MAX SENNA MANO
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LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
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article BRAZILIAN DIRECTOR OF CARDIO-ONCOLOGY OF THE BRAZILIAN CARDIOLOGY SOCIETY ACHIEVEMENT(2011) KALIL FILHO, Roberto; HAJJAR, Ludhmila Abrahao; BACAL, Fernando; HOFF, Paulo Marcelo Gehm; DIZ, Maria Del Pilar Estevez; GALAS, Filomena Regina Barbosa Gomes; FUKUSHIMA, Julia Tizue; ALMEIDA, Juliano Pinheiro de; NAKAMURA, Rosana Ely; TRIELLI, Thalia Rodrigues; BITTAR, Cristina Salvadori; SANTOS, Marilia Harumi dos; GALDEANO, Flavia Gomes; AULER JUNIOR, Jose Otavio da Costa; SILVESTRINI, Anderson Arantes; ALENCAR, Aristoteles; MOTA, Augusto Cesar de Andrade; GUSMAO, Cid Abreu Buarque de; ALMEIDA, Dirceu Rodrigues; SIMOES, Claudia Marques; BOCCHI, Edimar Alcides; LIMA, Enaldo Melo de; FERNANDES, Fabio; SILVEIRA, Fabio Serra; VILAS-BOAS, Fabio; SILVA NETO, Luis Beck da; ROHDE, Luis Eduardo Paim; MONTERA, Marcelo Westerlund; BARBOSA, Marcia; MANO, Max Senna; RIECHELMANN, Rachel Simoes; ARAI, Roberto Jun; MARTINS, Silvia M.; FERREIRA, Silvia Moreira Ayub; SANTOS, Veronica- Return to work after breast cancer diagnosis: An observational prospective study in Brazil(2018) LANDEIRO, Luciana C. G.; GAGLIATO, Debora M.; FEDE, Angelo B.; FRAILE, Natalia M.; LOPEZ, Rossana M.; FONSECA, Leonardo G. da; PETRY, Vanessa; TESTA, Laura; HOFF, Paulo M.; MANO, Max S.Background In North America and Europe, return-to-work (RTW) rates vary among breast cancer (BC) survivors, from 24% to 66% and from 53% to 82% at 6 and 36 months after diagnosis, respectively. To date, there is a lack of data on RTW rates after BC diagnosis in Latin America. Therefore, the primary objectives of this study were to define RTW rates at 12 and 24 months after BC diagnosis and to identify the factors associated with RTW in this population. Methods In total, 125 employed women from a single institution with newly diagnosed BC were interviewed by telephone at 6, 12, and 24 months after diagnosis. Those who had inoperable or metastatic disease were excluded. Results Overall, RTW rates were 30.3% and 60.4% at 12 and 24 months after BC diagnosis, respectively. Most women reported that they received support from their employer, but only 29.1% reported having been offered work adjustments. In multivariate analysis, the factors associated with positive RTW outcomes included higher household income (odds ratio [OR], 17.76; 95% confidence interval [CI], 3.33-94.75; P = .001), breast-conserving surgery (OR, 9.77; 95% CI, 2.03-47.05; P = .004), and work adjustments (OR, 37.62; 95% CI, 2.03-47.05; P = .004). The factors associated with negative RTW outcomes included adjuvant endocrine therapy (OR, 0.11; 95% CI, 0.02-0.74; P = .023), and depression diagnosed after BC (OR, 0.07; 95% CI, 0.01-0.63; P = .017). Conclusions RTW rates in the current study were lower than those observed in developed countries but similar to the rates among low-income Americans. Workplace adjustments, higher income, breast-conserving surgery, endocrine therapy, and depression after BC played an important role in the RTW decision. Cancer 2018;124:4700-4710. (C) 2018 American Cancer Society.
- Effects of locoregional radiotherapy in patients with metastatic breast cancer(2016) MAURO, Geovanne Pedro; CARVALHO, Heloisa de Andrade; STUART, Silva Radwanski; MANO, Max Senna; MARTA, Gustavo NaderObjectives: This study aims to assess the clinical outcomes of patients with metastatic breast cancer (MBC) who underwent local radiation therapy (RT) for the primary site. Material and methods: Between 2005 and 2013, we retrospectively evaluated patients with MBC who received breast or chest wall RT with or without regional lymph node irradiation. Results: 2761 patients with breast cancer were treated with RT. Of them, 125 women with stage IV breast carcinoma were included. The median follow-up was 15 months (ranging from 3.8 to 168 months), when 54.7% of the patients had died; local progression was observed in 22.8% of the patients. The mean overall survival (OS) and local progression free survival (LoPFS) were 23.4 +/- 2.4 months and 45.1 +/- 2.9 months, respectively. Three-and five-year overall survival rates were, respectively, 21.2% and 13.3%. Local progression free survival was the same, 67.3%, at three and five years, respectively. Karnofsky Performance Status (KPS) (p = 0.015), number of metastatic sites (p = 0.031), RT dose (p = 0.0001) and hormone therapy (p = 0.0001) were confirmed as independent significant variables correlated with OS. The variables that were independently correlated with LoPFS were the number of previous chemotherapy lines (p = 0.038) and RT dose (p = 0.0001). Conclusion: RT of the primary site in patients with MBC is well tolerated. The factors that presented positive impact on survival were good KPS, low disease burden (1-3 metastatic sites), and the use of hormone therapy.
