tbuckley/cabot-search huggingface dataset:
Updated overall survival (OS) for BRF113220, a phase 1-2 study of dabrafenib (D) alone versus combined dabrafenib and trametinib (D+T) in pts with <i>BRAF</i> V600 mutation-positive (+) metastatic melanoma (MM).
Authors: Keith Flaherty, Adil Daud, Jeffrey S. Weber, Jeffrey Alan Sosman, Kevin Kim, Rene Gonzalez, Omid Hamid, Jeffrey R. Infante, Jonathan S. Cebon, Lynn Mara Schuchter, Georgina V. Long, Alain Patrick Algazi, Ragini Reiney Kudchadkar, Igor Puzanov, Donald P. Lawrence, Amy S. Kline, Elizabeth Ann Cunningham, Peng Sun, Kiran Patel, Richard Kefford
Journal: Journal of Clinical Oncology (2014)

9010^ Background: D, a selective BRAF inhibitor, and T, a reversible, highly selective allosteric inhibitor of MEK1/2, are approved monotherapies, and an FDA approved combination therapy for BRAFV600mutation + MM. Methods: Safety and efficacy of D+T were evaluated in this Phase 1-2 study. BRAFV600E/Kmutation + MM pts naive to BRAFi and MEKi were enrolled. Part B (Ph 1, n=77 BRAF naive) pts enrolled into escalating cohorts of D mg BID + T mg QD – 75/1, 150/1, 150/1.5 and 150/2 respectively. Part C (Ph 2, n=162) pts were randomized 1:1:1 to D 150 mono, 150/1 and 150/2. Cross-over from D mono to 150/2 was allowed post progression of disease (PD). Primary endpoints were progression free survival (PFS), response rate (RR), duration of response (DoR), and safety; secondary endpoints were OS and PK. Results: Updated OS for pts in Parts B and C with median follow-up of 28 and 24 months (mo) presented in Table 1.In Part C, median OS for 150/2 pts is 23.8 mo (HR=0.73 vs. D mono, p-value=0.24); 18-mo OS rate is 63%, reflective of paradigm shifting improvements in OS in this population. OS for D mono is confounded by cross-over to 150/2; 45 (83%) pts crossed over at time of analysis. In 150/1 and 150/2, 43 (80%) and 24 (44%) continued to receive D+T beyond RECIST PD. Subsequent systemic therapies were similar across arms; 38 (23%) pts received immune checkpoint inhibitors (19% ipilimumab and 8% PD-1/PD-L1 13), and 19 (12%) received vemurafenib. Conclusions: Updated median OS is 23.8 mo for 150/2. Contribution of treatment beyond PD or post-treatment therapy is unknown. Follow-up continues; updated OS and safety data analysis will be performed in the final analysis after 30 mo follow-up or 75% events. Clinical trial information: NCT01072175. Treatment Number of deaths n (%) Med OS, mo (95% CI) Hazard ratio (95% CI) p-value 12-mo OS rate (%) 18-mo OS rate (%) Part B 150/2 (N=24) 8 (33) NR (12.9, NR) NA 73 67 Part C D mono (N=54) 31 (57) 20.2 (14.5, 25.9) NA 70 56 150/1 (N=54) 27 (50) 18.7 (13.7, NR) 0.96 (0.57, 1.60) 0.8683 69 51 150/2 (N=54) 25 (46) 23.8 (17.5, NR) 0.73 (0.43, 1.24) 0.2436 80 63 Abbreviations: NR, not reached; NA, not applicable.
SGN-30 (Anti-CD30 Monoclonal Antibody) Is Active and Well Tolerated in Patients with Refractory or Recurrent Systemic Anaplastic Large Cell Lymphoma.
