Alectinib in Resected ALK-Positive Non-Small-Cell Lung Cancer
Copyright © 2024 Massachusetts Medical Society..
BACKGROUND: Platinum-based chemotherapy is the recommended adjuvant treatment for patients with resectable, ALK-positive non-small-cell lung cancer (NSCLC). Data on the efficacy and safety of adjuvant alectinib as compared with chemotherapy in patients with resected ALK-positive NSCLC are lacking.
METHODS: We conducted a global, phase 3, open-label, randomized trial in which patients with completely resected, ALK-positive NSCLC of stage IB (tumors ≥4 cm), II, or IIIA (as classified according to the seventh edition of the Cancer Staging Manual of the American Joint Committee on Cancer and Union for International Cancer Control) were randomly assigned in a 1:1 ratio to receive oral alectinib (600 mg twice daily) for 24 months or intravenous platinum-based chemotherapy in four 21-day cycles. The primary end point was disease-free survival, tested hierarchically among patients with stage II or IIIA disease and then in the intention-to-treat population. Other end points included central nervous system (CNS) disease-free survival, overall survival, and safety.
RESULTS: In total, 257 patients were randomly assigned to receive alectinib (130 patients) or chemotherapy (127 patients). The percentage of patients alive and disease-free at 2 years was 93.8% in the alectinib group and 63.0% in the chemotherapy group among patients with stage II or IIIA disease (hazard ratio for disease recurrence or death, 0.24; 95% confidence interval [CI], 0.13 to 0.45; P<0.001) and 93.6% and 63.7%, respectively, in the intention-to-treat population (hazard ratio, 0.24; 95% CI, 0.13 to 0.43; P<0.001). Alectinib was associated with a clinically meaningful benefit with respect to CNS disease-free survival as compared with chemotherapy (hazard ratio for CNS disease recurrence or death, 0.22; 95% CI, 0.08 to 0.58). Data for overall survival were immature. No unexpected safety findings were observed.
CONCLUSIONS: Among patients with resected ALK-positive NSCLC of stage IB, II, or IIIA, adjuvant alectinib significantly improved disease-free survival as compared with platinum-based chemotherapy. (Funded by F. Hoffmann-La Roche; ALINA ClinicalTrials.gov number, NCT03456076.).
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:390 |
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| Enthalten in: |
The New England journal of medicine - 390(2024), 14 vom: 11. Apr., Seite 1265-1276 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wu, Yi-Long [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 12.04.2024 Date Revised 20.04.2024 published: Print ClinicalTrials.gov: NCT03456076 Citation Status MEDLINE |
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| doi: |
10.1056/NEJMoa2310532 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 500 | |a Date Revised 20.04.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a ClinicalTrials.gov: NCT03456076 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 Massachusetts Medical Society. | ||
| 520 | |a BACKGROUND: Platinum-based chemotherapy is the recommended adjuvant treatment for patients with resectable, ALK-positive non-small-cell lung cancer (NSCLC). Data on the efficacy and safety of adjuvant alectinib as compared with chemotherapy in patients with resected ALK-positive NSCLC are lacking | ||
