Search

Your search keyword '"Separovic, R."' showing total 26 results
Start Over Author "Separovic, R."
26 results on '"Separovic, R."'

5. 45P Long-term efficacy of neratinib in HER2-positive early-stage breast cancer: Overall survival and central nervous system outcomes from the phase III ExteNET trial

Author

Chan, A., primary, Moy, B., additional, Mansi, J.L., additional, Gnant, M.I., additional, Barrios, C.H., additional, Separovic, R., additional, Guerrero-Zotano, A., additional, Gore, I., additional, Smith, J., additional, Bryce, R.P., additional, Xu, F., additional, Wong, A., additional, Martin, M., additional, and Holmes, F.A., additional

Published
2021
Full Text
View/download PDF

6. Overall survival of patients with left-sided metastatic colorectal cancer in real life: Experience from University Hospital for Tumors in Zagreb, Croatia

Author

Pavlovic M, Separovic R, Lepetic P, Tecic Vuger A, Vazdar Lj

Subjects
colorectal cancer, overall survival, Croatia
Abstract

Background: According to 2016 Eurostat cancer statistics, Croatia has the secondhighest standardised death rate for colorectal cancer (CRC) among the EU Member States. In light of that fact, we tried to analyse the reasons behind this bad result in our cohort of patients. Available real-world data suggest that median OS of patients with left-sided mCRC is 22 to 25 months. Overall, around 750 patients are treated each year due to mCRC in Croatia. Of that, 70-75% are left-sided tumors. We present survival results of patients treated for left- sided mCRC in our institution. Methods: We conducted retrospective analysis on a consecutive sample of all patients who started their treatment with chemotherapy dublet +/- biological agent between January 1st, 2016 and December 31st, 2017. OS was calculated from the start of induction therapy to the death of the patient. Kaplan-Meier curves were used to estimate median survival and survival rates. Results: A total of 112 patients were analysed. Median age was 62 (39-85), 60% of patients were men and 40% women. At the time of diagnosis, as much as 60% of patients were metastatic and 60% of patients had more than one metastatic site. Chemotherapy without a biological agent was used in 25% of patients. An irinotecanbased induction chemotherapy regimen was used in 81% of patients. Among patients with biological therapy, 66% received bevacizumab and 34% received an anti-EGFR drug. When analysing two-year follow-up outcomes, the median PFS for 1st-line treatment was 11 months ; 38% of patients who received 2nd-line treatment had a median PFS of 5 months and only 5% of those who received 3rd-line treatment had a median PFS of 5 months. Two-year OS rate was 50%. More than a quarter of patients are still on therapy (27%) and median duration of treatment is 32.5 months. Conclusion: To best of our knowledge, this is the first report of overall survival data of patients with mCRC in Croatia to date. The negative trend in OS could be partly determined by late diagnosis and the fact that as much as 60% of patients were highrisk patients with initially metastatic disease and high tumor burden. This suggests that perhaps more effort should be made to diagnose the disease in an earlier stage. The lack of multidisciplinarity in our institution probably has a major impact on our results.

Published
2020

10. Neratinib after trastuzumab (T)-based adjuvant therapy in early- stage HER2+ breast cancer (BC): 5-year analysis of the phase III ExteNET trial

Author

Martin Jimenez, M, Holmes, FA, Ejlertsen, B, Delaloge, S, Moy, B, Iwata, H, von Minckwitz, G, Chia, S, Mansi, J, Barrios, C, Gnant, M, Tomasevic, Z, Denduluri, N, Separovic, R, Kim, SB, Jakobsen, EH, Bryce, RP, Xu, F, Buyse, M, Chan, A, and Andre, Fabrice

Subjects
macromolecular substances, neratinib, trastuzumab, rani rak dojke, ExteNET studija
Abstract

1 y of neratinib after T-based adjuvant therapy significantly improves iDFS at 5 y in pts with early-stage HER2+ BC, with a long-term sustained effect. A protocol-specified subgroup analysis suggested greater benefit in HR+ pts. Overall survival data are not yet mature.

Published
2017

11. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial

Author

Martin, M, Holmes, F, Ejlertsen, B, Delaloge, S, Moy, B, Iwata, H, von Minckwitz, G, Chia, S, Mansi, J, Barrios, C, Gnant, M, Tomasevic, Z, Denduluri, N, Separovic, R, Gokmen, E, Bashford, A, Borrego, M, Kim, S, Jakobsen, E, Ciceniene, A, Inoue, K, Overkamp, F, Heijns, J, Armstrong, A, Link, J, Abraham, A, Bryce, J, Wong, A, Moran, S, Yao, B, Xu, F, Auerbach, A, Buyse, M, Chan, A, Bidoli, P, Holmes, FA, Chia, SKL, Barrios, CH, Borrego, MR, Kim, SB, Jakobsen, EH, Heijns, JB, Armstrong, AC, Link, JS, Bryce, JR, Martin, M, Holmes, F, Ejlertsen, B, Delaloge, S, Moy, B, Iwata, H, von Minckwitz, G, Chia, S, Mansi, J, Barrios, C, Gnant, M, Tomasevic, Z, Denduluri, N, Separovic, R, Gokmen, E, Bashford, A, Borrego, M, Kim, S, Jakobsen, E, Ciceniene, A, Inoue, K, Overkamp, F, Heijns, J, Armstrong, A, Link, J, Abraham, A, Bryce, J, Wong, A, Moran, S, Yao, B, Xu, F, Auerbach, A, Buyse, M, Chan, A, Bidoli, P, Holmes, FA, Chia, SKL, Barrios, CH, Borrego, MR, Kim, SB, Jakobsen, EH, Heijns, JB, Armstrong, AC, Link, JS, and Bryce, JR

