Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer
Jean-Charles Soria, Yuichiro Ohe, Johan Vansteenkiste, Thanyanan Reungwetwattana, Busyamas Chewaskulyong, Ki Hyeong Lee, Arunee Dechaphunkul, Fumio Imamura, Naoyuki Nogami, Takayasu Kurata, Isamu Okamoto, Caicun Zhou, Byoung Chul Cho, Ying Cheng, Eun Kyung Cho, Pei Jye Voon, David Planchard, Wu-Chou Su, Jhanelle E Gray, Siow-Ming Lee, Rachel Hodge, Marcelo Marotti, Yuri Rukazenkov, Suresh S Ramalingam, FLAURA Investigators, Michael Boyer, Chee Lee, Brett Hughes, Kenneth O’Byrne, Peter Briggs, Michael Milward, Thomas John, Ingel Demedts, Frédérique Bustin, Carlos Henrique Barrios, Constanta Timcheva, Charles Butts, Glenwood Goss, Rosalyn Juergens, Natasha Leighl, Susanna Cheng, Ronald Burkes, Helong Zhang, Yongqian Shu, Qing Zhou, Wei Li, Guosheng Feng, Yong He, Buhai Wang, Hongjun Gao, Kejun Nan, Xiangdong Zhou, Yun Fan, Jian an Hunag, Yi Hu, Yun-Peng Liu, Chunling Liu, Yiping Zhang, Bo Zhu, Tomas Bartek, Isabelle Monnet, Claude El Kouri, Maurice Perol, Henri Berard, Jeannick Madelaine, Joachim von Pawel, Christian Grohe, Sabine Bohnet, Helge Bischoff, Christian Meyer zum Büschenfelde, Anja Rückert, Lazlo Urban, Zsolt Papi-Szekely, Eszter Csánky, Csaba Böcskei, Sándor Tehenes, Maya Gottfried, Jair Bar, Nir Peled, Mirjana Wollner, Alessandro Bertolini, Antonio Ardizzoia, Caterina Accettura, Michele Mitella, Rodolfo Passalacqua, Silvia Novello, Fausto Roila, Marcello Tiseo, Akimasa Sekine, Toshiaki Takahashi, Kazuo Kasahara, Kiyotaka Yoh, Shunichi Sugawara, Nobuaki Kobayashi, Tsuneo Shimokawa, Chiyuki Okuda, Tatsuo Fukuhara, Masafumi Sata, Kazuhiko Nagakawa, Shinji Atagi, Yoshiro Nakahara, Jong-Seok Lee, Kye Young Lee, Sang Won Shin, Jin-Hyoung Kang, Soon Hin How, Yong Kek Pang, Jemela Anne Osorio-Sanchez, Guia Elena Imelda Ladrera, Piotr Serwatowski, Aleksandra Szczesna, Katarzyna Zajda, Rodryg Ramlau, Dariusz Sawka, Maria Encarnação Teixeira, Teresa Almodovar, Marta Soares, Amélia Almeida, Ana Barroso, Michael Schenker, Alexandru Calin Girgorescu, Polixenia Iorga, Sergey Orlov, Nina Karaseva, Vladimir Moiseenko, Rosario Garcia Campelo, Maria Dolores Isla Casado, Manuel Cobo Dols, Ernest Nadal, Marc Campayo Guillaumes, Jose Luis González Larriba, Margarita Majem Tarruella, Sergio Vázquez Estévez, José Fuentes Pradera, Diego Márquez Medina, Anders Vikstrom, Oliver Gautschi, Christian Britschgi, Andreas Mueller, Ying-Huang Tsai, Ming-Fang Wu, Cheng-Ta Yang, Meng Chih Lin, Chao-Hsun Chen, Vichien Srimuninnimit, Sudsawat Laohavinij, Virote Sriuranpong, Ramazan Yildiz, Igor Bondarenko, Ihor Vynnychenko, Hryhoriy Adamchuk, Yaroslav Shparyk, Allan Price, Yvonne Summers, Riyaz Shah, Konstantin Dragnev, Ajit Maniam, Steven McCune, Jimmy Ruiz, Pasi Jänne, Trevor Feinstein, John Hamm, Ian Anderson, Farrah Khan, Ralph Boccia, Ngoc Tran, Nhung Nguyen, Jean-Charles Soria, Yuichiro Ohe, Johan Vansteenkiste, Thanyanan Reungwetwattana, Busyamas Chewaskulyong, Ki Hyeong Lee, Arunee Dechaphunkul, Fumio Imamura, Naoyuki Nogami, Takayasu Kurata, Isamu Okamoto, Caicun Zhou, Byoung Chul Cho, Ying Cheng, Eun Kyung Cho, Pei Jye Voon, David Planchard, Wu-Chou Su, Jhanelle E Gray, Siow-Ming Lee, Rachel Hodge, Marcelo Marotti, Yuri Rukazenkov, Suresh S Ramalingam, FLAURA Investigators, Michael Boyer, Chee Lee, Brett Hughes, Kenneth O’Byrne, Peter Briggs, Michael Milward, Thomas John, Ingel Demedts, Frédérique Bustin, Carlos Henrique Barrios, Constanta Timcheva, Charles Butts, Glenwood Goss, Rosalyn Juergens, Natasha Leighl, Susanna Cheng, Ronald Burkes, Helong Zhang, Yongqian Shu, Qing Zhou, Wei Li, Guosheng Feng, Yong He, Buhai Wang, Hongjun Gao, Kejun Nan, Xiangdong Zhou, Yun Fan, Jian an Hunag, Yi Hu, Yun-Peng Liu, Chunling Liu, Yiping Zhang, Bo Zhu, Tomas Bartek, Isabelle Monnet, Claude El Kouri, Maurice Perol, Henri Berard, Jeannick