tbuckley/cabot-search huggingface dataset:
A phase 1b/2 study of INCB039110 + nab-paclitaxel (N) and gemcitabine (G) in patients (pts) with advanced solid tumors and pancreatic cancer (PC).
Authors: Gregory Lawrence Beatty, Safi Shahda, J. Thaddeus Beck, Nikhil Premparkash Uppal, Steven J. Cohen, Ross C. Donehower, A. Eli Gabayan, Albert Assad, Julie C. Switzky, Huiling Zhen, Daniel D. Von Hoff
Journal: Journal of Clinical Oncology (2017)

362 Background: JAK-STAT activity has been associated with malignant cell proliferation and production of proinflammatory cytokines involved in cancer progression. INCB039110 is a potent and selective inhibitor of JAK1. Methods: This was a 2-part phase 1b/2 open-label study evaluating INCB039110 (300 or 400 mg QD) in combination with N and G in pts with advanced or metastatic solid tumors (Part 1 [P1], dose optimization phase) and pts with advanced or metastatic PC who had not received prior chemotherapy (Part 2 [P2] and 2A [P2A]). Pts in P2 received the MTD established in P1: INCB039110 (300 mg QD) + N (125 mg/m 2 day [d] 1, 8, 15) + G (1000 mg/m 2 d 1, 8, 15), 28-d cycle. For exploratory purposes, pts in P2A underwent a 7-d induction phase with INCB039110 (200 mg QD) before receiving INCB039110 (200 mg QD) + N (125 mg/m 2 d 1, 8, 15) + G (1000 mg/m 2 d 1, 8, 15). The primary objective was to evaluate safety/tolerability. Results: 55 pts were enrolled (27 P1, 20 P2, and 8 P2A). Most patients had advanced PC (n = 46). Median age was 65 (P1), 67 (P2), and 66 years (P2A). Prior therapy: 67% in P1, 30% in P2, and 0% in P2A. The most common reasons for treatment discontinuation were adverse events (AEs; 41% P1, 20% P2, 38% P2A), disease progression (37% P1, 45% P2, 0% P2A), and study termination by the sponsor (0% P1, 0% P2, 38% P2A). Median treatment durations were 84 d (P1), 121 d (P2), and 47 d (P2A). The most common non-hematologic AEs (all grades) were fatigue (59% P1, 75% P2, 88% P2A), nausea (41% P1, 50% P2, 38% P2A), pyrexia (37% P1, 40% P2, 13% P2A), and peripheral edema (30% P1, 50% P2, 25% P2A), with few grade 3 or 4 non-hematologic AEs. The most common grade 3 or 4 hematologic AEs (laboratory values) were neutropenia (33% P1, 60% P2, 13% P2A), lymphopenia (30% P1, 30% P2, 13% P2A), and leukopenia (30% P1, 45% P2, 0% P2A). The most common serious AEs occurring in ≥ 3 pts were pneumonia (n = 4 P1, n = 2 P2, n = 0 P2A) and anemia (n = 3 P1, n = 2 P2, n = 2 P2A). Among evaluable patients, ORR (all PRs) and DCR were 27% (13/48) and 75% (36/48), respectively. Responses were seen across INCB039110 doses. Conclusions: INCB039110 + N/G showed an acceptable safety profile in pts with advanced PC, with the combination demonstrating clinical activity. Clinical trial information: NCT01858883.
Efficacy and safety of weekly oral vinorelbine (NVBO) as single agent in first- or second-line metastatic breast cancer (MBC).