Abstract

Background ExteNET showed that 1 year of neratinib, an irreversible pan-HER tyrosine kinase inhibitor, significantly improves 2-year invasive disease-free survival after trastuzumab-based adjuvant therapy in women with HER2-positive breast cancer. We report updated efficacy outcomes from a protocol-defined 5-year follow-up sensitivity analysis and long-term toxicity findings. Methods In this ongoing randomised, double-blind, placebo-controlled, phase 3 trial, eligible women aged 18 years or older (≥20 years in Japan) with stage 1–3c (modified to stage 2–3c in February, 2010) operable breast cancer, who had completed neoadjuvant and adjuvant chemotherapy plus trastuzumab with no evidence of disease recurrence or metastatic disease at study entry. Patients who were eligible patients were randomly assigned (1:1) via permuted blocks stratified according to hormone receptor status (hormone receptor-positive vs hormone receptor-negative), nodal status (0 vs 1–3 vs or ≥4 positive nodes), and trastuzumab adjuvant regimen (given sequentially vs concurrently with chemotherapy), then implemented centrally via an interactive voice and web-response system, to receive 1 year of oral neratinib 240 mg/day or matching placebo. Treatment was given continuously for 1 year, unless disease recurrence or new breast cancer, intolerable adverse events, or consent withdrawal occurred. Patients, investigators, and trial funder were masked to treatment allocation. The predefined endpoint of the 5-year analysis was invasive disease-free survival, analysed by intention to treat. ExteNET is registered with ClinicalTrials.gov, number NCT00878709, and is closed to new participants. Findings Between July 9, 2009, and Oct 24, 2011, 2840 eligible women with early HER2-positive breast cancer were recruited from community-based and academic institutions in 40 countries and randomly assigned to receive neratinib (n=1420) or placebo (n=1420). After a median follow-up of 5·2 years (IQR 2·1–5·3), patients

Published
2017

12. Neratinib after trastuzumab (T)-based adjuvant therapy in early-stage HER2+ breast cancer (BC): 5-year analysis of the phase III ExteNET trial

Author

Martin Jimenez, M., primary, Holmes, F.A., additional, Ejlertsen, B., additional, Delaloge, S., additional, Moy, B., additional, Iwata, H., additional, von Minckwitz, G., additional, Chia, S., additional, Mansi, J., additional, Barrios, C., additional, Gnant, M., additional, Tomasevic, Z., additional, Denduluri, N., additional, Separovic, R., additional, Kim, S-B., additional, Jakobsen, E.H., additional, Bryce, R.P., additional, Xu, F., additional, Buyse, M., additional, and Chan, A., additional

Published
2017
Full Text
View/download PDF

13. Risk factors for the occurrence and irreversibility of cardiotoxicity caused by trastuzumab therapy

Author

Gabric, I. D., Vazdar, L. J., Pintaric, H., Planinc, D., Mario Štefanović, Trbusic, M., Vinter, O., Jazvic, M., Soldic, Z., and Separovic, R.

Subjects
cardiotoxicity, trastuzumab, breast cancer, skin and connective tissue diseases
Abstract

Cardiotoxicity is the most important side effect of trastuzumab, humanized monoclonal antibody to the HER2 protein, in use for immunotherapy of breast cancer. It is mainly manifested as a reduction in left ventricular contractility without myocardial necrosis and the process is therefore mostly reversible. However, sometimes the disease can progress to irreversible dilated cardiomyopathy. So far, many risk factors explaining cardiotoxicity have been identified, but it is still unclear how to assess individual risk. Also, there are no defined factors that can predict irreversibility of the disease. Pts with D/D ACE genotype, tumor of the left breast and positive family history of cardiovascular disease have a higher risk of developing cardiotoxicity with trastuzumab therapy and should be treated as high risk pts. Trastuzumab induced cardiotoxicity ismore likely to be irreversible in pts with a more extensive decrease of the LVEF and a higher serum NT-proBNP level. The time between prior chemotherapy and administration of trastuzumab shorter than 30 days ismore often associated with irreversible cardiac impairment.

Published
2015

14. A Phase II Study of Trastuzumab Plus Capecitabine with or Without Pertuzumab for HER2-positive Metastatic Breast Cancer as Second-line Treatment (PHEREXA)

Author

Urruticoechea, A, Canney, P, Separovic, R, Bachelot, T, Efran, J, Canon, JL, Martinez del Prado, P, Barone, C, Mayne, M, and Munoz, M

Subjects
mental disorders, capecitabine, pertuzumab, trastuzumab, breast cancer, skin and connective tissue diseases, neoplasms
Abstract

Capecitabine in combination with trastuzumab is more efficacious than capecitabin alone as second-line treatment of patients with metastatic HER2-positive breast cancer

Published
2012

15. Trastuzumab plus capecitabine with or without pertuzumab in patients with HER-2 positive MBC whose disease has progressed during or following trastuzumab-based therapy for first-line metastatic disease: A multicenter, randomized, two-arm, phase II study (PHEREXA)

Author

Munoz-Mateu, M, Urruticoechea, A, Separovic, R, Erfán, J, Bachelot, TD, Canon, J, Kovalenko, N, Staroslawska, E, Pikó, B, Veyret, C, Pribylova, O, Ciule, DL, Ratnayake, J, Das, S, Mayne, K, and Ross, G

Subjects
capecitabin, trastuzumab, pertuzumab, breast cancer, skin and connective tissue diseases
Abstract

