Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer
José Baselga, Javier Cortés, Sung-Bae Kim, Seock-Ah Im, Roberto Hegg, Young-Hyuck Im, Laslo Roman, José Luiz Pedrini, Tadeusz Pienkowski, Adam Knott, Emma Clark, Mark C Benyunes, Graham Ross, Sandra M Swain, CLEOPATRA Study Group, M A Bártoli, M I Bianconi, M Kotliar, J A Lacava, M Matwiejuk, P E Price, M Varela, J Andrade, R Araujo, S Azevedo, E Cortes, E Costa e Silva, D Cubero, G Delgado, M del P Diz, B Eyll, F Franke, R Hegg, G Ismael, D Jendiroba, J L Pedrini, R Pereira, H Pinczowski, P Tokunaga, C Tosello, C Brezden-Masley, Ying Cheng, Xuenong Ouyang, Zhenzhou Shen, Xiaojia Wang, Liwei Wang, Tsz Kok Yau, W Yeo, D Otero, Z Soldic, D Vrbanec, T Soria, P Kellokumpu-Lehtinen, S Pyrhönen, M Campone, B Coudert, J M Ferrero, F Priou, B Aktas, W Aulitzky, M Clemens, E-M Grischke, M Hauschild, M Just, A Kirsch, S Kuemmel, C Maintz, A Marmé, V Mueller, M Schmidt, A Schneeweiss, C Schumacher, C Thomssen, B Wesenberg, H Castro-Salguero, C Hernandez Monroy, L M Zelina-Toache, D Amadori, C Angiolini, L Biganzoli, S Cinieri, T Gamucci, S Iacobelli, L Latini, F Montemurro, E Simoncini, K Aogi, H Fuji, J Horiguchi, K Inoue, Y Ito, H Iwata, M Kashiwaba, N Kohno, K Kuroi, N Masuda, K Nakagami, T Nakayama, R Nishimura, S Saji, Y Sasaki, N Sato, K Takeda, Y Tokuda, K Tsugawa, T Ueno, J Watanabe, R Yoshiaki, Seock-Ah Im, Young-Hyuck Im, Sung Bae Kim, Yong Wha Moon, Jung Sil Ro, Joo Hyuk Sohn, E Grincuka, I Kudaba, G Purkalne, L Kostovska-Maneva, P Stefanovski, G Martinez, G Tellez, P Caguioa, V Chan, D Tudtud, M Foszczynska-Kloda, T Pienkowski, W Polkowski, E Starowsławska, P Tomczak, V Gorbunova, E Gotovkin, I Kiselev, M Kopp, M Lichinitser, V Merkulov, L Roman, V Semiglazov, V Shirinkin, Soo Chin Lee, Zee Wan Wong, E Alba Conejo, J Baselga, N Batista, L Calvo, E Ciruelos, J Cortés, M Gil i Gil, A Gonzalez, J Hornedo Muguiro, S Morales, N Ribelles Entrena, S De la C Sánchez, P Sanchez Rovira, W Arpornwirat, T Dejthevaporn, J Maneechavakajorn, V Srimuninnimit, V Sriuranpong, P Sunpaweravong, R Ahmad, L Assersohn, I Boiangiu, N Davidson, C Gallagher, A Jones, D Miles, S O'Reilly, A Robinson, D Wheatley, R Agajanian, J F Armor, M W Audeh, A S Behairy, R Birhiray, R Blachly, K Blackwell, R Blanchard, P Blanchet, B J Bowers, A Brufsky, L Budde, R R Carroll, V Charu, S Dakhil, B Daniel, J A Ellerton, L Fehrenbacher, P Flynn, S Franco, N Green, V Hansen, J Hargis, C Hendricks, R C Hermann, A Kallab, M Karwal, G Kato, P Kaufman, P S Kennedy, P Klein, E P Lester, C F Lobo, R A Michaelson, J A Neidhart, J D Neidhart, A D Nguyen, T O'Rourke, R Patel, T Patel, A Perez, J A Quackenbush, C E Peterson, J D Polikoff, S J Prill, R Robles, G Rodriguez, F Senecal, P Sharma, R Smith, D Spicer, S A Swain, J A Taguchi, C L Vogel, D M Waterhouse, S Yadav, D A Yardley, José Baselga, Javier Cortés, Sung-Bae Kim, Seock-Ah Im, Roberto Hegg, Young-Hyuck Im, Laslo Roman, José Luiz Pedrini, Tadeusz Pienkowski, Adam Knott, Emma Clark, Mark C Benyunes, Graham Ross, Sandra M Swain, CLEOPATRA Study Group, M A Bártoli, M I Bianconi, M Kotliar, J A Lacava, M Matwiejuk, P E Price, M Varela, J Andrade, R Araujo, S Azevedo, E Cortes, E Costa e Silva, D Cubero, G Delgado, M del P Diz, B Eyll, F Franke, R Hegg, G Ismael, D Jendiroba, J L Pedrini, R Pereira, H Pinczowski, P Tokunaga, C Tosello, C Brezden-Masley, Ying Cheng, Xuenong Ouyang, Zhenzhou Shen, Xiaojia Wang, Liwei Wang, Tsz Kok Yau, W Yeo, D Otero, Z Soldic, D Vrbanec, T Soria, P Kellokumpu-Lehtinen, S Pyrhönen, M Campone, B Coudert, J M Ferrero, F Priou, B Aktas, W Aulitzky, M Clemens, E-M Grischke, M Hauschild, M Just, A Kirsch, S Kuemmel, C Maintz, A Marmé, V Mueller, M Schmidt, A Schneeweiss, C Schumacher, C Thomssen, B Wesenberg, H Castro-Salguero, C Hernandez Monroy, L M Zelina-Toache, D Amadori, C Angiolini, L Biganzoli, S Cinieri, T Gamucci, S Iacobelli, L Latini, F Montemurro, E Simoncini, K