Authors: Serafin Morales, Isabel Blancas, Maria Luisa Gonzalvez, Agust Barnadas, Nieves Diaz, Sonia Servitja, Sonia del Barco, Mireia Margeli, Iciar Garcia Carbonero, Ruth Alvarez, Maria Helena Lopez de Ceballos, Francisco Javier Perez, Antonio Llombart Cussac
Journal: Journal of Clinical Oncology (2012)

e11545 Background: NVBO has shown high activity and good safety profile when given as single agent chemotherapy (CT) for MBC. Oral CT formulations allow maintenance of quality of live and minimal interference with a normal lifestyle. Methods: Main inclusion criteria for this retrospective study were: Histologically or citologically confirmed MBC, no more than 1 prior CT line for MBC; prior (neo)adjuvant CT, hormonetherapy or radiotherapy allowed; adequate bone marrow, kidney and liver function. The study protocol was approved by an ethics committee. Data was collected from patients (p) treated between Apr/2006 and Dec/2010 with NVBO 60 mg/m 2 weekly until progression or unacceptable toxicity. 70 patients fulfilled the inclusion criteria. Patient’s characteristics were: Median age, 65 years (range 38-82); &gt;75 years old, 20%; ECOG PS 0-1 in 91% p and PS 2 in 9%; ER+ &amp;/or PR+, 41 p (59%); &gt;2 metastatic sites in 61%; prior (neo)adjuvant CT in 48 p (69%); prior hormonotherapy, 44 p (63%). Measurable disease in 68 p (97%). 1 p received trastuzumab concomitantly. Results: Median number of administrations (a) 11 (range 2-36). 1st/2nd line: 41%/59%. We analyzed 923 a. Dose delayed or reduced due to hematological toxicity in 2.7% a, related non-hematological toxicity in 0.3% a. Dose was reduced in 1% a. Hematological toxicities (%a): neutropenia grade (g) 3, 0.8%; febrile neutropenia 1 p who died due to septic shock after 9 a. Non-hematological toxicities (%a): pain g 3-4, 0.5%; constipation g 3-4, 0.3%; ileus paraliticus g 3, 0.1%; infection g 3, 0.1%; nausea/vomiting g4, 0.1% . 68 p were evaluable for response. 1 CR (1.5%), 19 PR (27.9%) and 16 SD (23.5%) were reported. Objective response (OR) rate 29.4% [CI 95%: 19%-41.7%]. Median progression free survival 4 m [CI 95%, 2.3-5.8]. Median survival has not been reached at the time of analysis. Conclusions: Our findings confirm the consistently produced clinically meaningful efficacy of single agent NVBO for MBC. We observed a favorable safety profile with a particular low incidence of myelosupression and alopecia. We consider that oral vinorelbine is a suitable 1st or 2nd-line treatment for convenient administration in an outpatient environment in selected p with MBC.
Overall survival in patients with advanced non-small cell lung cancer harboring concomitant <i>EGFR</i> mutations and <i>ALK</i> rearrangements: A cohort study.
Authors: Qing Zhou, Jinji Yang, Xuchao Zhang, Huajun Chen, Jian Su, Hai-Yan Tu, Hong-Hong Yan, Zhen Wang, Chongrui Xu, Yisheng Huang, Ben-Yuan Jiang, Bin-Chao Wang, Xiao-Yan Bai, Yi-Long Wu
Journal: Journal of Clinical Oncology (2014)

e19010 Background: Concomitant epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements define a rare molecular subtype of non-small-cell lung cancer (NSCLC). Objective response and progression-free survival (PFS) were investigated in advanced patients with such coalterations treated with EGFR tyrosine kinase inhibitors (TKIs) or ALK inhibitor crizotinib. To assess whether such genetic coalterations affect overall survival (OS) in these patients, we did a cohort study comparing survival outcomes in advanced patients with such coalterations, EGFR mutations and ALK rearrangements during the same time period. Methods: We examined OS in 11 patients with advanced, EGFR/ALK-coexisting NSCLC who received EGFR TKI, crizotinib or both of them sequentially from August 2009 to July 2011. For comparators, we identified 23 ALK-positive patients receiving second or further-line crizotinib from the two trials PROFILE 1005 and 1007, and 84 EGFR-mutant patients receiving first-line EGFR TKIs gefitinib and erlotinib. OS was calculated from first-line therapy. Results: Among 11 cases of advanced EGFR/ALK-coexisting NSCLC, 10 received first-line EGFR TKIs, and only one received first-line chemotherapy followed by second-line crizotinib and third-line gefitinib. Response rate of first-line EGFR TKIs was 80% (8/10) for EGFR/ALK-coexisting patients and 65.5% (55/84) for EGFR-mutant patients respectively, p = 0.570; median PFS, 11.2 v 13.2 months, Hazard ratio (HR) = 0.89, 95% CI 0.46~1.73, p = 0.73. Response rate of second or further-line crizotinib was 20% (2/5) for EGFR/ALK-coexisting patients and 73.9% (17/23) for ALK-positive patients respectively, p = 0.290; median PFS, 1.9 v 7.0 months, HR = 0.40, 95% CI 0.15~1.11, p = 0.07. Median OSs were 20.8, 24.0 and 18.8 months in EGFR-mutant, ALK-positive and EGFR/ALK-coexisting patients respectively, p= 0.24. Conclusions: OS in advanced NSCLC patients with concomitant EGFR mutations and ALK rearrangements is similar to that in those harboring either EGFR mutations or ALK rearrangements.
