 Background: Bone marrow (BM) micrometastases confer a poor prognosis to early-stage breast cancer (BC) and HER-2/neu(+) BC is a high-risk phenotype. We have shown that BM-associated stromal cells support the survival of metastatic BC in microenvironmental niches and this activity is dependent on VEGF and CXCL-12. Therefore, the growth of nascent tumor cell clusters in BM might be impeded by disrupting stromal cells or their activating ligands, such as VEGF. There is also a positive association between HER-2/neu and VEGF expression in BC, thereby implicating VEGF in the aggressive phenotype of HER-2/neu overexpression. These observations support the use of combination therapies directed against both HER-2/neu and VEGF for the treatment of HER-2/neu(+) BC. We therefore hypothesize that an anti-VEGF agent (bevacizumab) given with docetaxel, carboplatin and trastuzumab (TCH) will eradicate the BM of HER-2/neu(+) BC micrometastases by disrupting stromal cell support within the micrometastatic BM niche. Methods: Subjects with AJCC Stage I-III HER2/neu(+) BC will undergo a single iliac-crest BM aspirate and biopsy. If the BM is positive for CK+ micrometastases, up to 17 patients will receive TCH+B therapy (docetaxel at 75 mg/m2 IV and carboplatin at AUC 6 IV given every 3 weeks for 6 cycles; trastuzumab at 4 mg/kg IV loading dose, then 2mg/kg IV every week; bevacizumab at 15 mg/kg IV every 3 weeks). Four weeks after the 6th cycle of therapy, a repeat BM aspiration and biopsy will be performed to score for response of BC micrometastases to therapy. Patients with a complete clinical response in BM will continue with trastuzumab every 3 weeks at 6 mg/kg to a total of 1 year. Patients with persistent micrometastases will receive both trastuzumab and bevacizumab every 3 weeks to a total of 1 year of therapy. These patients will then have a repeat BM aspirate and biopsy at the end of the 1 year to score for final response. The primary objective of this clinical trial is to determine clinical response against BC micrometastases in BM. The second objective is to investigate the specific contribution of VEGF and CXCL-12 signaling to BM support of micrometastatic BC cells.
HIT: A multicenter phase I-II study of trastuzumab administered by intrathecal injection for leptomeningeal meningitis of HER2+ metastatic breast cancer.
Authors: Gutierrez Maya , Fourme Emmanuelle , Taillibert Sophie , Le Rhun Emilie , Tredan Olivier , Gunzer Katharina , Dieras Veronique , Mefti Fawzia , Vago-Ady Nora , Tresca Patricia , Turbiez Isabelle , Paintaud Gilles , Brain Etienne 
Published: March 2020

TPS662 Background: Leptomeningeal metastases (LM) are commonly associated with breast cancer (BC), announcing short term prognosis that intrathecal (IT) chemotherapy poorly modifies. Incidence is particularly marked in HER2+ tumours. With the better control of extra-cerebral disease and prolonged survival yielded by intra-venous (IV) trastuzumab (T), the main hypothesis is that intra-cerebral recurrences are not reached by this high molecular weight (148 kD) monoclonal antibody. Analyses performed in cerebrospinal fluid (CSF) following IV T have shown low T levels, suggesting that LM of HER2+ BC would remain potentially sensitive to anti-HER2 agents as long as they could by-pass the meningeal blood brain barrier. Intraventricular (via Ommaya port) or IT administration of T would allow keeping control on LM progression through high T therapeutic concentrations in CSF. This prospective trial is the first phase I-II study sponsored by Institut Curie to investigate the safety and efficacy of the IT administration of T for HER2+ LM BC. Methods: Eligible patients must be 18+, have a diagnosis of LM either on CSF with HER2+ cytology or on clinical/MRI pictures of meningitis, and normal end-organ functions. The phase I cohort investigates the maximum tolerated dose (MTD) and recommended dose of T given weekly IT (or via Ommaya port) + hemisuccinate hydrocortisone 25 mg, while aiming at yielding a T target-concentration in CSF close to the plasma one (30 µg/mL) obtained with standard IV schedule. The MTD is defined as the highest dose level (DL) tested with ≥2 dose-limiting toxicity (DLT, any grade ≥3 NCI CTCAE v4.0 attributed to T) observed in ≤6 patients (3+3 Fibonacci dose escalation design, 4 DL 30-150 mg) with a maximum of 24 patients. The phase II cohort will investigate the efficacy of the recommended dose (DLMTD-1) defined in cohort I on neurological progression-free survival at 2 months, in ≤19 patients. Secondary endpoints include CSF and MRI response, quality of life, FCGR3A influence, and comparative CSF/plasma pharmacokinetics. Since study activation in May 2011, 5 patients have been included at DL1, 3 being evaluable for DLT. DL2 is now open for accrual.
The GALAXY Trial(NCT01348126): A randomized IIB/III study of ganetespib (STA-9090) in combination with docetaxel versus docetaxel alone in subjects with stage IIIB or IV NSCLC.
Authors: Goss Glenwood D. , Manegold Christian , Rosell Rafael , Fennell Dean Anthony , Vukovic Vojislav M. , El-Hariry Iman , Teofilovici Florentina , Enke Aaron S. , Ramalingam Suresh S. 
Published: March 2020