Background: Pertuzumab (P) is a promising new anti-HER2 antibody which has shown both activity and good tolerability when combined with trastuzumab (H) in patients with HER2-positive breast cancer. Capecitabine (X) in combination with H has been shown to be more efficacious than X alone as second-line treatment of patients with HER2-positive metastatic breast cancer (MBC). The PHEREXA study is designed to investigate the potential benefit of administering P and H combined with X in patients with HER2-positive MBC whose disease has progressed during or following H-based therapy for first- line MBC. Methods: In this multicenter, open-label, Phase II trial (NCT01026142), patients are randomized 1:1 to Arm A (H: 8 mg/kg loading dose followed by a 6 mg/kg maintenance dose ; X: 1250 mg/m2 twice daily for 14d q3w) or Arm B (H: 8 mg/kg loading dose followed by a 6 mg/kg maintenance dose ; X: 1000 mg/m2 twice daily for 14d ; P: 840 mg loading dose and 420 mg thereafter q3w). Enrolment began in January 2010 and 450 patients are to be recruited from ~130 sites in 19 countries. Eligible patients must have HER2-positive MBC (fluorescence or chromogenic in situ hybridization-positive and/or immunohistochemistry 3+), which has progressed during or following H-based therapy for first-line MBC, prior taxane, and left ventricular ejection fraction (LVEF) ≥50% at baseline. Exclusion criteria include prior treatment with X or P, concurrent immunotherapy or hormonal anticancer therapy, and history of LVEF decline to

Published
2011

16. CARIATIDE study: Evaluation of the impact of educational material on the compliance and persistence rates to adjuvant aromatase inhibitor (AI) medication for postmenopausal women with hormone sensitive early breast cancer

Author

Neven, P, Serin, D, Separovic, R, Ozaslan, C, and Tanner, M

Subjects
education, compliance, aromatase inhibitor, breast cancer
Abstract

In the absence of trial data regarding the optimum duration of AI therapy, this study indicates that over one-third (36%)of oncologist surveyed are using adjuvant AIs for more than 5 years. This practice is likely an extrapolation of data from the extended adjuvant setting. The majority of respondents prescribing initial AI therapy are most likely driven by reported data from large RCTs that demonstrated significanty greater benefit for AI therapy over tamoxifen.

Published
2009

19. Trastuzumab plus capecitabine with or without pertuzumab in patients with HER2-positive MBC whose disease has progressed during or following trastuzumab-based therapy for first-line metastatic disease: A multicenter, randomized, two-arm, phase II study (PHEREXA).

Author

Munoz-Mateu, M., primary, Urruticoechea, A., additional, Separovic, R., additional, Erfán, J., additional, Bachelot, T. D., additional, Canon, J., additional, Kovalenko, N., additional, Staroslawska, E., additional, Pikó, B., additional, Veyret, C., additional, Pribylova, O., additional, Ciule, D. L., additional, Ratnayake, J., additional, Das, S., additional, Mayne, K., additional, and Ross, G., additional