Randomized phase II trial to evaluate the safety and efficacy of neoadjuvant cisplatin in combination with taxanes-anthracyclines vs taxanes-anthracyclines alone in locally advanced triple negative breast cancer.
Authors: Maria Cristina Aguilar Martinez, Claudia Arce-Salinas, Alberto Alvarado-Miranda, Fernando Lara-Medina, Diana flores-Diaz, Juan Antonio Matus, Enrique Bargallo-Rocha, Robin Shaw-Dulin, Hector Maldonado, Leticia Mendoza-Galindo, Victor Perez-Sanchez
Journal: Journal of Clinical Oncology (2015)

e12024 Background: Triple negative breast cancer in our center represents 21% of all breast cancer cases. In these group of patients, its been suggested that cisplatin could improve breast cancer outcomes. The aim of this study was to evaluate the pathologic complete response (pCR) improvement with the addition of cisplatin to standard chemotherapy Methods: 80 patients were planned to be included, 61 patients were randomized in a 1:1 ratio. Standard group (A) received weekly paclitaxel 80 mg/m2 by 12, followed to 5FU, doxorubicin and cyclophosphamide 500/50/500 mg/m2 every 3 weeks times 4. Experimental group (B) received cisplatin 30 mg/m2 plus weekly paclitaxel 80 mg/m2 by 12, followed to cisplatin 75 mg/m2 plus doxorubicin 50 mg/m2 every 3 weeks for 4 cycles, followed by surgery. pCR was defined by the absence of tumor cells in the breast and lymph nodes. Safety analysis was made with CTC NCI v4.0. Local ethics committee approved the protocol. This is an interim analysis. Results: 30 patients were included in experimental group and 31 in standard group. Median age at diagnosis was 47 years. Median tumor size was 6 cm in both groups. Clinical response was achieved in 58% experimental group y 40% standard group p = 0.158, pCR was achieved in 39.2% and 58.6% respectively p = 0.344. Side effects were more common in experimental arm including anemia, neutropenia, nausea, vomiting and nephropathy, all of with statistics significance. Conclusions: There is a trend to improve pCR by adding cisplatin to standard chemotherapy, however there is also more hematological and non-hematological toxicity. Cisplatin addition improves in 30% our goal, and it is comparable with other literature reports.
A controlled, nonrandomized clinical research on chemotherapy combined with re-endostatin for stage IIB ostosarcoma.
Authors: Hairong Xu, Bin Li, Zhen Huang, Qing Zhang, Xiaohui Niu
Journal: Journal of Clinical Oncology (2014)

10538 Background: The aim of this study was to investigate the efficacy and safety of chemotherapy combined with re-endostatin (endostar) against stage IIB ostosarcoma. Methods: Patient of stage IIB ostosarcoma enrolled in Beijing Jishuitan Hospital from January 2008 to April 2012 were divided into combined group and control group. The chemotherapy regimen was as follows: methotrexate 10 g/m2 iv d1, ifosfamide 3 g/m2 iv d1-d5, cisplatin 120 mg/m2 iv d1, doxorubicin 30 mg/m2 iv d1-d3. Based on the same chemotherapy, endostar was added in combined group (15 mg/m2 iv d1-d14, 21 days was a cycle, for 4 cycles). Results: A total of 388 patients were enrolled in this study, and 58 cases were excluded in the final analysis. A total of 330 patients could be evaluated, in which 272 cases were in control group and 58 in combined group. Patients were followed up 6-59 months with a median period of 20.2 months. In the control group, 1-, 2- and 3-year distant metastasis-free survival rates were 79%, 70% and 65%, respectively, while those of combined group were 93%, 86% and 77% (p = 0.045). In the control group, 1-, 2- and 3-years of progression-free survival rates were 76%, 66% and 60%, respectively, while those of combined group were 90%, 83% and 74% (p = 0.025). In the control group, 1-, 2- and 3-year overall survival rates were 94%, 84% and 79%, while those of combined group were 98%, 94% and 85% (p = 0.220). The side effects in two groups were mainly in grade 1-2, and the common grade 3-4 side effects were leucopenia, anemia, hepatic dysfunction, nausea and vomiting. There was no difference in side effects of the two groups. Conclusions: The combination of chemotherapy and endostar can significantly improve the distant metastasis-free survival and progression-free survival in osteosarcoma patients, with tolerable side effects, worthy of further study.