| 520 | |a METHODS: We conducted a global, phase 3, open-label, randomized trial in which patients with completely resected, ALK-positive NSCLC of stage IB (tumors ≥4 cm), II, or IIIA (as classified according to the seventh edition of the Cancer Staging Manual of the American Joint Committee on Cancer and Union for International Cancer Control) were randomly assigned in a 1:1 ratio to receive oral alectinib (600 mg twice daily) for 24 months or intravenous platinum-based chemotherapy in four 21-day cycles. The primary end point was disease-free survival, tested hierarchically among patients with stage II or IIIA disease and then in the intention-to-treat population. Other end points included central nervous system (CNS) disease-free survival, overall survival, and safety | ||
| 520 | |a RESULTS: In total, 257 patients were randomly assigned to receive alectinib (130 patients) or chemotherapy (127 patients). The percentage of patients alive and disease-free at 2 years was 93.8% in the alectinib group and 63.0% in the chemotherapy group among patients with stage II or IIIA disease (hazard ratio for disease recurrence or death, 0.24; 95% confidence interval [CI], 0.13 to 0.45; P<0.001) and 93.6% and 63.7%, respectively, in the intention-to-treat population (hazard ratio, 0.24; 95% CI, 0.13 to 0.43; P<0.001). Alectinib was associated with a clinically meaningful benefit with respect to CNS disease-free survival as compared with chemotherapy (hazard ratio for CNS disease recurrence or death, 0.22; 95% CI, 0.08 to 0.58). Data for overall survival were immature. No unexpected safety findings were observed | ||
| 520 | |a CONCLUSIONS: Among patients with resected ALK-positive NSCLC of stage IB, II, or IIIA, adjuvant alectinib significantly improved disease-free survival as compared with platinum-based chemotherapy. (Funded by F. Hoffmann-La Roche; ALINA ClinicalTrials.gov number, NCT03456076.) | ||
| 650 | 4 | |a Clinical Trial, Phase III | |
| 650 | 4 | |a Comparative Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 7 | |a alectinib |2 NLM | |
| 650 | 7 | |a LIJ4CT1Z3Y |2 NLM | |
| 650 | 7 | |a Carbazoles |2 NLM | |
| 650 | 7 | |a Piperidines |2 NLM | |
| 650 | 7 | |a Receptor Protein-Tyrosine Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.10.1 |2 NLM | |
| 650 | 7 | |a ALK protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.10.1 |2 NLM | |
| 650 | 7 | |a Tyrosine Kinase Inhibitors |2 NLM | |
| 650 | 7 | |a Platinum Compounds |2 NLM | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 700 | 1 | |a Dziadziuszko, Rafal |e verfasserin |4 aut | |
| 700 | 1 | |a Ahn, Jin Seok |e verfasserin |4 aut | |
| 700 | 1 | |a Barlesi, Fabrice |e verfasserin |4 aut | |
| 700 | 1 | |a Nishio, Makoto |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Dae Ho |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Jong-Seok |e verfasserin |4 aut | |
| 700 | 1 | |a Zhong, Wenzhao |e verfasserin |4 aut | |
| 700 | 1 | |a Horinouchi, Hidehito |e verfasserin |4 aut | |
| 700 | 1 | |a Mao, Weimin |e verfasserin |4 aut | |
| 700 | 1 | |a Hochmair, Maximilian |e verfasserin |4 aut | |
| 700 | 1 | |a de Marinis, Filippo |e verfasserin |4 aut | |
| 700 | 1 | |a Migliorino, M Rita |e verfasserin |4 aut | |
| 700 | 1 | |a Bondarenko, Igor |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Shun |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Qun |e verfasserin |4 aut | |
| 700 | 1 | |a Ochi Lohmann, Tania |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Tingting |e verfasserin |4 aut | |
| 700 | 1 | |a Cardona, Andres |e verfasserin |4 aut | |
| 700 | 1 | |a Ruf, Thorsten |e verfasserin |4 aut | |
