Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent or metastatic breast cancer (PERUSE)
T Bachelot, E Ciruelos, A Schneeweiss, F Puglisi, T Peretz-Yablonski, I Bondarenko, S Paluch-Shimon, A Wardley, J-L Merot, Y du Toit, V Easton, N Lindegger, D Miles, PERUSE investigators, Kamel Bouzid, Mario Campone, Bruno Coudert, Zbigniew Nowecki, Hassan Errihani, Florence Dalenc, Ana Ferreira, Max Mano, Francesco Ricci, Haralabos Kalofonos, Claudia Andreetta, Filippo Montemurro, Sophie Barrett, Qingyuan Zhang, Dimitris Mavroudis, Juan Matus, Carlos Beato, Xichun Hu, Rabab Gaafar, Hamdy Abdel Azeem, Christophe Perrin, Johannes Ettl, Istvan Lang, Sunil Verma, Huiping Li, Etienne Brain, Oliver Hoffmann, Anna Cariello, Carlo Tondini, Taher Altwegeiri, Niklas Loman, Michael Lux, Antonio Frassoldati, Zeba Aziz, Fernando Salas, Joanna Streb, Andrzej Wronski, Salomón Menjón Beltrán, Irfan Cicin, Peter Schmid, Robert Laing, Zhongsheng Tong, Katalin Boer, Balazs Juhasz, Luca Gianni, Giuseppe Curigliano, Alejandro Juarez, Snezana Susnjar, Erika Matos, Ruchan Uslu, Hans Wildiers, Marcelo Cruz, Hugues Bourgeois, Raquel von Schumann, Salomón Stemmer, Flavia Morales Vásquez, Adriana Dominguez, Marek Wojtukiewicz, Jasna Trifunovic, Jose Juan Illarramendi, Laura Garcia, Yann Izarzugaza Peron, Maria Jose Echarri, Natliia Voitko, Duncan Wheatley, Simon Waters, Richard De Boer, Guy Jerusalem, Véronique Cocquyt, Carlos Barrios, Lawrence Panasci, Johanna Mattson, Minna Tanner, Michel Gozy, Georgios Vasilopoulos, Janos Revesz, Luciano Latini, Cesare Gridelli, Jesus Lazaro, Antonio Gonzalez, Agusti Barnadas Molins, Eduardo Martinez, Jesús Alarcón, Ana Arance, Leif Klint, Oleksiy Kovalyov, Richard Baird, Belinda Yeo, Nicole McCarthy, Richard Greil, Shusen Wang, Xavier Artignan, Paule Augereau, Ingolf Juhasz-Boess, Roger Ngan, Hadassah Goldberg, Francesco Di Costanzo, Francesco Ferraù, Eduardas Aleknavicius, Kamran Rashid, Luís Costa, Jose Angel Garcia, Luis Ruiz de la Cruz, Rafael López López, Olga Del Val, Ozgur Ozyilkan, Fathi Azribi, Mark Verrill, Nicholas Turner, Jane Beith, Andreas Petzer, Jurandyr Andrade, Vanessa Bernstein, Daniel Rayson, Ibtessam Saad Eldin, Mihaëla Achille, Volkmar Mueller, Alessandra Gennari, Stefano Cascinu, Marwan Ghosn, Nagi El-Saghir, Joan Van den Bosch, Rianne Oosterkamp, Monika Kukulska, Ignacio Pelaez, Carolina Hernandez, Maria Del Mar Gordon, Elsa Dalmau, Jose Luis Alonso, Sercan Aksoy, Hasan Senol Coskun, Yaroslav Shparyk, Mohini Varughese, Udaiveer Panwar, Lisa Barraclough, Nicola Levitt, Jonathan Hicks, Anna Rigg, Mark Allen, Cecila Castillo, Luis Enrique Fein, Robin Stuart-Harris, Christian Singer, Herbert Stoeger, Sasha Smiljanic, Jifeng Feng, Miguel Cedeño, Jean Francois Berdah, Hubert Orfeuvre, Anthony Goncalves, Eva-Maria Grischke, Eike Simon, Steffen Wagner, Anna Efremidou, Konstantinos Papazisis, Ella Evron, Moshe Inbar, Noa Ben Baruch, David Geffen, Natalya Karminsky, Enzo Maria Ruggeri, Cavanna Luigi, Donatella Grasso, Elona Juozaityte, Jeronimo Rafael Rodriguez Cid, Henk Roerdink, Neelum Siddiqi, José Luís Passos Coelho, Elisa Garcia Garre, Andres Garcia, Noelia Martínez Jañez, Maria Helena Lopez Ceballos, Mireia Mele, María García, Alberto Arcediano, Karen McAdam, Timothy Perren, Jonathan Hicks, Wendy Taylor, Alison Humphreys, Raul Vera, Luis Alberto Kaen, Günther Steger, Johannes Andel, Jacques de Grève, Manon Huizing, Roberto Hegg, Anil