Impact of comprehensive geriatric assessment on the survival of elderly patients with advanced cancer: IEGAC Retrospective Study.
Authors: Elisabeth Carola, Florence Woerth, Emmanuelle Sarlon, Bruno Chauffert, Sanaa Hannat, Roxana Fournier, Kamel Ghomari, Isabelle bresson-Raynaud, Isabelle Leduc, Maya Roucout, Momar Diouf, Celine Coppin, Laetitia Covin, Malika Akhoudas
Journal: Journal of Clinical Oncology (2015)

e20520 Background: Comprehensive geriatric assessment (CGA) helps therapeutic decision, predicts chemotherapy toxicities and early deaths in elderly patients treated for advanced cancer. CGA, performed at the time of oncologic therapeutic decision (initial CGA), has been progressively implemented in the Picardie region since 2008. In order to evaluate the clinical impact of initial CGA on survival of elderly cancer patients, we launched a retrospective multicentric collaborative study (IEGAC). Methods: Data from patients aged of 75 years or older and who received first line chemotherapy for advanced breast, ovary or colorectal cancer, from 2008 to 2012 were collected. Two groups were defined based on the implementation (group A) or not (group B) of initial CGA. Primary endpoint was overall survival (OS) from start of chemotherapy until patient’s death or last contact. Survival was calculed using Kaplan Meier method, log rank test used to comparison. Survival curves were adjusted with propensity score method, Cox model was built to explore relationship between survival and main explanatory variables. Results: 60 patients were includedin group A and 78 in group B. Mean age was 81 years in group A and 79 in group B (p = 0.002). With a median follow up of 89.2 months [95%CI: 44.6-not reached] median OS was not significantly different between group A (24.3 months, [95%CI: 21.4-30.4]) and B (29.3 months, [95%CI: 19.2-34.5]), HR = 0.94 (95%CI:0.61-1.43, p = 0.77). There was no difference of median OS between patients aged under 80 and over with initial CGA (HR = 0.69,95%CI:0.32-1.49;P = 0.35) or not (HR = 0.93,95%CI:0.51-1.69;P = 0.81) Conclusions: In this retrospective study, initial CGA did not have any impact on median OS of elderly cancer patients treated with chemotherapy. These results could be explained by a lack of power or selection bias inherent of any retrospective study, but they more probably reflect a huge improvement in the management of chemotherapy.
The Lung Cancer Genomic Screening Project for Individualized Medicine in Japan (LC-SCRUM-Japan): Screening for <i>RET</i> and <i>ROS1</i> fusions in advanced <i>EGFR</i> mutation-negative nonsquamous lung cancer and development of molecular targeted therapy.