TPS7613^ Background: Hsp90 is a molecular chaperone required for proper folding and activation of many cancer-promoting proteins and is recognized as a key facilitator of cancer cell growth and survival. In pre-clinical models, Hsp90 inhibition causes degradation of multiple client proteins and leads to cancer cell death. Ganetespib is a resorcinolic Hsp90 inhibitor that has shown potent anti-tumor activity in patients with lung, breast, and other cancers that had progressed on standard treatment agents. Moreover, combination of ganetespib with docetaxel results in synergistic antiproliferative effects in several human non-small cell lung carcinoma (NSCLC) tumor xenografts. Ganetespib is well tolerated and is devoid of severe liver or common ocular toxicities that have been observed with some other Hsp90 inhibitors. Diarrhea is the most common adverse event and is manageable with appropriate supportive care. In a recent report, ganetespib administered at 200 mg/m2 weekly showed activity in pretreated patients with advanced NSCLC patients with ELM4-ALK translocation and KRAS mutations. Methods: Stage 1 (240 subjects): randomized, international open-label Phase 2B study in subjects that progressed on or after one prior systemic therapy for stage IIIB or IV NSCLC: patients are prospectively stratified for ECOG performance status, histology, total LDH, interval since diagnosis, and smoking status. Co-primary endpoints are PFS in the ITT population, and PFS in patients with KRAS mutations. Main secondary endpoints include ORR, disease control rate, OS and clinical activity in different molecular subtypes, including BRAF, HER2, EGFR, EML4-ALK. Patients on the control arm are treated with docetaxel 75 mg/m2 on day 1 of a three-week cycle. In the combination arm, ganetespib 150 mg/m2 is given on day 1 (with docetaxel) and day 15 of a three-week cycle. At the time of submission 90 subjects had been enrolled in Stage 1.
ELOQUENT-2: A phase III, randomized, open-label trial of lenalidomide/dexamethasone (Len/Dex) with or without elotuzumab (Elo) in relapsed or refractory multiple myeloma (RR MM) (CA204-004).
Authors: Lonial Sagar , Richardson Paul Gerard Guy , Moreau Philippe , Orlowski Robert Z. , San-Miguel Jesùs F. , Dimopoulos Meletios A. , Palumbo Antonio Pierangelo , Facon Thierry , Vij Ravi , White Darrell , Reece Donna Ellen , Singhal Anil , Kroog Glenn Scott , Kopit Justin , Anderson Kenneth Carl 
Published: March 2020

TPS8112 Background: MM remains incurable and patients (pts) typically relapse or become refractory to current treatments. Novel regimens are needed to improve pt outcomes. Elo is a humanized monoclonal IgG1 antibody targeting the cell surface glycoprotein CS1, which is highly expressed on >95% of MM cells. Len/Dex is approved for treatment of relapsed MM and an objective response rate (ORR) of ~60% was reported in phase III trials of this combination in RR MM. In a phase II study (N=73) of Elo (10 or 20 mg/kg) in combination with Len/Dex in pts with RR MM, the 10 mg/kg group (n=36) demonstrated an ORR of 92% and median progression-free survival (PFS) that was not reached after a median follow-up of 14.1 months. Encouraging activity was seen in patients with high-risk cytogenetics and/or stage 2-3 disease. Based on these data, a randomized, open-label phase III trial has been initiated to determine if the addition of Elo to Len/Dex will improve PFS in patients with RR MM compared with Len/Dex alone. Methods: Pts (N=640) with RR MM and 1-3 prior therapies are eligible, including pts with mild or moderate renal impairment. Pts are randomized in a 1:1 ratio to receive 28-day cycles of Len 25 mg PO (days 1-21) and Dex 40 mg PO (days 1, 8, 15 and 22) with or without Elo. Elo dose and schedule is 10 mg/kg IV on days 1, 8, 15, 22 in the first 2 cycles and on days 1 and 15 in subsequent cycles. Dex 8 mg IV + 28 mg PO is used during the weeks with Elo. Treatment will continue until disease progression, death, or withdrawal of consent. Patients will be followed for tumor response every 4 weeks until progressive disease and then survival every 12 weeks. The primary endpoint is PFS (90% power for a hazard ratio [experimental to control arm] of 0.74) and the secondary endpoints are ORR and overall survival. Exploratory endpoints are safety, time to response, duration of response, time to subsequent therapy, health-related quality of life, and pharmacokinetics and immunogenicity of Elo. Potential biomarkers will also be assessed. As of January 10th, 2012, 107 pts were enrolled and 68 pts were treated. NCT01239797.
PILLAR-2: A randomized, double-blind, placebo-controlled, phase III study of adjuvant everolimus in poor-risk diffuse large B-cell lymphoma (DLBCL).
Authors: Lin Tongyu , Zhu Jun , Bouabdallah Kamal , Ogura Michinori , Hino Masayuki , Kim Jin Seok , Wu Cassandra , Corrado Claudia , Witzig Thomas E. 
Published: March 2020