Authors: Andres Forero-Torres, Steven Bernstein, Ajay Gopal, Francine Foss, John Leonard, Joseph Rosenblatt, Nancy Bartlett, Anas Younes, David Fisher, Bruce Cheson, Matthew Carabasi, Gregory Bociek, Bruce Hart, Michael McDonald
Journal: Blood (2004)
Evaluation of the DAS28 at week 14 or week 22 correlates best with long term attrition to infliximab therapy in rheumatoid arthritis patients
Authors: B. Vander Cruyssen, Patrick Durez, S. Van Looy, B. Wijns, Rene Westhovens, F. Van den Bosch, H. Mielants, L. De Clerck, A. Peretz, Michel Malaise, L. Verbruggen, N. Vastesaeger, A. Geldhof, L. Boullart, F. De Keyser
Journal: Annals of the Rheumatic Diseases (2006)
Patterns of metastasis, response to treatment and survival in young patients with advanced non small cell lung cancer (NSCLC)
Authors: A. Addeo, V. Dongiovanni, N. Birocco, D. Dongiovanni, C. Fissore, L. Buffoni, G. Numico, O. Bertetto
Journal: Journal of Clinical Oncology (2004)

7343 Background: We analysed our cancer registry to determine the clinicopathologic characteristics, response to treatment and survival rates of NSCLC patients under 50 years of age at diagnosis. Methods:From 1997 to 2003 in our oncological centre we treated 47 patients under 50 years of age at diagnosis. Pts characteristics: male/female, 29/18; 9 pts were <40 years old; stage IIIA, IIIB, IV in 7/5/35; histological type: adenocarcinoma 18 pts (38%), NSCLC not specified 19 (40%). Radical treatment were applied only to 7 patients: chemoradiotherapy in 4 and chemosurgery in 3 pts. In pts with stage IV disease 46% had brain mts at the diagnosis, 34% bone mts, 29% liver mts, 23% adrenal mts and 50% presented multiple mts sites at diagnosis. In three pts the diagnosis was an incidental finding, the symptoms-diagnosis delay was < 1 month in 17 patients, 1–3 months in 9 pts and > 4 months in 18 pts. All patients were treated with first line chemotherapy: at the beginning of treatment ECOG-PS was 0/1/2 in 8/35/4; platinum-based doublets were administered in 90% of the patients. Results: in 40 pts evaluable for response we obtained 1 RC and 15 RP with ORR 40%; SD and PD were observed in 23% and 37%, respectively; (ORR intention-to-treat analysis 34%). Five pts progressed with brain metastasis and 2 with leptomeningeal carcinomatosis (49% of pts presented brain involvement during the clinical course). Median time to progression and survival were 2.8 and 10 months, respectively. Second-line chemotherapy was administered to 23 pts (49%): 14 pts were treated with taxanes. Fifteen pts were evaluable for response after second-line CT: we observed 3 PR (20%), 1 SD and 11 PD. Conclusions: Patients younger than 50 years with advanced/metastatic disease present data of response to chemotherapy, time to progression and survival comparable to older patients. In these patients brain and bone involvement was more frequent than expected. No significant financial relationships to disclose.
Acute myeloid leukemia (AML) in older women after adjuvant breast cancer therapy
Authors: D. A. Patt, Z. Duan, G. Hortobagyi, S. H. Giordano
Journal: Journal of Clinical Oncology (2006)

560 Background: Adjuvant chemotherapy for breast cancer is associated with the development of secondary AML, but this risk in an older population has not been previously quantified. Methods: We queried data from the Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database for women who were diagnosed with nonmetastatic breast cancer from 1992–1999. We compared the risk of AML in patients with and without adjuvant chemotherapy (C), and by differing C regimens. The primary endpoint was a claim with an inpatient or outpatient diagnosis of AML (ICD-09 codes 205–208). Risk of AML was estimated using the method of Kaplan-Meier. Cox proportional hazards models were used to determine factors independently associated with AML. Results: 36,904 patients were included in this observational study, 4,572 who had received adjuvant C and 32,332 who had not. The median patient age was 75.3 (66.0–103.3). The median follow up was 63 months (13–132). Patients who received C were significantly younger, had more advanced stage disease, and had lower comorbidity scores (p&lt;0.001). The unadjusted risk of developing AML at 10 years after any adjuvant C for breast cancer was 1.6% versus 1.1% for women who had not received C. The adjusted HR for AML with adjuvant C was 1.72 (1.16–2.54) compared to women who did not receive C. HR for radiation was 1.21 (0.86–1.70). HR was higher with increasing age but p&gt;0.05. An analysis was performed among women who received C. When compared to other C regimens, anthracycline-based therapy (A) conveyed a significantly higher hazard for AML HR 2.17 (1.08–4.38), while patients who received A plus taxanes (T) did not have a significant increase in risk HR1.29 (0.44–3.82) nor did patients who received T with some other C HR 1.50 (0.34–6.67). Another significant independent predictor of AML included GCSF use HR 2.21 (1.14–4.25). In addition, increasing A dose was associated with higher risk of AML (p&lt;0.05). Conclusions: There is a small but real increase in AML after adjuvant chemotherapy for breast cancer in older women. The risk appears to be highest from A-based regimens, most of which also contained cyclophosphamide, and may be dose-dependent. T do not appear to increase risk. The role of GCSF should be further explored. No significant financial relationships to disclose.
Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) as a predictor of response in head and neck squamous cell carcinoma (HNSCC)
Authors: A. Dave, M. Fury, N. Lee, H. Stambuk, Y. Wang, S. Karimi, D. Pfister, J. Koutcher
Journal: Journal of Clinical Oncology (2007)

6007 Background: We wish to assess on a preliminary basis whether pretreatment DCE-MRI predicts response to chemoradiation in HNSCC. Methods: Tumor perfusion was assessed in 14 patients (median age, 56y; 13 M, 1 F; squamous cell cancer 13, poorly differentiated carcinoma 1; base of tongue 6; tonsil 6; larynx 1; nasopharynx 1) with nodal metastases (size &gt;1 cc for DCE-MRI; N1, 3; N2a, 2; N2b, 4; N2c, 4; N3, 1; Stage III, 3; Stage IVa, 10; Stage IVb, 1) prior to platin-based concurrent chemoradiation therapy. Data were acquired on a 1.5 Tesla clinical scanner with a standard MRI protocol using a clinical contrast agent (Gd-DTPA). The two compartment model analysis measured the rate constants of the contrast agent transfer between the lesion and plasma compartments (k ep ) and elimination by the plasma (k el ). Each patient was assigned a single MR imaging parameter of uptake slope and compartmental model (Ak ep ) on the basis of the histogram analysis of all individually fit tumor voxels. Histogram analysis calculated the amplitude (a), width (s), and median (μ) of the distribution from the fitting procedure. Overall response was determined approximately 2–5 months post treatment. Results: DCE-MRI data showed a rapid rise in the time intensity curves for viable appearing tumor, whereas muscle showed minimal signal enhancement. The mean Ak ep value was higher for complete responders (CR/near CR, n = 7) than for incomplete responders (ICR, n = 7; 3 partial response, 4 no response) (12.29/min±4.09 vs 7.11/min±2.51 [P = 0.04]. The preliminary histogram analysis for the slope showed that the width and median were able to differentiate between CR and ICR, P=0.039 and P=0.013 respectively, while amplitude was not significant (P=0.150). Conclusions: These preliminary data suggest that DCE-MRI may prove to be a useful predictor of response in HNSCC patients, and thus may enhance prognostication, patient selection, and treatment outcomes. No significant financial relationships to disclose.
Smad4 as a Therapeutic Target in Nup98-HoxA9-Induced Leukemia.
