Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC
Suresh S Ramalingam, Johan Vansteenkiste, David Planchard, Byoung Chul Cho, Jhanelle E Gray, Yuichiro Ohe, Caicun Zhou, Thanyanan Reungwetwattana, Ying Cheng, Busyamas Chewaskulyong, Riyaz Shah, Manuel Cobo, Ki Hyeong Lee, Parneet Cheema, Marcello Tiseo, Thomas John, Meng-Chih Lin, Fumio Imamura, Takayasu Kurata, Alexander Todd, Rachel Hodge, Matilde Saggese, Yuri Rukazenkov, Jean-Charles Soria, FLAURA Investigators, Michael Boyer, Chee Lee, Brett Hughes, Kenneth O'Byrne, Peter Briggs, Michael Milward, Thomas John, Ingel Demedts, Johan Vansteenkiste, Frédérique Bustin, Carlos Henrique Barrios, Constanta Timcheva, Charles Butts, Glenwood Goss, Rosalyn Juergens, Natasha Leighl, Susanna Cheng, Ronald Burkes, Parneet Cheema, Caicun Zhou, Helong Zhang, Yongqian Shu, Ying Cheng, 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, David Planchard, 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, Fumio Imamura, Yuichiro Ohe, Naoyuki Nogami, Toshiaki Takahashi, Takayasu Kurata, Kazuo Kasahara, Isamu Okamoto, Kiyotaka Yoh, Shunichi Sugawara, Nobuaki Kobayashi, Tsuneo Shimokawa, Chiyuki Okuda, Tatsuo Fukuhara, Masafumi Sata, Kazuhiko Nagakawa, Shinji Atagi, Yoshiro Nakahara, Byoung Chul Cho, Jong-Seok Lee, Kye Young Lee, Sang Won Shin, Ki Hyeong Lee, Eun Kyung Cho, Jin-Hyoung Kang, Soon Hin How, Pei Jye Voon, 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 Dois, 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, Wu-Chou Su, Busyamas Chewaskulong, Thanyanan Reungwetwattana, Vichien Srimuninnimit, Arunee Dechaphunkul, Sudsawat Laohavinij, Virote Sriuranpong, Ramazan Yildiz, Igor Bondarenko, Ihor Vynnychenko, Hryhoriy Adamchuk, Yaroslav Shparyk, Siow Ming Lee, Allan Price, Yvonne Summers, Riyaz Shah, Konstantin Dragnev, Ajit Maniam, Steven McCune, Jimmy Ruiz, Suresh Ramalingam, Pasi Jänne, Trevor Feinstein, John Hamm, Ian Anderson, Farrah Khan, Ralph Boccia, Jhanelle Gray, Ngoc Tran, Nhung Nguyen, Suresh S Ramalingam, Johan Vansteenkiste, David Planchard, Byoung Chul Cho, Jhanelle E Gray, Yuichiro Ohe, Caicun Zhou, Thanyanan Reungwetwattana, Ying Cheng, Busyamas Chewaskulyong, Riyaz Shah, Manuel Cobo, Ki Hyeong Lee, Parneet Cheema, Marcello Tiseo, Thomas John, Meng-Chih Lin, Fumio Imamura, Takayasu Kurata, Alexander Todd, Rachel Hodge, Matilde Saggese, Yuri Rukazenkov, Jean-Charles Soria, FLAURA Investigators, Michael Boyer, Chee Lee, Brett Hughes, Kenneth O'Byrne, Peter Briggs, Michael Milward, Thomas John, Ingel Demedts, Johan Vansteenkiste, Frédérique Bustin, Carlos Henrique Barrios, Constanta Timcheva, Charles Butts, Glenwood Goss, Rosalyn Juergens, Natasha Leighl, Susanna Cheng, Ronald Burkes, Parneet Cheema, Caicun Zhou, Helong Zhang, Yongqian Shu, Ying Cheng, 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, David Planchard, 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, Fumio Imamura, Yuichiro Ohe, Naoyuki Nogami, Toshiaki Takahashi, Takayasu Kurata, Kazuo Kasahara, Isamu Okamoto, Kiyotaka Yoh, Shunichi Sugawara, Nobuaki Kobayashi, Tsuneo Shimokawa, Chiyuki Okuda, Tatsuo Fukuhara, Masafumi Sata, Kazuhiko Nagakawa, Shinji Atagi, Yoshiro Nakahara, Byoung Chul Cho, Jong-Seok Lee, Kye Young Lee, Sang Won Shin, Ki Hyeong Lee, Eun Kyung Cho, Jin-Hyoung Kang, Soon Hin How, Pei Jye Voon, 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 Dois, 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, Wu-Chou Su, Busyamas Chewaskulong, Thanyanan Reungwetwattana, Vichien Srimuninnimit, Arunee Dechaphunkul, Sudsawat Laohavinij, Virote Sriuranpong, Ramazan Yildiz, Igor Bondarenko, Ihor Vynnychenko, Hryhoriy Adamchuk, Yaroslav Shparyk, Siow Ming Lee, Allan Price, Yvonne Summers, Riyaz Shah, Konstantin Dragnev, Ajit Maniam, Steven McCune, Jimmy Ruiz, Suresh Ramalingam, Pasi Jänne, Trevor Feinstein, John Hamm, Ian Anderson, Farrah Khan, Ralph Boccia, Jhanelle Gray, Ngoc Tran, Nhung Nguyen
Abstract
Background: Osimertinib is a third-generation, irreversible tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and EGFR T790M resistance mutations. A phase 3 trial compared first-line osimertinib with other EGFR-TKIs in patients with EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). The trial showed longer progression-free survival with osimertinib than with the comparator EGFR-TKIs (hazard ratio for disease progression or death, 0.46). Data from the final analysis of overall survival have not been reported.
Methods: In this trial, we randomly assigned 556 patients with previously untreated advanced NSCLC with an EGFR mutation (exon 19 deletion or L858R allele) in a 1:1 ratio to receive either osimertinib (80 mg once daily) or one of two other EGFR-TKIs (gefitinib at a dose of 250 mg once daily or erlotinib at a dose of 150 mg once daily, with patients receiving these drugs combined in a single comparator group). Overall survival was a secondary end point.
Results: The median overall survival was 38.6 months (95% confidence interval [CI], 34.5 to 41.8) in the osimertinib group and 31.8 months (95% CI, 26.6 to 36.0) in the comparator group (hazard ratio for death, 0.80; 95.05% CI, 0.64 to 1.00; P = 0.046). At 3 years, 79 of 279 patients (28%) in the osimertinib group and 26 of 277 (9%) in the comparator group were continuing to receive a trial regimen; the median exposure was 20.7 months and 11.5 months, respectively. Adverse events of grade 3 or higher were reported in 42% of the patients in the osimertinib group and in 47% of those in the comparator group.
Conclusions: Among patients with previously untreated advanced NSCLC with an EGFR mutation, those who received osimertinib had longer overall survival than those who received a comparator EGFR-TKI. The safety profile for osimertinib was similar to that of the comparator EGFR-TKIs, despite a longer duration of exposure in the osimertinib group. (Funded by AstraZeneca; FLAURA ClinicalTrials.gov number, NCT02296125.).
Copyright © 2019 Massachusetts Medical Society.
Source: PubMed