Published
2011
Full Text
View/download PDF

23. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial

Author

Miguel Martin, Frankie A Holmes, Bent Ejlertsen, Suzette Delaloge, Beverly Moy, Hiroji Iwata, Gunter von Minckwitz, Stephen K L Chia, Janine Mansi, Carlos H Barrios, Michael Gnant, Zorica Tomašević, Neelima Denduluri, Robert Šeparović, Erhan Gokmen, Anna Bashford, Manuel Ruiz Borrego, Sung-Bae Kim, Erik Hugger Jakobsen, Audrone Ciceniene, Kenichi Inoue, Friedrich Overkamp, Joan B Heijns, Anne C Armstrong, John S Link, Anil Abraham Joy, Richard Bryce, Alvin Wong, Susan Moran, Bin Yao, Feng Xu, Alan Auerbach, Marc Buyse, Arlene Chan, Vernon Harvey, Rudolf Tomek, Nicholas J. Robert, Ira Gore, John W. Smith, Norikazu Masuda, S. Di Sean Kendall, William Graydon Harker, Katarina Petrakova, Angel Guerrero Zotano, Amparo Ruiz Simon, Zora Neskovic Konstantinovic, Nicholas O. Iannotti, Pierfrancesco Tassone, Gladys I. Rodriguez, Noelia Jáñez Martinez, Carmen Crespo Massieu, Snezana Smickoska, Isil Somali, Ugur Yilmaz, Mirta Garcia Alonso, Adolfo Murias Rosales, Soeren Cold, Ann Soegaard Knoop, Debra Patt, Beth A. Hellerstedt, Serafin Morales Murillo, Ingrid A. Mayer, Julie Ann Means-Powell, Rina Hui, Francis M. Senecal, Richard Hendry De Boer, Zhenzhou Shen, Adam Andrzej Luczak, Joanna W.Y. Chui, Janice Wing-hang Tsang, Istvan Lang, Yoshiaki Rai, Yasuo Hozumi, Albert J. Ten Tije, Manish Bhandari, Cynthia R.C. Osborne, Shoichiro Ohtani, Kenji Higaki, Kenichi Watanabe, Kazunori Taguchi, Masato Takahashi, Sladjana Filipovic, Vincent L. Hansen, Vijayarama Phooshkooru Rao, Manish Gupta, Petar Petrov, Bruno Coudert, Zeljko Vojnovic, Zsofia Polya, Toshiko Miyaki, Naohito Yamamoto, Stephen Brincat, Krzysztof Lesniewski-Kmak, Ewa Chmielowska, Ruemu E. Birhiray, Marc L. Citron, Steven William Papish, William R. Berry, Sven Tyge Langkjer, José Angel Garcia Sáenz, Ana Maria Arance, Noa Efrat, Tomasz Sarosiek, Lukasz Grzeda, Yvonne Manalo, Julie C. Smith, Irfan Vaziri, Tabitha Healey, Yasmin Rahim, Cynthia Luk, Brian Dingle, Sandra Franco, Peter Grundtvig Sorensen, Anjana Anand, Sarah Khan, George Fountzilas, Kenjiro Aogi, Satoru Shimizu, Milada Mikulova, Stanislav Spanik, Robert A. Somer, Patrick J. Flynn, Jermaine Coward, Paul Mainwaring, Guy Jerusalem, Carine Segura-Ojezzar, Christelle Levy, Thierry Delozier, David Khayat, Robert E. Coleman, Martin J. Rolles, Robert Maisano, Mario Nardi, Yoshinori Ito, Perran Fulden Yumuk, Gul Basaran, Nazim Serdar Turhal, Mary J. Wilkinson, Nathan B. Green, Algis P. Sidrys, Sigrun Hallmeyer, Douglas J. Testori, Srikala Sridhar, Jose Chang, Qiang Sun, Carlos Jara-Sanchez, Xabier Rubio, Maria Lomas Garrido, Juan Rafael De La Haba Rodriguez, Antonia Perello Martorell, Antoni Avelia Mestre, Julio Rifa Ferrer, Sonia del Barco Berron, Zsuzsanna Nagy, Maki Tanaka, Young-Hyuck Im, Robert R. Carroll, Laura C. Dickerson, Joseph R. Mace, Ragene Rivera, Leonard M. Klein, Robert Ruxer, Sharon T. Wilks, Dusan Kotasek, Vasil Popov, Violina Taskova, Violetka Marinova-Venkova, Constanta Timcheva, Christine Desbiens, Jean-Pierre Ayoub, Debjani Grenier, Norbert Marschner, Hans Tesch, Hans-Joachim Lueck, Jan Janssen, Ingo Schwaner, Stine Wahlstrom, Eva Harder Brix, Susanne Vallentin, Dan Kristensen, Anna Andreeva, Vesna Glavicic, Isabel Calvo Plaza, Antonio Anton Torres, Corinne Veyret, Jean-Pierre Bergerat, Emmanuelle Bourbouloux, Wendy Ann Ella, Hafiz Algurafi, Anne Robinson, Seung Jin Kim, Tetsuya Taguchi, Elona Juozaityte, Stanley Madretsma, Sandra Radema, Malgorzata Czerniawska-Meier, Wojciech Rogowski, Maria Wagnerova, Donald A. Richards, Elizabeth Tan-Chiu, Asskikis Vasileios, Charles Arthur Henderson, Viran Roger Holden, Xiaojia Wang, Zhongsheng Tong, Junlan Yang, Manuel Enrique Gonzalez, Mahdi Rezai, John Hackmann, Eduardo Martinez de Dueñas, Begoña Bermejo de las Heras, Louis Marie Dourthe, Dorothee Chocteau-Bouju, Philippe Bougnoux, Stylianos Kakolyris, Haralabos Kalofonos, Dimitrios Pectasidis, Ting Ying Ng, Gabor Pajkos, Eva Ezer Somogyine, Giuseppe Tonini, Dario Giuffrida, Shintaro Takao, Makoto Ishitobi, Hideo Inaji, Yutaka Tokuda, Katarzyna Wozniak, Dan Lungulescu, Yen-Shen Lu, King-Jen Chang, Julian Hill, Christopher Charles Croot, Albert Dekker, Neil D. Belman, Miguel Conde, Richard A. Michaelson, Kathleen Kemmer, Stephen Chui, Shiuh-Wen Luoh, Kenneth Nahum, Andrew R. Greenspan, Joni C. Nichols, Carlos A. Encarnacion, Thomas M.J. Niederman, Theresa Lee, Roland Alexander, Robert Gordon, Antoanet Tomova, Daniel Rauch, Razvan Andrei Popescu, Gustavo Adolfo Rojas, Jaroslav Vanasek, Tanja Neunhoeffer, Jana Barinoff, Gerd Graffunder, Abenhardt Wolfgang, Peter Bojko, Bernhard Heinrich, Albert von der Assen, Bogovic Jurij Antonovic, Lene Adrian, Manuel Ramos Vazquez, Santiago Gonzalez Santiago, Veronique Dieras, Jill Mercia Bishop, Timothy John Perren, Ioannis Varthalitis, Dimitris Mavroudis, Vassilis Georgoulias, Louis W.C. Chow, Chung Cheung Thomas Yau, Raymond Hin-Suen Liang, Béla Pikó, Agnes Wéber, Bella Kaufman, Karen Drumea, Francesco Nuzzo, Andrea De Matteis, Giacomo Carteni, Eriko Tokunaga, Mayumi Ishida, Shinji Ohno, Nobuaki Sato, Katsumasa Kuroi, Reiki Nishimura, Junichiro Watanabe, Yoon Ji Choi, Kyong Hwa Park, Marek Wojtukiewicz, Jacek Jassem, Niklas Loman, Sercan Askoy, Mustafa Kadri Altundag, Pinar Saip, Muhammad Amjad Ali, James Lloyd Wade, Amy Jo Chien, Debra Brandt, Yelena Novik, Chirag Jani, Robert L. Rice, Yousuf A. R Gaffar, Mark R. Keaton, Rajesh Bajaj, Gretchen Kimmick, David Campbell, Theodore Turnquest, Sideras Lucas, Pierre Dube, Binghe Xu, Joerg Schilling, Klaus Apel, Peter Michael Vestlev, Brita Bjerregaard Jensen, Vera Haahr, Alvaro Rodriguez Lescure, Begona Grana Suarez, Cristina Saura Manich, Jean-Philippe Jacquin, Ahmed Samreen, Ion Boiangiu, Magdolna Dank, Cristina Falci, Antonio Jirillo, Saverio Cinieri, Takayuki Ueno, Fumiaki Sato, Hiroyasu Yamashiro, Tomoharu Sugie, Keun Seok Lee, Jung Sil Ro, In Hae Park, Anita Zarina Bustam, Malgorzata Suszko-Kazarnowicz, Artur Piktel, Krzysztof Krzemieniecki, Polizenia Georgeta Iorga, Yoon Sim Yap, Marian Kakalejcik, Alper Sevinc, Mustafa Ozguroglu, Shin-Cheh Chen, Richard H. Greenberg, Allan Daniel Eisemann, Robert Droder, M. Rashid Abbasi, Marina Vaysburd, Humberto Jose Caldera, Barbara Bacsik Haley, Erwin Robin, Roger C. Inhorn, David Hufnagel, Peter D. Kenyon, Ellen Spremulli, Paula Silverman, Sharad Jain, Robert Weigand, Jeroen Mebis, Tatyana Koynova, Bernard Lesperance, Jana Prausova, Claus-Henning Kohne, Andreas Schneeweiss, Christian Jackisch, Stefan Fuxius, Ricardo Cubedo Cervera, Ander Urruticoechea Ribate, Sonia Pernas Simon, Jose Valero Gallego, Angels Arcusa Lanza, Maria del Pilar Alvarez, Jesus Florian Gerico, Laurent Cany, Justin Stebbing, Dejan Labudovic, Damir Gugic, Damir Vrbanec, Fausto Roila, Sandro Barni, Paolo Bidoli, Hirofumi Mukai, Vanessa Bermudez, Alexandru Eniu, Barry C. Mirtsching, Emad Ibrahim, Joan Trey, Paul Francis Hergenroeder, Aftab Mahmood, Anneliese Gonzalez, Edward H. Kaplan, Stacy Ban, Dhimant Patel, Billy Clowney, Karen Hoelzer, Garry H. Schwartz, Mohamed Salkeni, Jame Abraham, Sunil Narula, Khaled Jabboury, Robert Scott Mocharnuk, Richard H. McDonough, David H. Sikes, Ronald H. Kawanchi, Larry Schlabach, Samuel Spence McCachren, Thomas M. Cosgriff, Luke Dreisbach, Angela DeMichele, Lawrence Pawl, Jennifer Lucas, Lowell C. Shinn, Nabiel Alkhouri, Manish Monga, Deborah L. Lindquist, Thomas C. Anderson, Humera Khurshid, Sabrina Witherby, Nicholette Erickson, Ann Traynor, Ron Bose, Timothy J. Pluard, Michael C. Jones, Sucharu Prakash, Fabio Volterra, Gerardo Capo, Lawrence E. Flaherty, Elaina Gartner, Said Baidas, Ian Okazaki, Bichlien Nguyen, Thomas Rakowski, Ira Oliff, Joseph W. Leach, Daniel Anderson, Kendra Kubiak, Michaela Tsai, Philippe Vroman, Ines Deleu, Willem Lybaert, Marleen Borms, Felix Couture, Jonathan J. Wilson, Gordon Hunt, David R. Holland, Walter Mingrone, Shusen Wang, Donggeng Liu, Zefei Jiang, Vera Benesova, Martin Smakal, Petra Garnolova, Anne-Sophie Vesper, Monika Neumann, Wolfgang Janni, Cornelia Liedtke, Dorothea Fischer, Eva-Maria Grischke, Dietmar Seeger, Volker Moebus, Anita Prechtl, Juan Carlos Camara Toral, Alfonso Sanchez Munoz, Sonia Gonzalez Jimenez, Javier Cassinello Espinosa, Beatriz Cirauqui, Mireia Margeli Vila, Norberto Batista Lopez, Jose Ignacio Chacon Lopez-Muniz, Miguel Angel de la Cruz Mora, Audrey Mailliez, Laurence Vanlemmens, Damien Pouessel, Marc Espie, John Conibear, Rebecca Roylance, Adrian Harnett, David Geffen, Enzo Maria Ruggeri, Teresa Gamucci, Cees J. Van Groeningen, Renata Banas, Necati Alkis, Ming-Feng Hou, Amy K. Krie, Nandagopal S. Vrindavanam, Orion M. Howard, Dennis Citrin, Mark S. Morginstin, Ajit Desai, Ines J. Sanchez, David Allen Nixon, Patrick G. Beatty, Kathryn Edmiston, Marilyn McLaughlin, Jonathan D. Eneman, Cynthia A. Lynch, Edward O'Brien, Justin A. Call, Keith S. Lanier, Alison Conlin, Donald J. Brooks, Kristi McIntyre, Marc A. Saltzman, Michael J. Castine, Gregory L. Ortega, Young M. Choi, Craig H. Reynolds, Frankie Ann Brescia, Rita Kramer, Aimee D. Kohn, John P. Micha, Jessica M. Rhee, Satish Shah, David A. Riseberg, William Kevin Patterson, Jean-Paul Salmon, Chantal Andre, Alain Bols, Randal D'hondt, Sylvie Luce, Claire Nouwynck, Gino Pelgrims, Vincent Richard, Johan Verschuere, Kurt Geldhof, Clemens Caspar, Rongcheng Luo, Otakar Bednarik, Kathrin Schwedler, Marcus Schmidt, Romy Neumeister, Joachim Bischoff, Brigitte Rack, Roland Repp, Stefan Fries, Ralf Adrion, Volker Schulz, Peter Klare, Mahmoud Danei, Dirk Ossenbuhl, Jakob Manfred Kusche, Frank Griesinger, Jose Manuel Baena Canada, Purificacion Martinez del Prado, David Machover, Didier Mayeur, Nathalie Trufflandier, Valerie Delecroix, Mireille Mousseau, Marie-Ange Mouret-Reynier, Jean-Marc Nabholtz, Anula D. Chetiyawardana, Christos Papandreou, Lajos Hornyak, Zsolt Faluhelyi, Erzsebet Simo, Mario Di Palma, Francesco Cognetti, Gabriella Gorzegno, Luigi Dogliotti, Cesare Gridelli, Alfredo Falcone, Hector Soto Parra, Calogero Buscarino, Seock-Ah Im, Benito Sanchez Llamas, Wouter Dercksen, Franciscus Erdkamp, Jan B. Ruit, Hans Braun, Joanneke E.A. Portielje, Aydin Ciltas, Suleyman Buyukberber, Mustafa Benekli, Andrew J. Zahalsky, Rebecca Jaslow, Gary W. Thomas, Archana Maini, Israel Wiznitzer, Ali Khojasteh, Manuel Francisco Gonzalez, Lynn R. Kong, Aruna Padmanabhan, William A. Conkright, Sandra M. Swain, Douglas E. Faig, Kirti Jain, Ronald H. Yanagihara, Yvonne Ottaviano, Andrew Delmas, Heather A. Steele, Gordon K. Rainey, Penelope J. Harris, Jason K. Burris, Erik J. Rupard, Esther Tan, Pat W. Whitworth, Abby R. Bova, Ian C. Anderson, Mihran Shirinian, Caesar Tin-u, Timothy J. O'Rourke, Michael S. Roberts, Michael Francisco, A. Scott Pierson, Peter D. Byeff, Peter A. Kovach, John R. Caton, Mark Urban Rarick, William G. Schimidt, Alison T. Stopeck, Rachel Swart, Maria Regina Carrillo Flores, Carlos A. Alemany, Brennely Lozada, Paul L. Weinstein, Wei Wang, Michael Porubcin, David M. Ellison, George F. Geils, Edgardo Rivera, Mahmoud Charif, Martin, M, Holmes, F, Ejlertsen, B, Delaloge, S, Moy, B, Iwata, H, von Minckwitz, G, Chia, S, Mansi, J, Barrios, C, Gnant, M, Tomasevic, Z, Denduluri, N, Separovic, R, Gokmen, E, Bashford, A, Borrego, M, Kim, S, Jakobsen, E, Ciceniene, A, Inoue, K, Overkamp, F, Heijns, J, Armstrong, A, Link, J, Abraham, A, Bryce, J, Wong, A, Moran, S, Yao, B, Xu, F, Auerbach, A, Buyse, M, Chan, A, and Bidoli, P