Authors: Ronan Quere, Goran Karlsson, Silja Andradottir, Marianne Rissler, Karin Olsson, Falk Hertwig, Kristian Reckzeh, Jorg Cammenga, Stefan Karlsson
Journal: Blood (2008)
Evaluating the use of cardiac biomarkers for early detection of chemotherapy induced cardiotoxicity: A pilot study in a minority population
Authors: A. Bahekar, P. D. Grewal, V. Monga, R. Bhuriya, J. Molnar, P. Khosla
Journal: Journal of Clinical Oncology (2009)

e20546 Background: Doxorubicin and trastuzumab are associated with characteristic Type I and Type II cardiomyopathy. As breast cancer survival improves and concern about long-term cardiotoxicity grows, we will need appropriate markers to detect cardiotoxicity before measurable myocardial systolic dysfuntion. Recent data and several guidelines suggest that Troponin-I and B-type natriuretic peptide (BNP) may serve as cardiac biomarkers for early detection of cardiotoxicity. This study seeks to evaluate feasibility and utility of these markers in an outpatient oncology clinic setting. Methods: As a quality care initiative in a high risk minority patient population for cardiac disease, 55 consecutive patients who received doxorubicin and/or trastuzumab for the treatment of breast cancer had serum Troponin-I and BNP measured prior to each dose of doxorubicin, and every three months on trastuzumab. All patients also had normal baseline left ventricular ejection fraction (≥ 50%) measured by MUGA scan. IRB approval was obtained and medical records were reviewed independently by two authors. Results: Of the 55 patients, two did not have adequate data; 58% of patients received dose dense doxorubicin; 15% of patients received trastuzumab. Significantly more number of patients had troponin-I rise as compared to BNP. Total 7 (13%) patients had abnormal LVEF by MUGA scan following chemotherapy. Five (71%) of these patients had rise in Troponin-I/BNP. Negative predictive value of biomarkers was 91%, with sensitivity of 71% and specificity of 44%. Conclusions: Use of standard cardiac biomarkers to detect early cardiotoxicity is feasible with a high negative predictive value for Troponin I and BNP in the first 90 days following chemotherapy with doxorubicin and/or trastuzumab. Patients with normal markers may not need intense cardiac monitoring. [Table: see text] [Table: see text]
Outcome of colon cancer patients with synchronous metastases
Authors: I. Sobhani, F. Roudot-Thoraval, F. Mesli, B. Landi, T. Aparicio, C. Louvet, G. DesGuetz, E. Mitry
Journal: Journal of Clinical Oncology (2009)

4029 Background: Metastatic colon cancer patients may undergo chemotherapy without colon surgery. However, the outcome of patients has not been evaluated and antiagiogenic agents can not be given. The aim of the present cohort study was to analyse factors influencing patients’ survival. Methods: Consecutive patients [N=228, mean age (sd) 64 (12) yrs, median follow-up 20 mths;84 females] treated in 6 teaching hospitals received chemotherapy for metastatic colonic cancer, either as the first step, or after surgery. Progressive free survival (PFS) was estimated using Kaplan-Meïer method. Factors associated with PFS were tested by means of Log rank test and results are presented in terms of medians of survival (95% CI). Factors independently related to PFS were tested using a Cox model and results are presented as hazard ratio. Results: 105 patients with colon cancer and synchronous metastatsis underwent colon surgery prior to chemotherapy (68 males, mean age 64 yrs) when 123 patients were treated first by chemotherapy ± biotherapy (76 males, mean age 63 yrs). By univariate analysis, following factors were significantly associated with PFS: surgery first 25.5 (18.6 - 32.5) vs chemotherapy first 18.3 (14.7 - 21.9) mths p = 0.006; curative surgery: yes 35.7 (29.6 - 41.8) vs no 18.4 (15.6 - 21.2) mths p &lt; 0.001; tumour histological differentiation : no : 13.4 (6.2 - 20.6) vs well : 24.7 (20.4 - 29.1) mths p&lt;0.001; synchronous metastases: liver only 25.5 (20.5 - 30.6) vs peritonea&amp;nodes : 18.4 (10.6 - 26.1) vs pulmonary &amp; other sites : 16.5 (14.7 - 18.3) mths p &lt; 0.0001; need for colonic stent: yes 16.4 (9.3 - 23.5) vs no 23.9 (21.1 - 26.7) months p &lt; 0.0001; antiangiogenic drug: yes 36.6 (28.7 - 44.5) vs no : 20.7 (18.3 - 23.1) p = 0.033. After Cox multivariate analysis five independent factors were found to be associated with PFS. Conclusions: Colon surgery before chemotherapy plus bevacizumab appears to be the more appropriate choice, and associated with longer PFS, especially for those patients with well differentiated tumours and synchronous liver metastases. [Table: see text] No significant financial relationships to disclose.
A phase II study of oxaliplatin reintroduction in patients pretreated with oxaliplatin and irinotecan for advanced colorectal cancer (RE-OPEN study).