Joy, Sandeep Sehdev, Riina Kütner, Johanna Ruohola, Nadine Dohollou, Jessica Grosjean, Philippe Laplaige, Rémy Largillier, Philippe Martin, Virginie Pottier, Jerome Alexandre, Bernd Christensen, Dirk-Michael Zahm, Fariba Khandan, Hans-Joachim Lueck, Georgios Fountzilas, Georgeta Fried, Alice Giacobino, Andrea Bonetti, Yanin Chavarri Guerra, Laurens Van Warmerdam, Annette Van der Velden, Suzan Vrijaldenhoven, Felix de Jongh, Milagros Cavero, Raquel Andres Conejero, Adolfo Murias, Salvador Saura, Amparo Oltra, Andres Redondo, Nuria Ribelles, Kilian Bachmeier, Johnathan Joffe, Prabir Chakraborti, Mark Beresford, Mohammad Butt, Christopher Poole, Gassan Yordi, Natasha Woodward, Gilberto Amorim, Nadia Califaretti, Susan Fox, Andre Robidoux, NanLi Li, Nenxiao Li, Jun Jiang, Tannia Soria, Peeter Padrik, Outi Saarni, Dominique Genet, Stéphanie Catala, Hugues Barletta, Luis Teixeira, Thomas Facchini, Tobias Hesse, Thorsten Kühn, Angelika Ober, Roland Repp, Willibald Schroeder, Dimitrios Pectasides, Gyorgy Bodoky, Zsuzsanna Kahan, Irina Jiveliouk, Ora Rosengarten, Oscar Alabiso, Mario Perez, Yes Van de Wouw, Jolanta Smok-Kalwat, Margarida Damasceno, Gabriela Sousa, Omalkhair Abulkhair, Antonio Antón Torres, Maria Purificación Martinez, Jesús Garcia Mata, Marta Santisteban Jesús Florián Jerico, Antonio Llombart, Rosa Sanchez, Juan Carlos Torrego, Clara Olier Garate, Cesar Rodriguez, Rosa Llorente, Diego Soto de Prado, Javier Cortés, Cristina Llorca, Antonio Galán, Gemma Viñas Villaro, Ulrik Narbe, Helena Granstam Bjömeklett, Sarah Westwell, Jackie Newby, Mariam Jafri, Robinson Rodríguez, Isabel Alonso, T Bachelot, E Ciruelos, A Schneeweiss, F Puglisi, T Peretz-Yablonski, I Bondarenko, S Paluch-Shimon, A Wardley, J-L Merot, Y du Toit, V Easton, N Lindegger, D Miles, PERUSE investigators, Kamel Bouzid, Mario Campone, Bruno Coudert, Zbigniew Nowecki, Hassan Errihani, Florence Dalenc, Ana Ferreira, Max Mano, Francesco Ricci, Haralabos Kalofonos, Claudia Andreetta, Filippo Montemurro, Sophie Barrett, Qingyuan Zhang, Dimitris Mavroudis, Juan Matus, Carlos Beato, Xichun Hu, Rabab Gaafar, Hamdy Abdel Azeem, Christophe Perrin, Johannes Ettl, Istvan Lang, Sunil Verma, Huiping Li, Etienne Brain, Oliver Hoffmann, Anna Cariello, Carlo Tondini, Taher Altwegeiri, Niklas Loman, Michael Lux, Antonio Frassoldati, Zeba Aziz, Fernando Salas, Joanna Streb, Andrzej Wronski, Salomón Menjón Beltrán, Irfan Cicin, Peter Schmid, Robert Laing, Zhongsheng Tong, Katalin Boer, Balazs Juhasz, Luca Gianni, Giuseppe Curigliano, Alejandro Juarez, Snezana Susnjar, Erika Matos, Ruchan Uslu, Hans Wildiers, Marcelo Cruz, Hugues Bourgeois, Raquel von Schumann, Salomón Stemmer, Flavia Morales Vásquez, Adriana Dominguez, Marek Wojtukiewicz, Jasna Trifunovic, Jose Juan Illarramendi, Laura Garcia, Yann Izarzugaza Peron, Maria Jose Echarri, Natliia Voitko, Duncan Wheatley, Simon Waters, Richard De Boer, Guy Jerusalem, Véronique Cocquyt, Carlos Barrios, Lawrence Panasci, Johanna Mattson, Minna Tanner, Michel Gozy, Georgios Vasilopoulos, Janos Revesz, Luciano Latini, Cesare Gridelli, Jesus Lazaro, Antonio Gonzalez, Agusti Barnadas Molins, Eduardo Martinez, Jesús Alarcón, Ana Arance, Leif Klint, Oleksiy Kovalyov, Richard Baird, Belinda Yeo, Nicole McCarthy, Richard Greil, Shusen Wang, Xavier Artignan, Paule Augereau, Ingolf Juhasz-Boess, Roger Ngan, Hadassah Goldberg, Francesco Di Costanzo, Francesco Ferraù, Eduardas