- 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
- A Phase II Randomized Study of Lapatinib Combined With Capecitabine, Vinorelbine, or Gemcitabine in Patients With HER2-Positive Metastatic Breast Cancer With Progression After a Taxane (Latin American Cooperative Oncology Group 0801 Study)(2016) GOMEZ, Henry L.; NECIOSUP, Silvia; TOSELLO, Celia; MANO, Max; BINES, Jose; ISMAEL, Gustavo; SANTI, Patricia X.; PINCZOWSKI, Helio; NERON, Yeni; FANELLI, Marcello; FEIN, Luis; SAMPAIO, Carlos; LERZO, Guillermo; CAPO, Adolfo; ZARBA, Juan J.; BLAJMAN, Cesar; VARELA, Mirta S.; MARTINEZ-MESA, Jeovany; WERUTSKY, Gustavo; BARRIOS, Carlos H.In LACOG 0801 phase II study 142 patients with HER2+ MBC with progression after taxane were randomized between Lapatinib (L) combined with Capecitabine (C), Vinorelbine (V) or Gemcitabine (G). ORR was 49% in LC, 56% in LV and 41% in LG group. The overall toxicity was manageable in all regimens. Background: Novel targeted agents and combinations have become available in multiple lines of treatment for human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC). In this context, alternatives to the lapatinib (L) and capecitabine (C) regimen, evaluating L combined with other cytotoxic drugs, are warranted. Patients and Methods: In the present phase II, multicenter study, patients with HER2+ MBC with progression after taxane were randomized between L, 1250 mg, combined with C, 2000 mg/m(2) on days 1 to 14 (LC), vinorelbine (V), 25 mg/m(2) on days 1 and 8 (LV), or gemcitabine (G), 1000 mg/m(2) on days 1 and 8 (LG), every 21 days. The primary endpoint was the overall response rate. Results: A total of 142 patients were included from 2009 to 2012. No differences were found in the patient baseline characteristics. The median age was 51 years, 69% were postmenopausal, 32% had liver metastasis, 57% were hormone receptor negative, and 48% had been previously treated with trastuzumab. The overall response rate was 49% (95% confidence interval [CI], 34.8%-63.4%), 56% (95% CI, 40%-70.4%), and 41% (95% CI, 27%-56.8%) in the LC, LV, and LG groups, respectively. The median progression-free survival was 9 months in the LC arm and 7 months in the other 2 arms (P = .28). The most common grade 3 and 4 adverse events were hand-foot syndrome (18%), diarrhea (6%), and increased alanine anninotransferase/aspartate aminotransferase (4%) in the LC arm; neutropenia (36%), diarrhea (9%), and febrile neutropenia (6%) in the LV arm; and neutropenia (47%), alanine aminotransferase/aspartate aminotransferase (13%), and rash (4%) in the LG arm. Conclusion: LV and LG seem to be active combinations in patients with HER2+ MBC after taxane failure. The overall toxicity was manageable in all regimens. (C) 2016 The Authors.
- 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.
- 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.
- 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.
- Patient-reported outcomes from KATHERINE: A phase 3 study of adjuvant trastuzumab emtansine versus trastuzumab in patients with residual invasive disease after neoadjuvant therapy for human epidermal growth factor receptor 2-positive breast cancer(2020) CONTE, PierFranco; SCHNEEWEISS, Andreas; LOIBL, Sibylle; MAMOUNAS, Eleftherios P.; MINCKWITZ, Gunter von; MANO, Max S.; UNTCH, Michael; HUANG, Chiun-Sheng; WOLMARK, Norman; RASTOGI, Priya; D'HONDT, Veronique; REDONDO, Andres; STAMATOVIC, Ljiljana; BONNEFOI, Herve; CASTRO-SALGUERO, Hugo; FISCHER, Hans H.; WAHL, Tanya; SONG, Chunyan; BOULET, Thomas; TRASK, Peter; GEYER JR., Charles E.Background The phase 3 KATHERINE trial demonstrated significantly improved invasive disease-free survival with adjuvant trastuzumab emtansine (T-DM1) versus trastuzumab in patients with HER2-positive early breast cancer and residual invasive disease after neoadjuvant chemotherapy plus HER2-targeted therapy. Methods Patients who received taxane- and trastuzumab-containing neoadjuvant therapy (with/without anthracyclines) and had residual invasive disease (breast and/or axillary nodes) at surgery were randomly assigned to 14 cycles of adjuvant T-DM1 (3.6 mg/kg intravenously every 3 weeks) or trastuzumab (6 mg/kg intravenously every 3 weeks). The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30) and breast cancer module (QLQ-BR23) were completed at screening, at day 1 of cycles 5 and 11, within 30 days after study drug completion, and at 6- and 12-month follow-up visits. Results Of patients who were randomly assigned to T-DM1 (n = 743) and trastuzumab (n = 743), 612 (82%) and 640 (86%), respectively, had valid baseline and >= 1 postbaseline assessments. No clinically meaningful changes (>= 10 points) from baseline in mean QLQ-C30 and QLQ-BR23 scores occurred in either arm. More patients receiving T-DM1 reported clinically meaningful deterioration at any assessment point in role functioning (49% vs 41%), appetite loss (38% vs 28%), constipation (47% vs 38%), fatigue (66% vs 60%), nausea/vomiting (39% vs 30%), and systemic therapy side effects (49% vs 36%). These differences were no longer apparent at the 6-month follow-up assessment, except for role functioning (23% vs 16%). Conclusion These data suggest that health-related quality of life was generally maintained in both study arms over the course of treatment.
- 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.