Authors: Mitsukuni Suenaga, Nobuyuki Mizunuma, Satoshi Matsusaka, Eiji Shinozaki, Masato Ozaka, Mariko Ogura, Keisho Chin, Toshiharu Yamaguchi
Journal: Journal of Clinical Oncology (2015)

758 Background: Re-introduction of oxaliplatin (L-OHP) for patients with metastatic colorectal cancer (mCRC) refractory to standard chemotherapy regimens including L-OHP, irinotecan (CPT-11), and fluorouracil was thought to be effective approach. We performed a single arm, open-label phase II study (UMIN ID: 000004884), and the reported results of interim analysis were promising. Methods: Patients with prior chemotherapy including L-OHP and CPT-11 achieved tumor response or stable disease during prior L-OHP based therapy, and 6 months or over from confirmed progression disease during previous L-OHP based therapy was eligible for this study. Patients received FOLFOX regimens every two weeks. Primary endpoint was disease control rate (DCR) after 12 weeks of treatment start. Tumor response was evaluated by RECIST v1.1, and DCR was defined as complete response (CR), partial response (PR) or stable disease. This trial followed a Simon’s two-stage minimax design. Assuming the expected and threshold DCR after 12 weeks of treatment start would be 40% and 20%, 33 patients (18 in Step I and 15 in Step II) were required with a one sided α-level of 5% and a power of 80%. Results: Between February 2011 and August 2013, 33 patients were enrolled in this study. Characteristics of patients were as follows (n=33): median age of 62 years (35-77); male/female: 19/14; ECOG PS0: 84.8%; and colon/rectum: 14/19. All patients received mFOLFOX6 regimen. The DCR after 12 weeks of treatment start was 39.4% (95% CI: 21.8-57.0%), and the primary endpoint was met. The response Rate (CR or PR) was 6.1%. The median number of courses of chemotherapy was five, and the median total dose of L-OHP was 366.9 mg/m 2 . The median progression free survival was 98 days and the median overall survival was 300 days. The incidence of allergic reaction was 24.4% and peripheral neuropathy was 90.9%, graded as mild to moderate events. There were no other severe adverse events and treatment related deaths. Conclusions: Reintroduction of L-OHP was effective and could be a new salvage option for patients with mCRC refractory to previous L-OHP based therapy. Clinical trial information: 000004884.
Abstract 10647: Common Familial Effects on Ischemic Stroke and Myocardial Infarction: A Swedish National Cohort Study
Authors: Katherine Kasiman, Cecilia Lundholm, Sven Sandin, Ninoa Malki, Par Sparen, Erik Ingelsson
Journal: Circulation (2012)

Introduction: Recent genome-wide association analyses suggest some overlap of genetic determinants of ischemic stroke (IS) and myocardial infarction (MI). This study aimed to assess shared familial...
Lung cancer in the pre- and post-highly active antiretroviral therapy (HAART) era: A study on 61 HIV-infected patients
Authors: A. Bearz, M. Spina, R. Talamini, A. Lleshi, S. Spazzapan, E. Vaccher, M. Berretta, U. Tirelli
Journal: Journal of Clinical Oncology (2004)

7180 Background: Mortality rates for HIV-related illnesses are decreased since the introduction of HAART. Lung cancer, one of the most frequent non-AIDS-defining tumors, showed aggressive clinical course in the pre-HAART era. To assess the influence of HAART on HIV-related lung cancer, we retrospectively analyzed 61 cases collected on behalf of GICAT (Italian Cooperative Group on AIDS and Tumors) Methods: Clinical data of HIV-infected pts with lung cancer have been collected since 1986. Comparison of presenting features and outcome are made between cases diagnosed pre- and post-HAART era (≤ 1996 and ≥ 1997). Results: We analyzed data from 61 HIV-positive pts, M:F=53:8, with lung cancer diagnosed before and after HAART introduction in 34 (54%) and 27 (44%) pts respectively. Median age is 41 years (yrs), 39 and 45 yrs in the pre- and post-HAART group respectively. All the patients were smokers. Main risk group was IVD in 63%. NSCLC was predominant, 25 (76%) and 25 pts (93%), pre- and post-HAART respectively; adenoca was the main histology, 12 (48%) and 13 (48%) pts. III and IV stages were predominant, 24 (72%) and 22 ( 81%) pts respectively. 