TPS8118 Background: Effective DLBCL adjuvant therapy after first-line chemotherapy is needed as high-risk DLBCL is associated with a poor 4-year overall survival (OS) rate (Sehn et al, Blood 2007;109:1857-61). In a phase II study of the oral mammalian target of rapamycin inhibitor everolimus in relapsed, aggressive non-Hodgkin lymphoma, DLBCL patients (n=47) had a 30% overall response rate (Witzig et al, Leukemia 2011;25:341-7). Methods: PILLAR-2 is an ongoing international, randomized, double-blind, phase 3 study designed to compare everolimus efficacy and safety with that of placebo in poor-risk DLBCL patients who achieved complete response (CR) with first-line rituximab-based chemotherapy (R-chemo) (ClinicalTrials.gov: NCT00790036; sponsor: Novartis Pharmaceuticals). Eligibility criteria include age ≥18 years; confirmed stage II bulky, III, or IV DLBCL and International Prognostic Index 3-5 at diagnosis; confirmed CR per revised International Workshop Response Criteria for malignant lymphoma (Cheson et al, J Clin Oncol 2007;25:579-86) after first-line R-chemo regimen completed 6-14 weeks before study drug start; Eastern Cooperative Oncology Group performance status ≤2; no ongoing or post–R-chemo radiation; and no myelosuppressive chemotherapy or biologic therapy within 3 weeks. Patients are randomized 1:1 to everolimus 10 mg once daily or matching placebo and treated for 12 months or until disease relapse, unacceptable toxicity, or death. Radiologic tumor assessment is performed at baseline, every 12 weeks during years 1 and 2, every 24 weeks during years 3 and 4, and annually thereafter until start of new anticancer therapy or 5 years after last patient randomization. The primary endpoint is disease-free survival (DFS). Secondary endpoints are OS, lymphoma-specific survival, and safety. Expected enrollment is 687 patients. Final analysis will be performed when 279 DFS events occur; survival follow-up will continue until 338 deaths occur and the last randomized patient has been followed for ≥5 years. Currently, 422 patients are enrolled. The data monitoring committee last reviewed the trial in July 2011 and recommended that it continue as planned.
Using cancer patient stories to “power” communication modules.
Authors: Lang Forrest , Sobol Joseph 
Published: March 2020

TPS9147 Background: Caring for patients with cancer poses great challenges to doctors’ communication skills. This project, funded by NIH-NCI, represents an innovative collaboration between ETSU faculty in medical oncology, family medicine, and storytelling. The team secures patients’ and caregivers’ cooperation in recording stories of their journeys with illness. These are the focus of a set of cancer communication modules, to be offered as educational experiences for medical students, residents, and oncology fellows. The modules in development address 1) breaking bad news, 2) living through treatment, 3) transitioning from curative to palliative care, 4) communicating with family, and 5) sensitivity to issues of religion and spirituality. Methods: A collaborative inter-professional team developed an interview protocol to facilitate sharing of cancer-themed narratives. Video records are transcribed and coded using N-Vivo 8. The rating team meets to identify video clips that speak powerfully to positive, negative, or ambivalent aspects of cancer communication. Selected patients are brought together into “story circles,” where additional narratives are gathered. The module development team uses these stories to create empathic involvement in viewers, and to sensitize them to effective and ineffective communication strategies and challenges surrounding critical moments in patients’ lived experience of cancer. Modules effectiveness is tested with 1) Family Medicine and Internal Medicine residents, 2) medical oncology fellows and 3) multi-professionals health students just completing a communication courses. Assessment includes a pre-test and post-test OSCE addressing a number of the challenging cancer communication moments. Eighty-four of a projected 100 patient interviews and twelve physician//faculty interviews have been recorded, and all have agreed to the use of their interview materials. Representative examples of recorded cancer stories will be presented to demonstrate their evocative and pedagogical value. Opportunities will be discussed for further uses of these and similar stories in collaborations between medicine and the arts and humanities.
The European InCASA telecare-telehealth electronic platform (ICT-FP7) for the daily assessment of symptoms, weight, and activity in cancer patients on chronotherapy at home.
Authors: Levi Francis , Arbaud Alexandre , Dispersyn Garance , Simon Jordi Rovira , Innominato Pasquale F. , Bossevot Rachel , Mocquery Magali , Plessis Virginie , Fursse Jo , Caprino Massimo 
Published: March 2020

