MAX SENNA MANO
Projetos de Pesquisa
Unidades Organizacionais
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
6 resultados
Resultados de Busca
Agora exibindo 1 - 6 de 6
- Adjuvant T-DM1 versus trastuzumab in patients with residual invasive disease after neoadjuvant therapy for HER2-positive breast cancer: subgroup analyses from KATHERINE(2021) MAMOUNAS, E. P.; UNTCH, M.; MANO, M. S.; HUANG, C-S; GEYER JR., C. E.; MINCKWITZ, G. von; WOLMARK, N.; PIVOT, X.; KUEMMEL, S.; DIGIOVANNA, M. P.; KAUFMAN, B.; KUNZ, G.; CONLIN, A. K.; ALCEDO, J. C.; KUEHN, T.; WAPNIR, I; FONTANA, A.; HACKMANN, J.; POLIKOFF, J.; SAGHATCHIAN, M.; BRUFSKY, A.; YANG, Y.; ZIMOVJANOVA, M.; BOULET, T.; LIU, H.; TESAROWSKI, D.; LAM, L. H.; SONG, C.; SMITT, M.; LOIBL, S.Y Background: In the KATHERINE study (NCT01772472), patients with residual invasive early breast cancer (EBC) after neoadjuvant chemotherapy (NACT) plus human epidermal growth factor receptor 2 (HER2)-targeted therapy had a 50% reduction in risk of recurrence or death with adjuvant trastuzumab emtansine (T-DM1) versus trastuzumab. Here, we present additional exploratory safety and efficacy analyses. Patients and methods: KATHERINE enrolled HER2-positive EBC patients with residual invasive disease in the breast/ axilla at surgery after NACT containing a taxane (+/- anthracycline, +/- platinum) and trastuzumab (+/- pertuzumab). Patients were randomized to adjuvant T-DM1 (n = 743) or trastuzumab (n = 743) for 14 cycles. The primary endpoint was invasive disease-free survival (IDFS). Results: The incidence of peripheral neuropathy (PN) was similar regardless of neoadjuvant taxane type. Irrespective of treatment arm, baseline PN was associated with longer PN duration (median, 105-109 days longer) and lower resolution rate (w65% versusw82%). Prior platinum therapy was associated with more grade 3-4 thrombocytopenia in the TDM1 arm (13.5% versus 3.8%), but there was no grade >3 hemorrhage in these patients. Risk of recurrence or death was decreased with T-DM1 versus trastuzumab in patients who received anthracycline-based NACT [hazard ratio (HR) = 0.51; 95% confidence interval (CI): 0.38-0.67], non-anthracycline-based NACT (HR = 0.43; 95% CI: 0.220.82), presented with cT1, cN0 tumors (0 versus 6 IDFS events), or had particularly high-risk tumors (HRs ranged from 0.43 to 0.72). The central nervous system (CNS) was more often the site of first recurrence in the T-DM1 arm (5.9% versus 4.3%), but T-DM1 was not associated with a difference in overall risk of CNS recurrence. Conclusions: T-DM1 provides clinical benefit across patient subgroups, including small tumors and particularly high-risk tumors and does not increase the overall risk of CNS recurrence. NACT type had a minimal impact on safety.
conferenceObject THE ENCHANTTM TRIAL: AN OPEN LABEL MULTICENTER PHASE 2 WINDOW OF OPPORTUNITY STUDY EVALUATING GANETESPIB (STA-9090) MONOTHERAPY IN WOMEN WITH PREVIOUSLY UNTREATED METASTATIC HER2 POSITIVE OR TRIPLE NEGATIVE BREAST CANCER (TNBC)(2012) CAMERON, D.; MANO, M. S.; VUKOVIC, V.; TEOFILOVICI, F.; BRADLEY, R.; AWADA, A.Background Hsp90 is a molecular chaperone required for proper folding and activation of many cancer-promoting proteins. Several Hsp90 clients are oncoproteins known to play a key role in the pathobiology of breast cancer, including HER2, p95-HER2, EGFR, ER, PI3K, AKT, and VEGFR. The inactivation of these oncoproteins by Hsp90 inhibition is a promising approach for breast cancer therapy. Ganetespib is an Hsp90 inhibitor which has shown anti-tumor activity in heavily pretreated patients with lung, breast, and other cancers. Ganetespib is well tolerated without severe liver or common ocular toxicities. In a phase 2 trial, 22 breast cancer patients who had received up to 3 prior lines of chemotherapy including trastuzumab were treated with ganetespib monotherapy. In patients with HER2+ disease, the objective response rate (ORR) was 15% (2/13) and the SD rate was 46% (6/13). Only 3 patients presented with TNBC; one of those patients achieved SD with substantial tumor shrinkage on treatment. Methods This is a single arm international open-label Phase 2 study in patients with HER2 amplified, or triple negative breast cancer. Patients must not have received any prior therapy in the metastatic setting. Prior adjuvant therapy is allowed. Primary endpoint: ORR. Main secondary endpoints include disease control rate, and progression free survival. Additionally, fresh biopsies and serum samples are collected from all patients for determination of predictors of response and mechanisms of resistance to treatment. Patients are treated with ganetespib 150 mg/m2 is given twice weekly of a 4-week cycle for up to 12 weeks. A total of 70 patients are planned for accrual. At the time of submission, the study is receiving IRB approvals in several centers.- 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.
