Background: The phase III CLinical Evaluation Of Pertuzumab And TRAstuzumab (CLEOPATRA) trial established the combination of pertuzumab, trastuzumab and docetaxel as standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive locally recurrent/metastatic breast cancer (LR/mBC). The multicentre single-arm PERtUzumab global SafEty (PERUSE) study assessed the safety and efficacy of pertuzumab and trastuzumab combined with investigator-selected taxane in this setting. Patients and methods: Eligible patients with inoperable HER2-positive LR/mBC and no prior systemic therapy for LR/mBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Prespecified subgroup analyses included subgroups according to taxane, hormone receptor (HR) status and prior trastuzumab. Exploratory univariable analyses identified potential prognostic factors; those that remained significant in multivariable analysis were used to analyse PFS and OS in subgroups with all, some or none of these factors. Results: Of 1436 treated patients, 588 (41%) initially received paclitaxel and 918 (64%) had HR-positive disease. The most common grade ≥3 adverse events were neutropenia (10%, mainly with docetaxel) and diarrhoea (8%). At the final analysis (median follow-up: 5.7 years), median PFS was 20.7 [95% confidence interval (CI) 18.9-23.1] months overall and was similar irrespective of HR status or taxane. Median OS was 65.3 (95% CI 60.9-70.9) months overall. OS was similar regardless of taxane backbone but was more favourable in patients with HR-positive than HR-negative LR/mBC. In exploratory analyses, trastuzumab-pretreated patients with visceral disease had the shortest median PFS (13.1 months) and OS (46.3 months). Conclusions: Mature results from PERUSE show a safety and efficacy profile consistent with results from CLEOPATRA and median OS exceeding 5 years. Results suggest that paclitaxel is a valid alternative to docetaxel as backbone chemotherapy. Exploratory analyses suggest risk factors that could guide future trial design.

Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication / Miles, D.; Ciruelos, E.; Schneeweiss, A.; Puglisi, F.; Peretz-Yablonski, T.; Campone, M.; Bondarenko, I.; Nowecki, Z.; Errihani, H.; Paluch-Shimon, S.; Wardley, A.; Merot, J. -L.; Trask, P.; du Toit, Y.; Pena-Murillo, C.; Revelant, V.; Klingbiel, D.; Bachelot, T.; Bouzid, K.; Desmoulins, I.; Coudert, B.; Glogowska, I.; Ciruelos Gil, E.; Dalenc, F.; Ricci, F.; Dieras, V.; Kaufman, B.; Ferreira, A.; Mano, M.; Kalofonos, H.; Andreetta, C.; Montemurro, F.; Barrett, S.; Zhang, Q.; Mavroudis, D.; Matus, J.; Villarreal Garza, C.; Beato, C.; Ismael, G.; Hu, X.; Abdel Azeem, H.; Gaafar, R.; Perrin, C.; Kerbrat, P.; Ettl, J.; Paepke, S.; Hitre, E.; Lang, I.; Trudeau, M.; Verma, S.; Li, H.; Hoffmann, O.; Aktas, B.; Cariello, A.; Cruciani, G.; Tienghi, A.; Tondini, C.; Al-Twegieri, T.; Loman, N.; Laing, R.; Brain, E.; Fasching, P.; Lux, M.; Frassoldati, A.; Aziz, Z.; Salas, J.; Streb, J.; Krzemieniecki, K.; Wronski, A.; Garcia Garcia, J.; Menjon Beltran, S.; Cicin, I.; Schmid, P.; Gallagher, C.; Turner, N.; Tong, Z.; Boer, K.; Juhasz, B.; Horvath, Z.; Bianchini, G.; Gianni, L.; Curigliano, G.; Juarez Ramiro, A.; Susnjar, S.; Matos, E.; Sevillano, E.; Garcia Estevez, L.; Gokmen, E.; Uslu, R.; Wildiers, H.; Schutz, F.; Cruz, M.; Bourgeois, H.; von Schumann, R.; Stemmer, S.; Dominguez, A.; Morales-Vasques, F.; Wojtukiewicz, M.; Trifunovic, J.; Echarri Gonzalez, M. J.; Illarramendi Manas, J.; Martinez De Duenas, E.; Voitko, N.; Hicks, J.; Waters, S.; Barrett-Lee, P.; Wheatley, D.; De Boer, R.; Cocquyt, V.; Jerusalem, G.; Barrios, C.; Panasci, L.; Mattson, J.; Tanner, M.; Gozy, M.; Vasilopoulos, G.; Papandreou, C.; Revesz, J.; Battelli, N.; Benedetti, G.; Latini, L.; Gridelli, C.; Lazaro Leon, J.; Alarcon Company, J.; Arance Fernandez, A.; Barnadas Molins, A.; Calvo Plaza, I.; Bratos, R.; Gonzalez Martin, A.; Izarzugaza Peron, Y.; Klint, L.; Kovalev, A.; Mccarthy, N.; Yeo, B.; Kee, D.; Thomson, J.; White, S.; Greil, R.; Wang, S.; Artignan, X.; Juhasz-Boess, I.; Rody, A.; Ngan, R.; Dourleshter, F.; Goldberg, H.; Doni, L.; Di Costanzo, F.; Ferrau, F.; Drobniene, M.; Aleknavicius, E.; Rashid, K.; Costa, L.; de la Cruz Merino, L.; Garcia Saenz, J.; Lopez, R.; Del Val Munoz, O.; Ozyilkan, O.; Azribi, F.; Jaafar, H.; Baird, R.; Verrill, M.; Beith, J.; Petzer, A.; Moreira de Andrade, J.; Bernstein, V.; Macpherson, N.; Rayson, D.; Saad Eldin, I.; Achille, M.; Augereau, P.; Muller, V.; Rasco, A.; Evron, E.; Katz, D.; Berardi, R.; Cascinu, S.; De Censi, A.; Gennari, A.; El-Saghir, N.; Ghosn, M.; Oosterkamp, H. M.; Van den Bosch, J.; Kukulska, M.; Kalinka, E.; Alonso, J.; Dalmau Portulas, E.; Del Mar Gordon Santiago, M.; Pelaez Fernandez, I.; Aksoy, S.; Altundag, K.; Senol Coskun, H.; Bozcuk, H.; Shparyk, Y.; Barraclough, L.; Levitt, N.; Panwar, U.; Kelly, S.; Rigg, A.; Varughese, M.; Castillo, C.; Fein, L.; Malik, L.; Stuart-Harris, R.; Singer, C.; Stoeger, H.; Samonigg, H.; Feng, J.; Cedeno, M.; Ruohola, J.; Berdah, J. -F.; Goncalves, A.; Orfeuvre, H.; Grischke, E. -M.; Simon, E.; Wagner, S.; Koumakis, G.; Papazisis, K.; Ben Baruch, N.; Fried, G.; Geffen, D.; Karminsky, N.; Peretz, T.; Cavanna, L.; Pedrazzioli, P.; Grasso, D.; Ruggeri, E.; D'Auria, G.; Moscetti, L.; Juozaityte, E.; Rodriguez Cid, J.; Roerdink, H.; Siddiqi, N.; Passos Coelho, J.; Arcediano Del Amo, A.; Garcia Garre, E.; Garcia Gonzalez, M.; Garcia-Palomo Perez, A.; Herenandez Perez, C.; Lopez Alvarez, P.; Lopez De Ceballos, M. H.; Martinez Janez, N.; Mele Olive, M.; Mcadam, K.; Perren, T.; Dunn, G.; Humphreys, A.; Taylor, W.; Vera, R.; Kaen, L.; Andel, J.; Steger, G.; De Greve, J.; Huizing, M.; Hegg, R.; Joy, A.; Kuruvilla, P.; Sehdev, S.; Smiljanic, S.; Kutner, R.; Alexandre, J.; Grosjean, J.; Laplaige, P.; Largillier, R.; Maes, P.; Martin, P.; Pottier, V.; Christensen, B.; Khandan, F.; Luck, H. -J.; Zahm, D. -M.; Fountzilas, G.; Karavasilis, V.; Safra, T.; Inbar, M.; Ryvo, L.; Bonetti, A.; Seles, E.; Giacobino, A.; Chavarri Guerra, Y.; de Jongh, F.; van der Velden, A.; van Warmerdam, L.; Vrijaldenhoven, S.; Smorenburg, C. H.; Cavero, M.; Andres Conejero, R.; Oltra Ferrando, A.; Redondo Sanchez, A.; Ribelles Entrena, N.; Saura Grau, S.; Vinas Vilaro, G.; Bachmeier, K.; Beresford, M.; Butt, M.; Joffe, J.; Poole, C.; Woodings, P.; Chakraborti, P.; Yordi, G.; Woodward, N.; Nobre, A.; Luiz Amorim, G.; Califaretti, N.; Fox, S.; Robidoux, A.; Li, E.; Li, N.; Jiang, J.; Soria, T.; Padrik, P.; Lahdenpera, O.; Barletta, H.; Dohollou, N.; Genet, D.; Prulhiere, K.; Coeffic, D.; Facchini, T.; Vieillot, S.; Catala, S.; Teixeira, L.; Hesse, T.; Kuhn, T.; Ober, A.; Repp, R.; Schroder, W.; Pectasides, D.; Bodoky, G.; Kahan, Z.; Jiveliouk, I.; Rosengarten, O.; Rossi, V.; Alabiso, O.; Perez Martinez, M.; van de Wouw, A. J.; Smok-Kalwat, J.; Damasecno, M.; Augusto, I.; Sousa, G.; Saadein, A.; Abdelhafiez, N.; Abulkhair, O.; Anton Torres, A.; Corbellas Aparicio, M.; Llorente Domenech, R.; Florian Jerico, J.; Garcia Mata, J.; Gil Raga, M.; Galan Brotons, A.; Llombart Cussac, A.; Llorca Ferrandiz, C.; Martinez Del Prado, P.; Olier Garate, C.; Rodriguez Sanchez, C.; Sanchez Gomez, R.; Santisteban Eslava, M.; Soberino, J.; Vidal Losada Garcia, M.; Soto de Prado, D.; Torrego Garcia, J.; Vicente Rubio, E.; Garcia, M.; Murias Rosales, A.; Granstam Bjorneklett, H.; Narbe, U.; Jafri, M.; Rea, D.; Newby, J.; Jones, A.; Westwell, S.; Ring, A.; Alonso, I.; Rodriguez, R.. - In: ANNALS OF ONCOLOGY. - ISSN 0923-7534. - 32:10(2021), pp. 1245-1255. [10.1016/j.annonc.2021.06.024]

Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication

Berardi R.;
2021-01-01

Abstract

Background: The phase III CLinical Evaluation Of Pertuzumab And TRAstuzumab (CLEOPATRA) trial established the combination of pertuzumab, trastuzumab and docetaxel as standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive locally recurrent/metastatic breast cancer (LR/mBC). The multicentre single-arm PERtUzumab global SafEty (PERUSE) study assessed the safety and efficacy of pertuzumab and trastuzumab combined with investigator-selected taxane in this setting. Patients and methods: Eligible patients with inoperable HER2-positive LR/mBC and no prior systemic therapy for LR/mBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Prespecified subgroup analyses included subgroups according to taxane, hormone receptor (HR) status and prior trastuzumab. Exploratory univariable analyses identified potential prognostic factors; those that remained significant in multivariable analysis were used to analyse PFS and OS in subgroups with all, some or none of these factors. Results: Of 1436 treated patients, 588 (41%) initially received paclitaxel and 918 (64%) had HR-positive disease. The most common grade ≥3 adverse events were neutropenia (10%, mainly with docetaxel) and diarrhoea (8%). At the final analysis (median follow-up: 5.7 years), median PFS was 20.7 [95% confidence interval (CI) 18.9-23.1] months overall and was similar irrespective of HR status or taxane. Median OS was 65.3 (95% CI 60.9-70.9) months overall. OS was similar regardless of taxane backbone but was more favourable in patients with HR-positive than HR-negative LR/mBC. In exploratory analyses, trastuzumab-pretreated patients with visceral disease had the shortest median PFS (13.1 months) and OS (46.3 months). Conclusions: Mature results from PERUSE show a safety and efficacy profile consistent with results from CLEOPATRA and median OS exceeding 5 years. Results suggest that paclitaxel is a valid alternative to docetaxel as backbone chemotherapy. Exploratory analyses suggest risk factors that could guide future trial design.
2021
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11566/296693
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