MAX SENNA MANO
Projetos de Pesquisa
Unidades Organizacionais
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
8 resultados
Resultados de Busca
Agora exibindo 1 - 8 de 8
- Reply to: Mastectomy skin flap thickness(2018) MARTA, Gustavo Nader; POORTMANS, Philip; BARROS, Alfredo C. de; FILASSI, Jose Roberto; FREITAS-JUNIOR, Ruffo; AUDISIO, Riccardo A.; MANO, Max Senna; METERISSIAN, Sarkis; DESNYDER, Sarah M.; BUCHHOLZ, Thomas A.; HIJAL, Tarek
- Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer(2019) MINCKWITZ, G. von; HUANG, C. -S.; MANO, M. S.; LOIBL, S.; MAMOUNAS, E. P.; UNTCH, M.; WOLMARK, N.; RASTOGI, P.; SCHNEEWEISS, A.; REDONDO, A.; FISCHER, H. H.; JACOT, W.; CONLIN, A. K.; ARCE-SALINAS, C.; WAPNIR, I. L.; JACKISCH, C.; DIGIOVANNA, M. P.; FASCHING, P. A.; CROWN, J. P.; WUELFING, P.; SHAO, Z.; CAREMOLI, E. Rota; WU, H.; LAM, L. H.; TESAROWSKI, D.; SMITT, M.; DOUTHWAITE, H.; SINGEL, S. M.; GEYER JR., C. E.BACKGROUND Patients who have residual invasive breast cancer after receiving neoadjuvant chemotherapy plus human epidermal growth factor receptor 2 (HER2)-targeted therapy have a worse prognosis than those who have no residual cancer. Trastuzumab emtansine (T-DM1), an antibody-drug conjugate of trastuzumab and the cytotoxic agent emtansine (DM1), a maytansine derivative and microtubule inhibitor, provides benefit in patients with metastatic breast cancer that was previously treated with chemotherapy plus HER2-targeted therapy. METHODS We conducted a phase 3, open-label trial involving patients with HER2-positive early breast cancer who were found to have residual invasive disease in the breast or axilla at surgery after receiving neoadjuvant therapy containing a taxane (with or without anthracycline) and trastuzumab. Patients were randomly assigned to receive adjuvant T-DM1 or trastuzumab for 14 cycles. The primary end point was invasive disease-free survival (defined as freedom from ipsilateral invasive breast tumor recurrence, ipsilateral locoregional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause). RESULTS At the interim analysis, among 1486 randomly assigned patients (743 in the T-DM1 group and 743 in the trastuzumab group), invasive disease or death had occurred in 91 patients in the T-DM1 group (12.2%) and 165 patients in the trastuzumab group (22.2%). The estimated percentage of patients who were free of invasive disease at 3 years was 88.3% in the T-DM1 group and 77.0% in the trastuzumab group. Invasive disease-free survival was significantly higher in the T-DM1 group than in the trastuzumab group (hazard ratio for invasive disease or death, 0.50; 95% confidence interval, 0.39 to 0.64; P<0.001). Distant recurrence as the first invasive-disease event occurred in 10.5% of patients in the T-DM1 group and 15.9% of those in the trastuzumab group. The safety data were consistent with the known safety profile of T-DM1, with more adverse events associated with T-DM1 than with trastuzumab alone. CONCLUSIONS Among patients with HER2-positive early breast cancer who had residual invasive disease after completion of neoadjuvant therapy, the risk of recurrence of invasive breast cancer or death was 50% lower with adjuvant T-DM1 than with trastuzumab alone.