TPS9154 Background: Self-rated symptoms contribute to the Quality of Life (QoL) of cancer patients (pts) and impact on prognosis. Behavioural functions are controlled by the circadian timing system (CTS), through a network of molecular clocks that time cellular proliferation and drug metabolism (Lévi et al. ARPT 2010). Chronotherapy aims at the reduction of treatment-related symptoms through the adjustment of chemotherapy delivery to the CTS. Cancer chronotherapy is delivered at home using programmable pumps, and avoids familial and social disruption. Telemedicine tools can provide continuous information on symptoms, behavior, QoL and CTS from non hospitalized pts. Methods: The inCASA platform enables telemonitoring of multiple functions in order to help physicians to detect early warning signals in pt condition at home, and prompt adequate and timely interventions. Our pilot site investigates the clinical relevance of daily teletransmitted self assessed symptoms, body weight and rest-activity circadian rhythm in cancer pts. This system was first well understood and accepted by 14 pts (9 male, 5 female, 43-77 years) at the outpt clinic, then used by 5 pts (4 male, 1 female, 61±13 years) at home daily for 6+ weeks, while receiving chronotherapy. The pilot phase will accrue 30 pts receiving chronotherapy at home from 03/01/2012. Pts will fill in the M.D. Anderson Symptom Inventory scale on a touch-screen device, measure their body weight using a Bluetooth scale and record their circadian rest-activity rhythm using an infrared wrist-watch accelerometer over 6-weeks. The data are transmitted to the platform, then to a web portal with secured access to be daily inspected by the oncology nursing and medical team. The modelling of these continuous records will define alert thresholds for nurse-controlled graded intervention decisions. Conclusion: The assessment criteria set forth for the inCASA solution will address the issues of pt autonomy, CTS entrainment in the pt usual environment, safety of chronotherapy delivery at home and treatment costs. Its use should induce important organisational changes and perception in healthcare professionals.
Treatment of pediatric lymphocyte predominant Hodgkin lymphoma (LPHL): A report from the Children's Oncology Group.
Authors: Appel Burton , Chen Lu , Hutchison Robert E. , Hodgson David C. , Ehrlich Peter , Constine Louis S. , Schwartz Cindy L. 
Published: March 2020

10000 Background: LPHL, an uncommon subtype of HL, typically presents with low stage disease and responds to regimens used for classical HL. Recurrence is uncommon, but second malignant neoplasms (SMN) or development of non-Hodgkin lymphoma (NHL) can occur. Therefore, reducing radiation exposure may be of benefit. We report the results of a prospective trial in which a selected subset of patients had surgery alone and the remainder were treated with limited chemotherapy +/- involved-field radiation therapy (IFRT). Methods: Patients ages 0-21 years with newly diagnosed, low risk LPHL were eligible for AHOD03P1. Low risk was defined as clinical Stage IA or IIA without bulk disease (mediastinal mass > 1/3 of the thoracic diameter or nodal aggregate > 6 cm). Patients with Stage IA LPHL with an unresected node or more than a single involved node or Stage IIA were treated with 3 cycles of AV-PC (doxorubicin/vincristine/prednisone/cyclophosphamide). Patients with Stage IA LPHL in a single node that was completely resected were initially observed without further therapy; those who recurred after surgery with low risk LPHL received AV-PC x 3. Patients with < complete response (CR) to AV-PC x 3 received 2100 cGY IFRT. Results: 180 eligible patients with low risk LPHL were enrolled and completed study therapy. 52 patients underwent initial surgery alone; their 3 year EFS = 81.5%. 137 patients received AV-PC x 3; 128 were treated at diagnosis and 9 upon relapsing after surgery alone. 11 patients receiving AV-PC had < CR and received IFRT. 12 first events occurred among these 137 patients (11 relapses and 1 SMN, a NHL). One relapse occurred in a patient who received IFRT. The median follow-up among the 125 remaining patients is 39 (range 3 -76) months. Current 4-year EFS estimate is 88.1% (95% CI: 79.5%-93.3%) for these 137 patients. 4 year EFS for the entire cohort of 180 patients = 86.2%; their overall survival (OS) is 100%. Conclusions: Pediatric LPHL patients have an excellent EFS with chemotherapy that is less intensive than standard regimens; >90% of patients can avoid RT. NHL as a first event may be related to the underlying LPHL and not an effect of treatment. The salvage rate for the few relapses is high, and OS to date is excellent. Clinical trial information: NCT00107198.