Authors: Kiyotaka Yoh, Shingo Matsumoto, Katsuya Tsuchihara, Takashi Kohno, Genichiro Ishii, Koji Tsuta, Makoto Nishio, Noboru Yamamoto, Haruyasu Murakami, Miyako Satouchi, Naoyuki Nogami, Takashi Seto, Shigeki Umemura, Seiji Niho, Hironobu Ohmatsu, Yuichiro Ohe, Takeharu Yamanaka, Koichi Goto
Journal: Journal of Clinical Oncology (2014)

8055 Background: EGFR mutations and ALK fusions have emerged as important oncogenic drivers in non–small cell lung cancer (NSCLC). RET and ROS1 fusions have identified as new drivers of lung adenocarcinomas and these fusions are reported to be promising druggable targets. However, these gene fusions are encountered rather rarely, that is observed in only 1-2% of all lung adenocarcinomas. Methods: This study was established in February 2013 as a new nationwide genomic screening project for developing individualized medicine of advanced NSCLC patients in Japan. Tumor samples of advanced EGFR mutation-negative non-squamous lung cancer patients were eligible for submission. The specimens were screened for RET, ROS1 and ALK fusions by RT-PCR and FISH methods. Results: As of January 22th in 2014, The LC-SCRUM-Japan is under way with the participation of 158 institutions in Japan, under aid from the public research fund of the Ministry of Health, Labour and Welfare of Japan. 507 patients were enrolled to this st...
How are cared surviving cancer patients? Results of an Italian national survey to medical oncologists (MO) about clinical and organizational features of follow-up (FU).
Authors: Gianmauro Numico, Carmine Pinto, Giovanni Ucci, Stefania Gori, Massimo Di Maio, Maurizio Cancian, Francesco De Lorenzo, Marco Venturini
Journal: Journal of Clinical Oncology (2012)

e19592 Background: The growing demand and the resources shortage are pushing toward more efficient models of survivorship care delivery. The interface between the MO, the specialists involved in FU and Primary Care Physicians (PCP) should be optimized. While the “oncology centered” model seems hardly sustainable, a “sequential” model (PCP FU after an arbitrarily defined period of specialist FU) is gaining acceptance. A proposed alternative is a “shared-cares” model that promotes the interaction between MO and PCP throughout the whole clinical history. AIOM established a working group with the aim of promoting improvements at the national level. A survey aimed at assessing attitudes and feelings of MO was considered preliminary to any further initiative. Methods: A 25-item questionnaire was sent to the mailing list of the Society, in a 2-months period during 2011. One MO per institution was asked to answer to the questions. The sections of the survey were the following: 1) organizational features of FU; 2) clinical features involving breast (BC) and colorectal cancer (CRC) FU; 3) feelings of MO about the different meanings of FU. Results: 91 MO of 160 institutions (57%) answered. A shared organization between specialists is reported in 71% for BC and 53% for CRC. However, a shared medical record is used in only 19% and 11% respectively. The ordinary communication between MO and PCP consists in the medical report released to the pt in 87% and in other instruments in 8%. 55% and 30% of the MO follow BC and CRC pts indefinitely. In case of discharge, a conclusive letter is sent to the PCP in 74%, while a survivorship care plan is delivered in only 9%. Only 6% and 14% of the MO feel that FU has an important role in reducing mortality or in improving recurrence detection in BC. These figures grow to 31% and 47% for CRC. The educational role of FU is considered important in 36% and 32% while the psychological role in 44% and 37% for BC and CRC respectively. Conclusions: Although efforts are made to include other specialists and PCP into survivorship care, MO tend to privilege the “oncology centered” model. National efforts are being encouraged to promote the diffusion of a “shared-cares” model.
Rapid Radiologic Progression of Silicosis
Authors: Kazuo Tsuchiya, Mikio Toyoshima, Norimichi Akiyama, Masato Kono, Yutaro Nakamura, Kazuhito Funai, Satoshi Baba, Haruhiko Sugimura, Hitomi Kanayama, Takafumi Suda
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
Competing risks of death in NCIC CTG MA.27 adjuvant exemestane versus anastrozole.