- HER2-targeted therapy in breast cancer: A systematic review of neoadjuvant trials(2013) DENT, Susan; OYAN, Basak; HONIG, Amd; MANO, Max; HOWELL, SachaTargeting human epidermal growth factor receptor 2 (HER2) during or in sequence with chemotherapy improves overall survival in metastatic and early HER2-overexpressing breast cancer. In this paper we systematically review neoadjuvant clinical trial data in HER2-positive breast cancer and discuss key unanswered clinical questions. All trials of HER2-targeted neoadjuvant therapy were identified through non-date-limited searches of PubMED (R) and Biosis (R) and congress abstract book searches from 2000-2011. Eligible trials were prospective, had at least 10 patients and a clear definition of pathological complete response (pCR) rate. A total of 50 trials fulfilled the eligibility criteria; 41 single-arm phase II studies were identified, 37 with trastuzumab and 4 with lapatinib, with significant variability in baseline tumour characteristics and pCR rates (range 12-66.7%). Of 9 randomised phase II/III trials, 4 assessed the addition of trastuzumab to chemotherapy and a further 5 randomised trials assessed different HER2-targeting approaches. Four of these studies assessed dual HER2-targeting approaches, which universally increased pCR at the expense of increased non-cardiac toxicity when lapatinib, but not pertuzumab, was added to trastuzumab. Significant advances have been made in HER2 targeting, resulting in a marked increase in the number of breast cancer patients experiencing tumour pCR. Mature data from randomised neoadjuvant and adjuvant studies are awaited for survival outcomes with combination targeted approaches. Unanswered questions centre on the individualisation of therapy and include; which, if any, chemotherapy backbone should be used, and which patients need dual HER2 blockade? (C) 2013 Elsevier Ltd. All rights reserved.
- Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent or metastatic breast cancer (PERUSE)(2019) BACHELOT, T.; CIRUELOS, E.; SCHNEEWEISS, A.; PUGLISI, F.; PERETZ-YABLONSKI, T.; BONDARENKO, I.; PALUCH-SHIMON, S.; WARDLEY, A.; MEROT, J. -L.; TOIT, Y. du; EASTON, V.; LINDEGGER, N.; MILES, D.; BOUZID, Kamel; CAMPONE, Mario; COUDERT, Bruno; NOWECKI, Zbigniew; ERRIHANI, Hassan; DALENC, Florence; FERREIRA, Ana; MANO, Max; RICCI, Francesco; KALOFONOS, Haralabos; ANDREETTA, Claudia; MONTEMURRO, Filippo; BARRETT, Sophie; ZHANG, Qingyuan; MAVROUDIS, Dimitris; MATUS, Juan; BEATO, Carlos; HU, Xichun; GAAFAR, Rabab; AZEEM, Hamdy Abdel; PERRIN, Christophe; ETTL, Johannes; LANG, Istvan; VERMA, Sunil; LI, Huiping; BRAIN, Etienne; HOFFMANN, Oliver; CARIELLO, Anna; TONDINI, Carlo; ALTWEGEIRI, Taher; LOMAN, Niklas; LUX, Michael; FRASSOLDATI, Antonio; AZIZ, Zeba; SALAS, Fernando; STREB, Joanna; WRONSKI, Andrzej; BELTRAN, Salomon Menjon; CICIN, Irfan; SCHMID, Peter; LAING, Robert; TONG, Zhongsheng; BOER, Katalin; JUHASZ, Balazs; GIANNI, Luca; CURIGLIANO, Giuseppe; JUAREZ, Alejandro; MATOS, Erika; USLU, Ruchan; WILDIERS, Hans; CRUZ, Marcelo; BOURGEOIS, Hugues; SCHUMANN, Raquel von; STEMMER, Salomon; VASQUEZ, Flavia