Aogi, H Fuji, J Horiguchi, K Inoue, Y Ito, H Iwata, M Kashiwaba, N Kohno, K Kuroi, N Masuda, K Nakagami, T Nakayama, R Nishimura, S Saji, Y Sasaki, N Sato, K Takeda, Y Tokuda, K Tsugawa, T Ueno, J Watanabe, R Yoshiaki, Seock-Ah Im, Young-Hyuck Im, Sung Bae Kim, Yong Wha Moon, Jung Sil Ro, Joo Hyuk Sohn, E Grincuka, I Kudaba, G Purkalne, L Kostovska-Maneva, P Stefanovski, G Martinez, G Tellez, P Caguioa, V Chan, D Tudtud, M Foszczynska-Kloda, T Pienkowski, W Polkowski, E Starowsławska, P Tomczak, V Gorbunova, E Gotovkin, I Kiselev, M Kopp, M Lichinitser, V Merkulov, L Roman, V Semiglazov, V Shirinkin, Soo Chin Lee, Zee Wan Wong, E Alba Conejo, J Baselga, N Batista, L Calvo, E Ciruelos, J Cortés, M Gil i Gil, A Gonzalez, J Hornedo Muguiro, S Morales, N Ribelles Entrena, S De la C Sánchez, P Sanchez Rovira, W Arpornwirat, T Dejthevaporn, J Maneechavakajorn, V Srimuninnimit, V Sriuranpong, P Sunpaweravong, R Ahmad, L Assersohn, I Boiangiu, N Davidson, C Gallagher, A Jones, D Miles, S O'Reilly, A Robinson, D Wheatley, R Agajanian, J F Armor, M W Audeh, A S Behairy, R Birhiray, R Blachly, K Blackwell, R Blanchard, P Blanchet, B J Bowers, A Brufsky, L Budde, R R Carroll, V Charu, S Dakhil, B Daniel, J A Ellerton, L Fehrenbacher, P Flynn, S Franco, N Green, V Hansen, J Hargis, C Hendricks, R C Hermann, A Kallab, M Karwal, G Kato, P Kaufman, P S Kennedy, P Klein, E P Lester, C F Lobo, R A Michaelson, J A Neidhart, J D Neidhart, A D Nguyen, T O'Rourke, R Patel, T Patel, A Perez, J A Quackenbush, C E Peterson, J D Polikoff, S J Prill, R Robles, G Rodriguez, F Senecal, P Sharma, R Smith, D Spicer, S A Swain, J A Taguchi, C L Vogel, D M Waterhouse, S Yadav, D A Yardley
Abstract
Background: The anti-human epidermal growth factor receptor 2 (HER2) humanized monoclonal antibody trastuzumab improves the outcome in patients with HER2-positive metastatic breast cancer. However, most cases of advanced disease eventually progress. Pertuzumab, an anti-HER2 humanized monoclonal antibody that inhibits receptor dimerization, has a mechanism of action that is complementary to that of trastuzumab, and combination therapy with the two antibodies has shown promising activity and an acceptable safety profile in phase 2 studies involving patients with HER2-positive breast cancer.
Methods: We randomly assigned 808 patients with HER2-positive metastatic breast cancer to receive placebo plus trastuzumab plus docetaxel (control group) or pertuzumab plus trastuzumab plus docetaxel (pertuzumab group) as first-line treatment until the time of disease progression or the development of toxic effects that could not be effectively managed. The primary end point was independently assessed progression-free survival. Secondary end points included overall survival, progression-free survival as assessed by the investigator, the objective response rate, and safety.
Results: The median progression-free survival was 12.4 months in the control group, as compared with 18.5 months in the pertuzumab group (hazard ratio for progression or death, 0.62; 95% confidence interval, 0.51 to 0.75; P<0.001). The interim analysis of overall survival showed a strong trend in favor of pertuzumab plus trastuzumab plus docetaxel. The safety profile was generally similar in the two groups, with no increase in left ventricular systolic dysfunction; the rates of febrile neutropenia and diarrhea of grade 3 or above were higher in the pertuzumab group than in the control group.
Conclusions: The combination of pertuzumab plus trastuzumab plus docetaxel, as compared with placebo plus trastuzumab plus docetaxel, when used as first-line treatment for HER2-positive metastatic breast cancer, significantly prolonged progression-free survival, with no increase in cardiac toxic effects. (Funded by F. Hoffmann-La Roche/Genentech; ClinicalTrials.gov number, NCT00567190.).
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Source: PubMed