Subjects
0301 basic medicine, Time Factors, Receptor, ErbB-2, Clinical Trial, Phase III, Receptor, ErbB-2/metabolism, Administration, Oral, Kaplan-Meier Estimate, exteNET, 0302 clinical medicine, Japan, Trastuzumab, Antineoplastic Combined Chemotherapy Protocols, pan-HER tyrosine kinase inhibitor, Mastectomy, Antineoplastic Combined Chemotherapy Protocols/administration & dosage, Middle Aged, neratinib, trastuzumab, breast cancer, adjuvant, Multicenter Study, Treatment Outcome, Oncology, Antibodies, Monoclonal, Humanized/adverse effects, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Randomized Controlled Trial, Neratinib, Quinolines, Neoplasm Invasiveness/pathology, Female, medicine.drug, Adult, medicine.medical_specialty, Quinolines/administration & dosage, Breast Neoplasms, Placebo, Antibodies, Monoclonal, Humanized, Risk Assessment, Disease-Free Survival, Drug Administration Schedule, Trastuzumab/administration & dosage, 03 medical and health sciences, Breast cancer, Breast Neoplasms/drug therapy, Double-Blind Method, Internal medicine, Journal Article, medicine, Adjuvant therapy, Humans, Comparative Study, Neoplasm Invasiveness, HER2-positive breast cancer, Neoplasm Staging, Proportional Hazards Models, Intention-to-treat analysis, Dose-Response Relationship, Drug, business.industry, medicine.disease, Survival Analysis, Mastectomy/methods, Surgery, Clinical trial, Regimen, 030104 developmental biology, business, Follow-Up Studies
Abstract

