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.-.; 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.-.; Goncalves, A.; Orfeuvre, H.; Grischke, E.-.; 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.-.; Zahm, D.-.; 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.

doi:10.1016/j.annonc.2021.06.024

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

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.;X. Hu^{Membro del Collaboration Group};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.;G. Bianchini^{Membro del Collaboration Group};Gianni L.;G. Curigliano^{Membro del Collaboration Group};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.;L. Costa^{Membro del Collaboration Group};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.

2021

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.

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	Parole chiave
	
			HER2 positive; hormone receptor; metastatic breast cancer; overall survival; paclitaxel; pertuzumab; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Neoplasm Recurrence, Local; Receptor, ErbB-2; Taxoids; Trastuzumab; Treatment Outcome; Breast Neoplasms
		
	Settori scientifico-disciplinari dell'articolo
	
			Settore MED/06 - Oncologia Medica
		
	Data di pubblicazione
	
			ott-2021
		
	Rivista in ANCE
	
			ANNALS OF ONCOLOGY
		
	DOI
	
			https://dx.doi.org/10.1016/j.annonc.2021.06.024
		
	Tipologia
	
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			01 - Articolo su periodico

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