Morales; DOMINGUEZ, Adriana; WOJTUKIEWICZ, Marek; TRIFUNOVIC, Jasna; ILLARRAMENDI, Jose Juan; GARCIA, Laura; PERON, Yann Izarzugaza; ECHARRI, Maria Jose; VOITKO, Natliia; WHEATLEY, Duncan; WATERS, Simon; BOER, Richard De; JERUSALEM, Guy; COCQUYT, Veronique; BARRIOS, Carlos; PANASCI, Lawrence; MATTSON, Johanna; TANNER, Minna; GOZY, Michel; VASILOPOULOS, Georgios; REVESZ, Janos; LATINI, Luciano; GRIDELLI, Cesare; LAZARO, Jesus; GONZALEZ, Antonio; MOLINS, Agusti Barnadas; MARTINEZ, Eduardo; ALARCON, Jesus; ARANCE, Ana; KLINT, Leif; KOVALYOV, Oleksiy; BAIRD, Richard; YEO, Belinda; MCCARTHY, Nicole; GREIL, Richard; WANG, Shusen; ARTIGNAN, Xavier; AUGEREAU, Paule; JUHASZ-BOESS, Ingolf; NGAN, Roger; GOLDBERG, Hadassah; COSTANZO, Francesco Di; FERRAU, Francesco; ALEKNAVICIUS, Eduardas; RASHID, Kamran; COSTA, Luis; GARCIA, Jose Angel; CRUZ, Luis Ruiz de la; LOPEZ, Rafael Lopez; VAL, Olga Del; OZYILKAN, Ozgur; AZRIBI, Fathi; VERRILL, Mark; TURNER, Nicholas; BEITH, Jane; PETZER, Andreas; ANDRADE, Jurandyr; BERNSTEIN, Vanessa; RAYSON, Daniel; ELDIN, Ibtessam Saad; ACHILLE, Mihaela; MUELLER, Volkmar; GENNARI, Alessandra; CASCINU, Stefano; GHOSN, Marwan; EL-SAGHIR, Nagi; BOSCH, Joan Van den; OOSTERKAMP, Rianne; KUKULSKA, Monika; PELAEZ, Ignacio; HERNANDEZ, Carolina; GORDON, Maria del Mar; DALMAU, Elsa; ALONSO, Jose Luis; AKSOY, Sercan; COSKUN, Hasan Senol; SHPARYK, Yaroslav; VARUGHESE, Mohini; PANWAR, Udaiveer; BARRACLOUGH, Lisa; LEVITT, Nicola; HICKS, Jonathan; RIGG, Anna; ALLEN, Mark; CASTILLO, Cecila; FEIN, Luis Enrique; STUART-HARRIS, Robin; SINGER, Christian; STOEGER, Herbert; SMILJANIC, Sasha; FENG, Jifeng; CEDENO, Miguel; BERDAH, Jean Francois; ORFEUVRE, Hubert; GONCALVES, Anthony; GRISCHKE, Eva-Maria; SIMON, Eike; WAGNER, Steffen; EFREMIDOU, Anna; PAPAZISIS, Konstantinos; EVRON, Ella; INBAR, Moshe; BARUCH, Noa Ben; GEFFEN, David; KARMINSKY, Natalya; RUGGERI, Enzo Maria; LUIGI, Cavanna; GRASSO, Donatella; JUOZAITYTE, Elona; CID, Jeronimo Rafael Rodriguez; ROERDINK, Henk; SIDDIQI, Neelum; COELHO, Jose Luis Passos; GARRE, Elisa Garcia; GARCIA, Andres; JANEZ, Noelia Martinez; CEBALLOS, Maria Helena Lopez; MELE, Mireia; GARCIA, Maria; ARCEDIANO, Alberto; MCADAM, Karen; PERREN, Timothy; HICKS, Jonathan; TAYLOR, Wendy; HUMPHREYS, Alison; VERA, Raul; STEGER, Guenther; ANDEL, Johannes; GREVE, Jacques de; HUIZING, Manon; HEGG, Roberto; JOY, Anil; SEHDEV, Sandeep; KUTNER, Riina; RUOHOLA, Johanna; DOHOLLOU, Nadine; GROSJEAN, Jessica; LAPLAIGE, Philippe; LARGILLIER, Remy; MARTIN, Philippe; POTTIER, Virginie; ALEXANDRE, Jerome; CHRISTENSEN, Bernd; ZAHM, Dirk-Michael; KHANDAN, Fariba; LUECK, Hans-Joachim; FOUNTZILAS, Georgios; FRIED, Georgeta; GIACOBINO, Alice; BONETTI, Andrea; GUERRA, Yanin Chavarri; WARMERDAM, Laurens Van; VELDEN, Annette Van der; VRIJALDENHOVEN, Suzan; JONGH, Felix de; CAVERO, Milagros; CONEJERO, Raquel