BACKGROUND: ExteNET showed that 1 year of neratinib, an irreversible pan-HER tyrosine kinase inhibitor, significantly improves 2-year invasive disease-free survival after trastuzumab-based adjuvant therapy in women with HER2-positive breast cancer. We report updated efficacy outcomes from a protocol-defined 5-year follow-up sensitivity analysis and long-term toxicity findings. METHODS: In this ongoing randomised, double-blind, placebo-controlled, phase 3 trial, eligible women aged 18 years or older (≥20 years in Japan) with stage 1-3c (modified to stage 2-3c in February, 2010) operable breast cancer, who had completed neoadjuvant and adjuvant chemotherapy plus trastuzumab with no evidence of disease recurrence or metastatic disease at study entry. Patients who were eligible patients were randomly assigned (1:1) via permuted blocks stratified according to hormone receptor status (hormone receptor-positive vs hormone receptor-negative), nodal status (0 vs 1-3 vs or ≥4 positive nodes), and trastuzumab adjuvant regimen (given sequentially vs concurrently with chemotherapy), then implemented centrally via an interactive voice and web-response system, to receive 1 year of oral neratinib 240 mg/day or matching placebo. Treatment was given continuously for 1 year, unless disease recurrence or new breast cancer, intolerable adverse events, or consent withdrawal occurred. Patients, investigators, and trial funder were masked to treatment allocation. The predefined endpoint of the 5-year analysis was invasive disease-free survival, analysed by intention to treat. ExteNET is registered with ClinicalTrials.gov, number NCT00878709, and is closed to new participants. FINDINGS: Between July 9, 2009, and Oct 24, 2011, 2840 eligible women with early HER2-positive breast cancer were recruited from community-based and academic institutions in 40 countries and randomly assigned to receive neratinib (n=1420) or placebo (n=1420). After a median follow-up of 5·2 years (IQR 2·1-5·3), patients in the neratinib group had significantly fewer invasive disease-free survival events than those in the placebo group (116 vs 163 events; stratified hazard ratio 0·73, 95% CI 0·57-0·92, p=0·0083). The 5-year invasive disease-free survival was 90·2% (95% CI 88·3-91·8) in the neratinib group and 87·7% (85·7-89·4) in the placebo group. Without diarrhoea prophylaxis, the most common grade 3-4 adverse events in the neratinib group, compared with the placebo group, were diarrhoea (561 [40%] grade 3 and one [BACKGROUND: ExteNET showed that 1 year of neratinib, an irreversible pan-HER tyrosine kinase inhibitor, significantly improves 2-year invasive disease-free survival after trastuzumab-based adjuvant therapy in women with HER2-positive breast cancer. We report updated efficacy outcomes from a protocol-defined 5-year follow-up sensitivity analysis and long-term toxicity findings.METHODS: In this ongoing randomised, double-blind, placebo-controlled, phase 3 trial, eligible women aged 18 years or older (≥20 years in Japan) with stage 1-3c (modified to stage 2-3c in February, 2010) operable breast cancer, who had completed neoadjuvant and adjuvant chemotherapy plus trastuzumab with no evidence of disease recurrence or metastatic disease at study entry. Patients who were eligible patients were randomly assigned (1:1) via permuted blocks stratified according to hormone receptor status (hormone receptor-positive vs hormone receptor-negative), nodal status (0 vs 1-3 vs or ≥4 positive nodes), and trastuzumab adjuvant regimen (given sequentially vs concurrently with chemotherapy), then implemented centrally via an interactive voice and web-response system, to receive 1 year of oral neratinib 240 mg/day or matching placebo. Treatment was given continuously for 1 year, unless disease recurrence or new breast cancer, intolerable adverse events, or consent withdrawal occurred. Patients, investigators, and trial funder were masked to treatment allocation. The predefined endpoint of the 5-year analysis was invasive disease-free survival, analysed by intention to treat. ExteNET is registered with ClinicalTrials.gov, number NCT00878709, and is closed to new participants.FINDINGS: Between July 9, 2009, and Oct 24, 2011, 2840 eligible women with early HER2-positive breast cancer were recruited from community-based and academic institutions in 40 countries and randomly assigned to receive neratinib (n=1420) or placebo (n=1420). After a median follow-up of 5·2 years (IQR 2·1-5·3), patients in the neratinib group had significantly fewer invasive disease-free survival events than those in the placebo group (116 vs 163 events; stratified hazard ratio 0·73, 95% CI 0·57-0·92, p=0·0083). The 5-year invasive disease-free survival was 90·2% (95% CI 88·3-91·8) in the neratinib group and 87·7% (85·7-89·4) in the placebo group. Without diarrhoea prophylaxis, the most common grade 3-4 adverse events in the neratinib group, compared with the placebo group, were diarrhoea (561 [40%] grade 3 and one [INTERPRETATION: At the 5-year follow-up, 1 year of extended adjuvant therapy with neratinib, administered after chemotherapy and trastuzumab, significantly reduced the proportion of clinically relevant breast cancer relapses-ie, those that might lead to death, such as distant and locoregional relapses outside the preserved breast-without increasing the risk of long-term toxicity. An analysis of overall survival is planned after 248 events.FUNDING: Wyeth, Pfizer, and Puma Biotechnology.

