Neoadjuvant Osimertinib for Resectable <i>EGFR</i> -Mutated Non–Small Cell Lung Cancer
Jianxing He, Masahiro Tsuboi, Walter Weder, Ke‐Neng Chen, Maximilian J. Hochmair, Jin‐Yuan Shih, Sung Yong Lee, Kang‐Yun Lee, Nguyen Viet Nhung, Somcharoen Saeteng, Lunxu Liu, Ligang Xing, Nguyen Hoang Gia, Shuji Murakami, Yong Han, María Paz Saavedra, Seong Hoon Yoon, Carlos Henrique Andrade Teixeira, Carles Escriu, Alex Martínez‐Martí, Collin M. Blakely, Yasushi Yatabe, Sanja Dacic, Yuri Rukazenkov, Xiangning Huang, Anupriya Dayal, Jamie E. Chaft, for the NeoADAURA Investigators, Gudrun Absenger, Maximilian J. Hochmair, Clarissa Baldotto, Georgia Fiuza Alencar Araripe, José Elias Miziara, José Fernando Bastos de Moura, Carlos H.A. Teixeira, Nataliya Chilingirova, Rossitza Krasteva, Velko Minchev, Marc de Perrot, Jonathan Spicer, Marcelo Garrido, Maria Paz Saavedra, Kaican Cai, Chang Chen, Ke‐Neng Chen, Qixun Chen, Chao Cheng, Duan Hongbing, Wentao Fang, Yong Han, Jianxing He, Gaofeng Li, Shanqing Li, Quan Lin, Lunxu Liu, Buhai Wang, Jingdi Wang, Qun Wang, Wenxiang Wang, Ming‐Hsun Wu, Nan Wu, Ligang Xing, Runxiang Yang, Bentong Yu, Wei Zhang, Jun Zhao, Ming Zhou, S. Galland-Girodet, Frank Griesinger, Justyna Rawluk, Wolfgang Schütte, Prabhat Singh Malik, Bhavesh Poladia, Jair Bar, Elizabeth Dudnik, Diego Cortinovis, Domenico Galetta, Silvia Novello, Sabrina Rossi, Norihiko Ikeda, Toshi Menju, Shuji Murakami, Morihito Okada, Jiro Okami, Akira Ono, Miyako Satouchi, Shunichi Sugawara, Hidemi Suzuki, Kazuya Takamochi, Hiroshi Tanaka, Masahiro Tsuboi, Yasuhiro Tsutani, Noriko Yanagitani, Yasushi Yatabe, Oscar Arrieta Rodriguez, Froylán López-López, Jerónimo Rodríguez Cid, Ana Fernandez, Jarosław Kołb-Sielecki, Jusang Kim
Abstract
PURPOSE Adjuvant osimertinib is the standard of care for patients with resected epidermal growth factor receptor ( EGFR )–mutated non–small cell lung cancer (NSCLC). Neoadjuvant treatment could improve surgical and long-term outcomes. METHODS In this randomized, controlled, phase III study, patients with resectable, EGFR -mutated, stage II-IIIB NSCLC were randomly assigned (1:1:1) to receive neoadjuvant osimertinib (80 mg orally once daily for ≥9 weeks) plus platinum-based chemotherapy (once every 3 weeks for three cycles), osimertinib monotherapy (for ≥9 weeks), or placebo plus platinum-based chemotherapy (control), followed by surgical resection. Adjuvant osimertinib was offered to eligible patients after completion of surgery. The primary end point was major pathologic response (MPR) by blinded central pathology review. Event-free survival (EFS) was a secondary end point. RESULTS Overall, 358 patients were randomly assigned to receive osimertinib plus chemotherapy (121 patients), osimertinib monotherapy (117 patients), or placebo plus chemotherapy (120 patients). Osimertinib plus chemotherapy (MPR rate 26%) and osimertinib monotherapy (25%) demonstrated statistically significant improvement in the MPR rate versus placebo plus chemotherapy (2%), with corresponding odds ratios of 19.82 (95.002% CI, 4.60 to 85.33; P < .0001) and 19.28 (99.9% CI, 1.71 to 217.39; P < .0001), respectively. With 15% data maturity, the EFS rates at 12 months were 93%, 95%, and 83% with osimertinib plus chemotherapy, osimertinib monotherapy, and placebo plus chemotherapy, respectively. In the neoadjuvant period, grade ≥3 adverse events of any cause occurred in 36%, 13%, and 33% of patients with osimertinib plus chemotherapy, osimertinib monotherapy, and placebo plus chemotherapy, respectively. No new safety concerns were identified. CONCLUSION Neoadjuvant osimertinib with or without chemotherapy demonstrated statistically significant improvement in the MPR rate over chemotherapy alone in patients with resectable, EGFR -mutated, stage II-IIIB NSCLC.