Andres; MURIAS, Adolfo; SAURA, Salvador; OLTRA, Amparo; REDONDO, Andres; RIBELLES, Nuria; BACHMEIER, Kilian; JOFFE, Johnathan; CHAKRABORTI, Prabir; BERESFORD, Mark; BUTT, Mohammad; POOLE, Christopher; YORDI, Gassan; WOODWARD, Natasha; AMORIM, Gilberto; CALIFARETTI, Nadia; FOX, Susan; ROBIDOUX, Andre; LI, NanLi; LI, Nenxiao; JIANG, Jun; SORIA, Tannia; PADRIK, Peeter; SAARNI, Outi; GENET, Dominique; CATALA, Stephanie; BARLETTA, Hugues; TEIXEIRA, Luis; FACCHINI, Thomas; HESSE, Tobias; KUEHN, Thorsten; OBER, Angelika; REPP, Roland; SCHROEDER, Willibald; PECTASIDES, Dimitrios; BODOKY, Gyorgy; KAHAN, Zsuzsanna; JIVELIOUK, Irina; ROSENGARTEN, Ora; ALABISO, Oscar; PEREZ, Mario; WOUW, Yes Van de; SMOK-KALWAT, Jolanta; DAMASCENO, Margarida; SOUSA, Gabriela; ABULKHAIR, Omalkhair; TORRES, Antonio Anton; MARTINEZ, Maria Purificacion; MATA, Jesus Garcia; JERICO, Marta Santisteban Jesus Florian; LLOMBART, Antonio; SANCHEZ, Rosa; TORREGO, Juan Carlos; GARATE, Clara Olier; RODRIGUEZ, Cesar; LLORENTE, Rosa; PRADO, Diego Soto de; CORTES, Javier; LLORCA, Cristina; GALAN, Antonio; VILLARO, Gemma Vinas; NARBE, Ulrik; BJOMEKLETT, Helena Granstam; WESTWELL, Sarah; NEWBY, Jackie; JAFRI, Mariam; RODRIGUEZ, Robinson; ALONSO, IsabelBackground: Pertuzumab combined with trastuzumab and docetaxel is the standard first-line therapy for HER2-positive metastatic breast cancer, based on results from the phase III CLEOPATRA trial. PERUSE was designed to assess the safety and efficacy of investigator-selected taxane with pertuzumab and trastuzumab in this setting. Patients and methods: In the ongoing multicentre single-arm phase IIIb PERUSE study, patients with inoperable HER2-positive advanced breast cancer (locally recurrent/metastatic) (LR/MBC) and no prior systemic therapy for LR/MBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab [8 mg/kg loading dose, then 6 mg/kg every 3 weeks (q3w)] and pertuzumab (840 mg loading dose, then 420 mg q3w) until disease progression or unacceptable toxicity. The primary end point was safety. Secondary end points included overall response rate (ORR) and progression-free survival (PFS). Results: Overall, 1436 patients received at least one treatment dose (initially docetaxel in 775 patients, paclitaxel in 589, nab-paclitaxel in 65; 7 discontinued before starting taxane). Median age was 54 years; 29% had received prior trastuzumab. Median treatment duration was 16 months for pertuzumab and trastuzumab and 4 months for taxane. Compared with docetaxel-containing therapy, paclitaxel-containing therapy was associated with more neuropathy (all-grade peripheral neuropathy 31% versus 16%) but less febrile neutropenia (1% versus 11%) and mucositis (14% versus 25%). At this preliminary analysis (52 months' median follow-up), median PFS was 20.6 [95% confidence interval (CI) 18.9-22.7] months overall (19.6, 23.0 and 18.1 months with docetaxel, paclitaxel and nab-paclitaxel, respectively). ORR was 80% (95% CI 78%-82%) overall (docetaxel 79%, paclitaxel 83%, nab-paclitaxel 77%). Conclusions: Preliminary findings from PERUSE suggest that the safety and efficacy of first-line pertuzumab, trastuzumab and taxane for HER2-positive LR/MBC are consistent with results from CLEOPATRA. Paclitaxel appears to be a valid alternative taxane backbone to docetaxel, offering similar PFS and ORR with a predictable safety profile.