Published
2017

24. Globalization of clinical research in oncology: Status, challenges, and future directions.

Author

Tečić Vuger A, Separovic R, Tolaney SM, and Trapani D

Abstract

Purpose: Cancer is the second-leading cause of death worldwide, and its burden is increasing around the world, particularly in low- and middle-income countries (LMICs). Yet, cancer research has historically been conducted primarily in high-income countries (HICs)., Methods: In this review, we describe the results of our literature search into the current state of international cancer trials, including the benefits, challenges, limitations, and ethical concerns regarding the international conduct of HIC-led trials. We also propose some possible means of addressing these challenges and overcoming these barriers to extend the benefits of cancer research to people around the world., Results: Over the last several decades, there has been a shift toward inclusion of investigators and participants from LMICs in pivotal cancer clinical trials., Conclusions: While inclusion of LMIC countries has benefits, including increased diversity of participant populations, investment in research infrastructure in LMICs, and potential expansion of cancer treatment options around the world, the continued leadership of most trials by HICs presents ethical concerns, including potential exploitation of researchers and participants from LMICs, lack of focus on cancer types prevalent in all participating regions, and disparities in access to approved therapies once the trial is complete., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Sara M. Tolaney reports consulting or advisory roles for Novartis, Pfizer (SeaGen), Merck, Eli Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squibb, CytomX Therapeutics, Daiichi Sankyo, Gilead, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, Sumitovant Biopharma, Umoja Biopharma, Artios Pharma, Menarini/Stemline, Aadi Bio, Bayer, Incyte Corp, Jazz Pharmaceuticals, Natera, Tango Therapeutics, Systimmune, eFFECTOR, Hengrui USA, Cullinan Oncology, Circle Pharma, Arvinas, BioNTech, and Johnson&Johnson; research funding from Genentech/Roche, Merck, Exelixis, Pfizer, Lilly, Novartis, Bristol Myers Squibb, Eisai, AstraZeneca, Gilead, NanoString Technologies, Seattle Genetics, OncoPep, and Jazz Pharmaceuticals; and travel support from Eli Lilly, Sanofi, Gilead, Jazz Pharmaceuticals, and Pfizer. The remaining authors declare no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Published
2024
Full Text
View/download PDF