conferenceObject Peripheral neuropathy (PN), thrombocytopenia (TCP) and central nervous system (CNS) recurrence: An update of the phase III KATHERINE trial of post-neoadjuvant trastuzumab emtansine (T-DM1) or trastuzumab (H) in patients (pts) with residual invasive HER2-positive breast cancer (BC)(2019) UNTCH, M.; GEYER JR., C. E.; HUANG, C.; LOIBL, S.; WOLMARK, N.; MANO, M. S.; MINCKWITZ, G. von; BRUFSKY, A.; PIVOT, X.; POLIKOFF, J.; FONTANA, A.; KAUFMAN, B.; ALCEDO, J. C.; BOULET, T.; LIU, H.; SONG, C.; MAMOUNAS, E. P.conferenceObject CARDIAC SAFETY OF (NEO) ADJUVANT TRASTUZUMAB IN THE BRAZILIAN COMMUNITY SETTING: A SINGLE CENTER EXPERIENCE(2012) FONSECA, L. G.; TAKAHASHI, T. K.; MAK, M. P.; BARROSO-SOUSA, R.; TESTA, L.; HELENA, V. Petry; COSTA, R. De Paula; HOFF, P. M.; MANO, M. S.Background Trastuzumab-associated cardiotoxicity (TAC) has been established in the context of clinical trials. However, when newly registered agents are used in a broader patient population, their safety profile does not always mirror that of the pivotal trials. Trastuzumab (T) only became available in the Brazilian public sector in 2008 and herein we report our off-trial experience so far. Methods Retrospective, single center cohort of HER-2 positive breast cancer patients (pts) treated with (neo)adjuvant chemotherapy and T from July 2008 to March 2012. 95.3% were treated according to local protocol (11.4% TCH; 83.9% AC-TH). Major cardiac event (MCE) was defined as a left ventricular ejection fraction (LVEF) drop of 10% and absolute drop to < 50 % by echocardiogram (ECHO) or as symptomatic heart failure (HF) regardless of the LVEF value or any cardiac event considered clinically meaningful. A multivariable Cox proportional hazards model was used to control for other cardiac risk factors. Results 237 women were identified: median age 53 y (27-83), 99.6% ECOG-PS 0-1, median body mass index 27.4 kg/m2 (17 – 46), 30.4% had hypertension (HTN), 8.8% had diabetes mellitus (DM), 5.9% had previous cardiopathy. 54.8% had ER-positive tumors; 40.7% received neoadjuvant T; most were stage II or III (22.3% and 37.1%). Median number of ECHO assessments was 2.7 (0-6); 136 pts (57.2%) completed T as planned. 20.2% had MCE (13.9% discontinued T). 3.8% discontinued T due to symptomatic HF and 5% for non-cardiac reasons. 41.6% of MCE pts recovered cardiac function. Median initial LVEF was 64.83 ± 1.5 % (no event) vs 64.81 ± 1.5 % (MCE) p = 0.26; median 3-month LFVE was 64.67 ± 4 % (no event) vs 56.12 ± 3 % (MCE) p = 0.0036. HTN, DM, obesity, age, radiotherapy, use of anthracycline and previous cardiopathy were not significantly associated with TAC. Conclusions Our results suggest that TAC in our routine practice is slightly higher than reported in literature (6 to 17%), possibly reflecting selection bias in clinical trials. Symptomatic TAC was as expected for AC-TH (4%). We failed to identify risk factors for TAC, possibly due to the low number of events. Cardiac function must be closely monitored during T treatment and careful pt selection is crucial.conferenceObject Peripheral neuropathy (PN), thrombocytopenia (TCP) and central nervous system (CNS) recurrence: An update of the phase III KATHERINE trial of post-neoadjuvant trastuzumab emtansine (T-DM1) or trastuzumab (H) in patients (pts) with residual invasive HER2-positive breast cancer (BC)(2019) UNTCH, M.; GEYER, C. E.; HUANG, C.; LOIBL, S.; WOLMARK, N.; MANO, M. S.; MINCKWITZ, G. von; BRUFSKY, A.; PIVOT, X.; POLIKOFF, J.; FONTANA, A.; KAUFMAN, B.; ALCEDO, J. C.; BOULET, T.; LIU, H.; SONG, C.; MAMOUNAS, E. P.