Madelaine, Joachim von Pawel, Christian Grohe, Sabine Bohnet, Helge Bischoff, Christian Meyer zum Büschenfelde, Anja Rückert, Lazlo Urban, Zsolt Papi-Szekely, Eszter Csánky, Csaba Böcskei, Sándor Tehenes, Maya Gottfried, Jair Bar, Nir Peled, Mirjana Wollner, Alessandro Bertolini, Antonio Ardizzoia, Caterina Accettura, Michele Mitella, Rodolfo Passalacqua, Silvia Novello, Fausto Roila, Marcello Tiseo, Akimasa Sekine, Toshiaki Takahashi, Kazuo Kasahara, Kiyotaka Yoh, Shunichi Sugawara, Nobuaki Kobayashi, Tsuneo Shimokawa, Chiyuki Okuda, Tatsuo Fukuhara, Masafumi Sata, Kazuhiko Nagakawa, Shinji Atagi, Yoshiro Nakahara, Jong-Seok Lee, Kye Young Lee, Sang Won Shin, Jin-Hyoung Kang, Soon Hin How, Yong Kek Pang, Jemela Anne Osorio-Sanchez, Guia Elena Imelda Ladrera, Piotr Serwatowski, Aleksandra Szczesna, Katarzyna Zajda, Rodryg Ramlau, Dariusz Sawka, Maria Encarnação Teixeira, Teresa Almodovar, Marta Soares, Amélia Almeida, Ana Barroso, Michael Schenker, Alexandru Calin Girgorescu, Polixenia Iorga, Sergey Orlov, Nina Karaseva, Vladimir Moiseenko, Rosario Garcia Campelo, Maria Dolores Isla Casado, Manuel Cobo Dols, Ernest Nadal, Marc Campayo Guillaumes, Jose Luis González Larriba, Margarita Majem Tarruella, Sergio Vázquez Estévez, José Fuentes Pradera, Diego Márquez Medina, Anders Vikstrom, Oliver Gautschi, Christian Britschgi, Andreas Mueller, Ying-Huang Tsai, Ming-Fang Wu, Cheng-Ta Yang, Meng Chih Lin, Chao-Hsun Chen, Vichien Srimuninnimit, Sudsawat Laohavinij, Virote Sriuranpong, Ramazan Yildiz, Igor Bondarenko, Ihor Vynnychenko, Hryhoriy Adamchuk, Yaroslav Shparyk, Allan Price, Yvonne Summers, Riyaz Shah, Konstantin Dragnev, Ajit Maniam, Steven McCune, Jimmy Ruiz, Pasi Jänne, Trevor Feinstein, John Hamm, Ian Anderson, Farrah Khan, Ralph Boccia, Ngoc Tran, Nhung Nguyen
Abstract
Background: Osimertinib is an oral, third-generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and EGFR T790M resistance mutations. We compared osimertinib with standard EGFR-TKIs in patients with previously untreated, EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC).
Methods: In this double-blind, phase 3 trial, we randomly assigned 556 patients with previously untreated, EGFR mutation-positive (exon 19 deletion or L858R) advanced NSCLC in a 1:1 ratio to receive either osimertinib (at a dose of 80 mg once daily) or a standard EGFR-TKI (gefitinib at a dose of 250 mg once daily or erlotinib at a dose of 150 mg once daily). The primary end point was investigator-assessed progression-free survival.
Results: The median progression-free survival was significantly longer with osimertinib than with standard EGFR-TKIs (18.9 months vs. 10.2 months; hazard ratio for disease progression or death, 0.46; 95% confidence interval [CI], 0.37 to 0.57; P<0.001). The objective response rate was similar in the two groups: 80% with osimertinib and 76% with standard EGFR-TKIs (odds ratio, 1.27; 95% CI, 0.85 to 1.90; P=0.24). The median duration of response was 17.2 months (95% CI, 13.8 to 22.0) with osimertinib versus 8.5 months (95% CI, 7.3 to 9.8) with standard EGFR-TKIs. Data on overall survival were immature at the interim analysis (25% maturity). The survival rate at 18 months was 83% (95% CI, 78 to 87) with osimertinib and 71% (95% CI, 65 to 76) with standard EGFR-TKIs (hazard ratio for death, 0.63; 95% CI, 0.45 to 0.88; P=0.007 [nonsignificant in the interim analysis]). Adverse events of grade 3 or higher were less frequent with osimertinib than with standard EGFR-TKIs (34% vs. 45%).
Conclusions: Osimertinib showed efficacy superior to that of standard EGFR-TKIs in the first-line treatment of EGFR mutation-positive advanced NSCLC, with a similar safety profile and lower rates of serious adverse events. (Funded by AstraZeneca; FLAURA ClinicalTrials.gov number, NCT02296125 .).
Source: PubMed