Aleknavicius, Kamran Rashid, Luís Costa, Jose Angel Garcia, Luis Ruiz de la Cruz, Rafael López López, Olga Del Val, Ozgur Ozyilkan, Fathi Azribi, Mark Verrill, Nicholas Turner, Jane Beith, Andreas Petzer, Jurandyr Andrade, Vanessa Bernstein, Daniel Rayson, Ibtessam Saad Eldin, Mihaëla Achille, Volkmar Mueller, Alessandra Gennari, Stefano Cascinu, Marwan Ghosn, Nagi El-Saghir, Joan Van den Bosch, Rianne Oosterkamp, Monika Kukulska, Ignacio Pelaez, Carolina Hernandez, Maria Del Mar Gordon, Elsa Dalmau, Jose Luis Alonso, Sercan Aksoy, Hasan Senol Coskun, Yaroslav Shparyk, Mohini Varughese, Udaiveer Panwar, Lisa Barraclough, Nicola Levitt, Jonathan Hicks, Anna Rigg, Mark Allen, Cecila Castillo, Luis Enrique Fein, Robin Stuart-Harris, Christian Singer, Herbert Stoeger, Sasha Smiljanic, Jifeng Feng, Miguel Cedeño, Jean Francois Berdah, Hubert Orfeuvre, Anthony Goncalves, Eva-Maria Grischke, Eike Simon, Steffen Wagner, Anna Efremidou, Konstantinos Papazisis, Ella Evron, Moshe Inbar, Noa Ben Baruch, David Geffen, Natalya Karminsky, Enzo Maria Ruggeri, Cavanna Luigi, Donatella Grasso, Elona Juozaityte, Jeronimo Rafael Rodriguez Cid, Henk Roerdink, Neelum Siddiqi, José Luís Passos Coelho, Elisa Garcia Garre, Andres Garcia, Noelia Martínez Jañez, Maria Helena Lopez Ceballos, Mireia Mele, María García, Alberto Arcediano, Karen McAdam, Timothy Perren, Jonathan Hicks, Wendy Taylor, Alison Humphreys, Raul Vera, Luis Alberto Kaen, Günther Steger, Johannes Andel, Jacques de Grève, Manon Huizing, Roberto Hegg, Anil Joy, Sandeep Sehdev, Riina Kütner, Johanna Ruohola, Nadine Dohollou, Jessica Grosjean, Philippe Laplaige, Rémy Largillier, Philippe Martin, Virginie Pottier, Jerome Alexandre, Bernd Christensen, Dirk-Michael Zahm, Fariba Khandan, Hans-Joachim Lueck, Georgios Fountzilas, Georgeta Fried, Alice Giacobino, Andrea Bonetti, Yanin Chavarri Guerra, Laurens Van Warmerdam, Annette Van der Velden, Suzan Vrijaldenhoven, Felix de Jongh, Milagros Cavero, Raquel Andres Conejero, Adolfo Murias, Salvador Saura, Amparo Oltra, Andres Redondo, Nuria Ribelles, Kilian Bachmeier, Johnathan Joffe, Prabir Chakraborti, Mark Beresford, Mohammad Butt, Christopher Poole, Gassan Yordi, Natasha Woodward, Gilberto Amorim, Nadia Califaretti, Susan Fox, Andre Robidoux, NanLi Li, Nenxiao Li, Jun Jiang, Tannia Soria, Peeter Padrik, Outi Saarni, Dominique Genet, Stéphanie Catala, Hugues Barletta, Luis Teixeira, Thomas Facchini, Tobias Hesse, Thorsten Kühn, Angelika Ober, Roland Repp, Willibald Schroeder, Dimitrios Pectasides, Gyorgy Bodoky, Zsuzsanna Kahan, Irina Jiveliouk, Ora Rosengarten, Oscar Alabiso, Mario Perez, Yes Van de Wouw, Jolanta Smok-Kalwat, Margarida Damasceno, Gabriela Sousa, Omalkhair Abulkhair, Antonio Antón Torres, Maria Purificación Martinez, Jesús Garcia Mata, Marta Santisteban Jesús Florián Jerico, Antonio Llombart, Rosa Sanchez, Juan Carlos Torrego, Clara Olier Garate, Cesar Rodriguez, Rosa Llorente, Diego Soto de Prado, Javier Cortés, Cristina Llorca, Antonio Galán, Gemma Viñas Villaro, Ulrik Narbe, Helena Granstam Bjömeklett, Sarah Westwell, Jackie Newby, Mariam Jafri, Robinson Rodríguez, Isabel Alonso
Abstract
Background: 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.
Clinicaltrials.gov: NCT01572038.
Keywords: HER2-positive; dual HER2 blockade; first line; metastatic breast cancer; paclitaxel; pertuzumab.
© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Source: PubMed