25. Immunohistochemical analysis of ER, PR, HER-2, CK 5/6, p63 and EGFR antigen expression in medullary breast cancer.

Author

Matkovic B, Juretic A, Separovic V, Novosel I, Separovic R, Gamulin M, and Kruslin B

Subjects
Adult, Aged, Aged, 80 and over, Axilla surgery, Breast Neoplasms pathology, Breast Neoplasms surgery, Carcinoma, Medullary secondary, Carcinoma, Medullary surgery, ErbB Receptors metabolism, Estrogen Receptor alpha metabolism, Female, Humans, Immunoenzyme Techniques, Keratin-5 metabolism, Keratin-6 metabolism, Lymphatic Metastasis, Mastectomy, Membrane Proteins metabolism, Middle Aged, Prognosis, Receptor, ErbB-2 metabolism, Receptors, Progesterone metabolism, Retrospective Studies, Survival Rate, Biomarkers, Tumor metabolism, Breast Neoplasms metabolism, Carcinoma, Medullary metabolism
Abstract

Aims and Background: Recent publications of breast cancer classification based on gene expression profile analyses indicate that medullary breast carcinomas (MBC) may be considered part of the basal-like carcinoma spectrum made up of ER-negative, PR-negative and HER-2-negative cells ("triple-negative phenotype"). On the other hand, there are also data showing that a proportion of MBC and atypical MBC (AMBC) is ER, PR and/or HER-2 positive. Therefore, we have decided to immunohistochemically analyze ER, PR, HER-2 and basal/myoepithelial markers CK 5/6, p63 and EGFR expression in our archival paraffin-embedded MBC and AMBC samples from 48 patients., Methods: Immunohistochemical evaluation of samples which were derived from patients operated on at our two hospitals between 1999 and 2005., Results: Typical MBC was found in 39 patients and AMBC in 9 patients. The patients ranged in age from 32 to 84 years (median 55). Modified radical mastectomy with axillary dissection was performed in 30/48 patients (63%) while breast segmentectomy with axillary dissection was performed in 18/48 patients (37%). Metastases in axillary lymph nodes were observed in 15/48 patients (31%). ER positivity was present in 3/48 patients (6%), PR positivity in 8/48 (17%), and a positive HER-2 reaction was present in 14/48 patients (29%). CK 5/6 was positive in 20/48, p63 in 24/48 and EGFR in 8/48 patients. Adjuvant therapy was applied in all but 2 patients. Alive were 45/48 (94%) of patients. With the exception of PR expression, 39 patients with typical MBC and 9 patients with AMBC were comparable in the analyzed parameters. Positive HER-2 antigen expression in the analyzed sample was not found to be associated to a statistically significant degree with the MBC or AMBC histological tumor type, tumor size, axillary lymph node metastases, ER and PR status nor with patient survival., Conclusions: The data from our study seem to be generally comparable with the relatively scarce published data on clinicopathological parameters of MBC and AMBC.

Published
2008
Full Text
View/download PDF

26. Expression of cancer/testis tumor associated antigens in cervical squamous cell carcinoma.

Author

Sarcevic B, Spagnoli GC, Terracciano L, Schultz-Thater E, Heberer M, Gamulin M, Krajina Z, Oresic T, Separovic R, and Juretic A

Subjects
Antibodies, Monoclonal, Antigens, Neoplasm immunology, Carcinoma, Squamous Cell pathology, Female, Gene Expression Regulation, Neoplastic, Humans, Immunoblotting, Immunohistochemistry, Male, Melanoma-Specific Antigens, Neoplasm Invasiveness, Neoplasm Proteins analysis, Tumor Cells, Cultured, Uterine Cervical Neoplasms pathology, Antigens, Neoplasm analysis, Carcinoma, Squamous Cell immunology, Testicular Neoplasms immunology, Uterine Cervical Neoplasms immunology
Abstract

We investigated the expression of tumor-associated antigens (TAA) of the cancer/testis (C/T) gene family in cervical squamous cell carcinomas. First, we focused on the HeLa cervical cancer derived cell line, and we found that it expresses MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A6, MAGE-A12, GAGE-3/6, LAGE-1, and PRAME genes, encoding defined C/T TAA. In contrast, no expression of MAGE-A10, BAGE, GAGE-1/2, or NY-ESO-1 genes was observed. Corresponding gene products could also be detected by immunoblotting and immunocytochemistry, taking advantage of monoclonal antibodies recognizing discrete TAA. Capitalizing on these data, a monoclonal antibody predominantly recognizing MAGE-A4 TAA in paraffin-embedded sections (57B) was used to investigate the C/T gene expression in clinical tumor samples. A group of 60 patients was studied, and 57B positivity was detectable to different extents in 33% of the cases (20/60). In 13 of them (21%), staining of over 50% of the tumor cells was evident, whereas healthy cells always scored negative. Remarkably, MAGE-A4 expression was significantly (p < 0.05) more frequently detectable in poorly differentiated tumors (8/13) than in well-differentiated or moderately differentiated cancers (3/15 and 9/32, respectively) and in stage FIGO II as compared with stage FIGO Ib tumors (12/23 and 5/24, respectively, p = 0.04). Interestingly, staining was mostly nuclear in well-differentiated tumors, but involved both nuclei and cytoplasm in less differentiated cancers. Positivities of comparable frequency were also detectable in a smaller series of specimens upon staining with MAGE-A1- or NY-ESO-1/LAGE-1-specific reagents. Considering the high tumor specificity of C/T TAA, our data provide the rationale for the design of immunotherapy procedures targeting these antigens in cervical cancers., (Copyright 2003 S. Karger AG, Basel)

Published
2003
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results