- The ENCHANT-1 trial (NCT01677455): An open label multicenter phase 2 proof of concept study evaluating first line ganetespib monotherapy in women with metastatic HER2 positive or triple negative obreast cancer (TNBC)(2013) AWADA, A.; SPECTOR, N.; EL-HARIRY, I.; RODRIGUEZ, A. A.; ERBAN, J. K.; CORTES, J.; GOMEZ, H.; KONG, A.; HICKISH, T.; FEIN, L.; VAHDAT, L.; MACPHERSON, I.; CANON, J-L; MANSOOR, S.; GIOVANNE, A.; MCADAM, K.; VUKOVIC, V. M.; YALCIN, I.; BRADLEY, R.; PROIA, D.; MANO, M. S.; PEREZ, E. A.; CAMERON, D. A.
conferenceObject KATHERINE: Trastuzumab emtansine vs trastuzumab as adjuvant therapy in patients with HER2-positive early breast cancer(2019) MAMOUNAS, Eleftherios P.; GEYER JR., Charles E.; HUANG, Chiun-Sheng; MANO, Max S.; LOIBL, Sibylle; UNTCH, Michael; WOLMARK, Norman; RASTOGI, Priya; SCHNEEWEISS, Andreas; REDONDO, Andres; FISCHER, Hans H.; JACOT, William; CONLIN, Alison K.; ARCE-SALINAS, Claudia; WAPNIR, Irene L.; JACKISCH, Christian; DIGIOVANNA, Michael P.; FASCHING, Peter A.; CROWN, John P.; WUELFING, Pia; SHAO, Zhimin; CAREMOLI, Elena Rota; WU, Haiyan; LAM, Lisa H.; TESAROWSKI, David; SMITT, Melanie; DOUTHWAITE, Hannah; SINGEL, Stina M.; MINCKWITZ, Gunter von- Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial(2011) GIANNI, Luca; DAFNI, Urania; GELBER, Richard D.; AZAMBUJA, Evandro; MUEHLBAUER, Susanne; GOLDHIRSCH, Aron; UNTCH, Michael; SMITH, Ian; BASELGA, Jose; JACKISCH, Christian; CAMERON, David; MANO, Max; PEDRINI, Jose Luiz; VERONESI, Andrea; MENDIOLA, Cesar; PLUZANSKA, Anna; SEMIGLAZOV, Vladimir; VRDOLJAK, Eduard; ECKART, Michael J.; SHEN, Zhenzhou; SKIADOPOULOS, George; PROCTER, Marion; PRITCHARD, Kathleen I.; PICCART-GEBHART, Martine J.; BELL, RichardBackground Treatment with adjuvant trastuzumab for 1 year improves disease-free survival and overall survival in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. We aimed to assess disease-free survival and overall survival after a median follow-up of 4 years for patients enrolled on the Herceptin Adjuvant (HERA) trial. Methods The HERA trial is an international, multicentre, randomised, open-label, phase 3 trial comparing treatment with trastuzumab for 1 and 2 years with observation after standard neoadjuvant, adjuvant chemotherapy, or both in patients with HER2-positive early breast cancer. The primary endpoint was disease-free survival. After a positive first interim analysis at a median follow-up of 1 year for the comparison of treatment with trastuzumab for 1 year with observation, event-free patients in the observation group were allowed to cross over to receive trastuzumab. We report trial outcomes for the 1-year trastuzumab and observation groups at a median follow-up of 48.4 months (IQR 42.0-56.5) and assess the effect of the extensive crossover to trastuzumab. Our analysis was by intention-to-treat. The HERA trial is registered with the European Clinical Trials Database, number 2005-002385-11. Findings The HERA trial population comprised 1698 patients randomly assigned to the observation group and 1703 to the 1-year trastuzumab group. Intention-to-treat analysis of disease-free survival showed a significant benefit in favour of patients in the 1-year trastuzumab group (4-year disease-free survival 78.6%) compared with the observation group (4-year