Authors: Judy-Anne W. Chapman, Lois E. Shepherd, James N. Ingle, Hyman Bernard Muss, Kathleen I. Pritchard, Karen A. Gelmon, Timothy Joseph Whelan, Catherine Elliott, Paul E. Goss
Journal: Journal of Clinical Oncology (2013)

564 Background: Our group previously examined if baseline patient/tumor characteristics, or prior treatment affected cause of death in MA.17, a placebo controlled extended adjuvant trial of the aromatase inhibitor (AI) letrozole. We now examine factor effects on all cause mortality in MA.27. Methods: MA.27 was an adjuvant phase III superiority trial of 5 yrs of exemestane vs anastrozole, in ER+ postmenopausal breast cancer accrued between 2003 and 2008; event free survival was similar. We examined by intention-to-treat, the multivariate time-to-breast cancer-specific (BrCa), cardiovascular (Cardio), and other causes (OT) of death with log-normal survival analysis adjusted by treatment and stratification factors (lymph node status, adjuvant chemotherapy, celecoxib, aspirin, and trastuzumab). We tested whether factors were associated with 1) all cause mortality, and if so, 2) cause-specific mortality. We also fit step-wise forward cause-specific adjusted models. Results: 7,576 women (median age 64.1 years; 5417 (71.5%) &lt;70 yrs and 2159 (28.5%) &gt;70 yrs) were enrolled and followed for a median of 4.1 yrs. The 432 deaths comprised: 187 (43.3%) BrCa, 66 (15.3%) Cardiovascular, and 179 (41.4%) OT MA.27 therapy was not associated with mortality (p=0.84). Five baseline factors were differentially associated with cause of death. Older age was associated with greater BrCa (p=0.03), Cardio (p&lt;0.001), and OT (p&lt;0.001) mortality. Pre-existing cardiovascular history led to worse Cardio mortality (p&lt;0.001). Worse ECOG performance status led to worse OT death (p&lt;0.001). T1 tumors were associated with less BrCa mortality (p&lt;0.001). PgR+ tumors were also associated with less BrCa mortality (p&lt;0.001). There were fewer BrCa deaths with Node –ve disease (p&lt;0.001), ER+ tumors (p=0.001) and without adjuvant chemotherapy (p=0.005); there was worse Cardio mortality (p=0.01) with receipt of trastuzumab; worse OT (p=0.03) for non-whites, and without adjuvant radiotherapy (p=0.003). Conclusions: 56.7% of deaths in MA.27 patients were non-breast cancer related. We showed baseline patient and tumor characteristics, and prior treatment differentially affected cause of death. Clinical trial information: NCT00066573.
Results of autologous transplants for lymphomas from a tertiary cancer center in India
Authors: N. Jeevangi, A. Joshi, M. Shah, S. Kannan, S. Gupta, R. Nair, N. Khattry
Journal: Journal of Clinical Oncology (2009)

7106 Background: Autologous stem cell transplanation is the standard of care for patients of relapsed and refractory non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL). We report the results of transplants in lymphomas from our center and role of possible prognostic factors. Methods: All 50 consecutive patients who underwent transplant for HL (70%) and NHL (30%) from August 1994- August 2008 were included in this retrospective study. Fifty eight percent of patients received BEAM (carmustine, etoposide, ara-c and melphalan), 30% LACE (lomustine, ara-c, cyclophosphamide and etoposide), 8% ICE (ifosfamide,carboplatin and etoposide) and 4% high dose melphalan (200mg/m 2 ) conditioning regimens. Seventy eight percent of patients received peripheral blood stem cells (PBSC), 8% bone marrow (BM) and 14% both PBSC and BM. Prognostic factors evaluated for progression free survival (PFS) were serum albumin level and body mass index (BMI) at the time of transplant, stage at diagnosis and source of stem cells, while for over all survival (OS), status of disease at transplant was also included. Results: The median time to transplant was 2.25 years from the time of diagnosis. The median age at transplant was 25 years. Seventy four percent of patients were male. At the time of transplant, thirty two percent were in complete remission (CR), 50% in partial remission (PR) and 18% had refractory disease (RD). The median serum albumin and BMI at the time of transplant were 4 g/dl and 22.5 kg/m 2 respectively. The best disease response rate was 86% (CR+PR) in patients evaluable for response. Thirteen patients relapsed at a median interval of 11 months post transplant. The cumulative probability of OS and progression free survival PFS at 5 years were 40% and 34% respectively for the whole group. Multivariate analysis using cox regression identified serum albumin greater than 4 g/dl and those receiving PBSC grafts as independently associated with improved OS and PFS. Conclusions: These data provide the first published report of outcomes of autologous transplants in lymphomas from India. Our data suggests that serum albumin level at the time of transplant and stem cell source are important prognostic factors for PFS and OS. No significant financial relationships to disclose.