8 (24%) and 1 (4%) pts received no treatment, for poor PS in pre- and post-HAART setting; chemotherapy was administered in 16 (48%) and 21 pts (78%), p=0,04.Overall survival (OS) in post-HAART is significantly better than in pre-HAART group, 7 and 3,8 months respectively (p=0,008); by lung cancer, median OS is better for post-HAART than pre-HAART pts (p=0,02), 7 and 4,1 months respectively; by infection, there was no difference between the two groups. Conclusion: HIV pts with lung cancer, despite an homogeneous advanced presenting feature, had a better OS post-HAART; moreover post-HAART pts got significantly more chemotherapy. In our opinion their better survival is due to a protective effect of HAART therapy and chemotherapy. Our data suggest that chemotherapy can be safely administered and significantly improve OS in HIV infected pts with lung cancer; we strongly suggest treatment for HIV lung cancer pts both by HAART and chemotherapy. Supported by ISS and AIRC grants. No significant financial relationships to disclose.
A phase I dose-escalation study of XL147 (SAR245408), a PI3K inhibitor administered orally to patients (pts) with advanced malignancies.
Authors: G. Edelman, C. Bedell, G. Shapiro, S. S. Pandya, E. L. Kwak, C. Scheffold, L. T. Nguyen, A. Laird, J. Baselga, J. Rodon
Journal: Journal of Clinical Oncology (2010)

3004 Background: XL147 is a selective inhibitor of class I PI3K isoforms. In preclinical cancer models, XL147 is cytostatic or cytoreductive as monotherapy and enhances the efficacy of targeted agents and chemotherapeutics. This open label, phase I dose escalation study assesses the safety, pharmacokinetics, pharmacodynamics and activity of XL147 in pts with advanced solid tumors and lymphoma. Methods: Using a standard 3 + 3 design, pts with solid tumors receive once daily XL147 on days 1-21 (21/7) or as a continuous daily dose (CDD) in 28-day cycles. Cycle 1 safety data determine dose-limiting toxicities (DLTs). Disease assessments occur every 8 weeks. The potential utility of pan-Class I PI3K inhibition in lymphoma pts will be explored. Results: 68 solid tumor pts have been treated: 41 on 21/7, 21 on CDD using capsules, and 6 on CDD using tablets. The MTD for 21/7 and preliminary MTD for CDD was 600 mg; MTD expansion in NSCLC and other solid tumor pts at 600 mg XL147 CDD is ongoing. Drug-related skin rash was reported in 12% of pts (both schedules) including 4% of pts with grade 3 events. DLTs on the 21/7 schedule were grade 3 rash; no DLTs have occurred on the CDD schedule. XL147-related SAEs included grade 4 arterial thrombosis and grade 3 rash (one pt each). XL147 plasma exposure on the CDD schedule (capsules) increased with dose from 100 to 400 mg and was similar for the 400 and 600 mg doses. Exposure was consistent between the CDD capsule and 21/7 schedules. Mean t1/2, z at steady state was 4-6 days. XL147 exposure for a 200 mg CDD tablet was in the range of that for the 400 and 600 mg capsule doses. XL147 reduced PI3K pathway signaling and phosphorylation of MEK and ERK in tumor tissues exhibiting diverse molecular alterations, with associated reductions in Ki67 and increases in apoptosis. One NSCLC pt (225 mg dose, 21/7) had a confirmed PR with a 33% reduction in the target lesion. Thirteen pts continued on treatment ≥ 16 weeks, with nine pts on treatment ≥ 24 weeks. Conclusions: XL147 was generally well tolerated up to 600 mg 21/7 and CDD. The most common drug-related toxicity was skin rash. Inhibition of PI3K and ERK pathway signaling has been demonstrated in solid tumors, and prolonged stable disease has been observed. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Exelixis Exelixis Exelixis Exelixis