disease-free survival 72.2%; hazard ratio [HR] 0.76; 95% CI 0.66-0.87; p<0.0001). Intention-to-treat analysis of overall survival showed no significant difference in the risk of death (4-year overall survival 89.3% vs 87.7%, respectively; HR 0.85; 95% CI 0.70-1.04; p=0.11). Overall, 885 patients (52%) of the 1698 patients in the observation group crossed over to receive trastuzumab, and began treatment at median 22.8 months (range 4.5-52.7) from randomisation. In a non-randomised comparison, patients in the selective-crossover cohort had fewer disease-free survival events than patients remaining in the observation group (adjusted HR 0.68; 95% CI 0.51-0.90; p=0.0077). Higher incidences of grade 3-4 and fatal adverse events were noted on 1-year trastuzumab than in the observation group. The most common grade 3 or 4 adverse events, each in less than 1% of patients, were congestive cardiac failure, hypertension, arthralgia, back pain, central-line infection, hot flush, headache, and diarrhoea. Interpretation Treatment with adjuvant trastuzumab for 1 year after chemotherapy is associated with significant clinical benefit at 4-year median follow-up. The substantial selective crossover of patients in the observation group to trastuzumab was associated with improved outcomes for this cohort.
- Multidisciplinary international survey of post-operative radiation therapy practices after nipple-sparing or skin-sparing mastectomy(2017) MARTA, Gustavo Nader; POORTMANS, Philip; BARROS, Alfredo C. de; FILASSI, Jose Roberto; FREITAS JUNIOR, Ruffo; AUDISIO, Riccardo A.; MANO, Max Senna; METERISSIAN, Sarkis; DESNYDER, Sarah M.; BUCHHOLZ, Thomas A.; HIJAL, TarekPurpose/Objective(s): Skin sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) have entered routine surgical practice for breast cancer, though their oncologic safety has not been established in randomized controlled trials. The aim of this study was to evaluate and compare radiation oncologists' and breast surgeons' opinions concerning the indications of post-operative radiation therapy (PORT) after SSM and NSM. Materials/Methods: Radiation oncologists and breast surgeons from North America, South America and Europe were invited to contribute in this study. A 22-question survey was used to evaluate their opinions. Results: A total of 550 physicians (298 radiation oncologists and 252 breast surgeons) answered the survey. The majority of responders affirmed that PORT should be performed in early-stage (stages I and II) breast cancer for patients who present with risk factors for relapse after SSM and NSM. They considered age, lymph node involvement, tumor size, extracapsular extension, involved surgical margins, lymphovascular invasion, triple negative receptor status and multicentric presentation as major risk factors. Considering that after SSM and NSM, residual breast tissue can be left behind, the residual tissue considered as acceptable in the context of an oncologic surgery were 1-5 mm for breast surgeons. There is no consensus for the necessity of evaluating residual breast tissue through breast imaging. Conclusion: Although the indications of PORT after SSM and NSM vary among practitioners, standard risk factors for relapse are considered as important by radiation oncologists and breast surgeons.