| 700 | 1 | |a Noe, Johannes |e verfasserin |4 aut | |
| 700 | 1 | |a Solomon, Benjamin J |e verfasserin |4 aut | |
| 700 | 0 | |a ALINA Investigators |e verfasserin |4 aut | |
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| 700 | 1 | |a Pavlakis, Nick |e investigator |4 oth | |
| 700 | 1 | |a Solomon, Benjamin J |e investigator |4 oth | |
| 700 | 1 | |a Burghuber, Otto |e investigator |4 oth | |
| 700 | 1 | |a Hochmair, Maximilian |e investigator |4 oth | |
| 700 | 1 | |a Beliakouski, Vasili |e investigator |4 oth | |
| 700 | 1 | |a Karchmit, Yauheniya |e investigator |4 oth | |
| 700 | 1 | |a Noryk, Dzmitry |e investigator |4 oth | |
| 700 | 1 | |a Ceric, Timur |e investigator |4 oth | |
| 700 | 1 | |a Chen, Chun |e investigator |4 oth | |
| 700 | 1 | |a Chen, Longqi |e investigator |4 oth | |
| 700 | 1 | |a Cheng, Ying |e investigator |4 oth | |
| 700 | 1 | |a Fu, Junke |e investigator |4 oth | |
| 700 | 1 | |a Liao, Yongde |e investigator |4 oth | |
| 700 | 1 | |a Lu, Shun |e investigator |4 oth | |
| 700 | 1 | |a Mao, Weimin |e investigator |4 oth | |
| 700 | 1 | |a Song, Pingping |e investigator |4 oth | |
| 700 | 1 | |a Wang, Qun |e investigator |4 oth | |
| 700 | 1 | |a Wu, Yi-Long |e investigator |4 oth | |
| 700 | 1 | |a Yang, Lin |e investigator |4 oth | |
| 700 | 1 | |a Zhao, Jun |e investigator |4 oth | |
| 700 | 1 | |a Zhong, Wenzhao |e investigator |4 oth | |
| 700 | 1 | |a Holmskov Hansen, Karin |e investigator |4 oth | |
| 700 | 1 | |a Kader, Yasser Abdel |e investigator |4 oth | |
| 700 | 1 | |a Barlesi, Fabrice |e investigator |4 oth | |
| 700 | 1 | |a Planchard, David |e investigator |4 oth | |
| 700 | 1 | |a Tomasini, Pascale |e investigator |4 oth | |
| 700 | 1 | |a Urban, Thierry |e investigator |4 oth | |
| 700 | 1 | |a Zalcman, Gerard |e investigator |4 oth | |
| 700 | 1 | |a Bischoff, Helge |e investigator |4 oth | |
| 700 | 1 | |a Hammerschmidt, Stefan |e investigator |4 oth | |
| 700 | 1 | |a Hoffknecht, Petra |e investigator |4 oth | |
| 700 | 1 | |a Rittmeyer, Achim |e investigator |4 oth | |
| 700 | 1 | |a Samantas, Epaminondas |e investigator |4 oth | |
| 700 | 1 | |a Tsiouda, Theodora |e investigator |4 oth | |
| 700 | 1 | |a Bittner, Nora |e investigator |4 oth | |
| 700 | 1 | |a Csoszi, Tibor |e investigator |4 oth | |
| 700 | 1 | |a Nagy, Tunde |e investigator |4 oth | |
| 700 | 1 | |a Daher, Sameh |e investigator |4 oth | |
| 700 | 1 | |a Gottfried, Maya |e investigator |4 oth | |
| 700 | 1 | |a Wollner, Mirjana |e investigator |4 oth | |
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| 700 | 1 | |a Migliorino, Maria Rita |e investigator |4 oth | |
| 700 | 1 | |a Novello, Silvia |e investigator |4 oth | |
| 700 | 1 | |a Piantedosi, Franco Vito |e investigator |4 oth | |
| 700 | 1 | |a Roila, Fausto |e investigator |4 oth | |
| 700 | 1 | |a Vitiello, Fabiana |e investigator |4 oth | |
| 700 | 1 | |a Daga, Haruko |e investigator |4 oth | |
| 700 | 1 | |a Fujiwara, Yutaka |e investigator |4 oth | |
| 700 | 1 | |a Goto, Koichi |e investigator |4 oth | |
| 700 | 1 | |a Hida, Toyoaki |e investigator |4 oth | |
| 700 | 1 | |a Horinouchi, Hidehito |e investigator |4 oth | |
| 700 | 1 | |a Ikeda, Norihiko |e investigator |4 oth | |
| 700 | 1 | |a Kato, Terufumi |e investigator |4 oth | |
| 700 | 1 | |a Kawamura, Tetsuji |e investigator |4 oth | |
| 700 | 1 | |a Kim, Young Hak |e investigator |4 oth | |
| 700 | 1 | |a Ko, Ryo |e investigator |4 oth | |
| 700 | 1 | |a Nakahara, Yasuharu |e investigator |4 oth | |
| 700 | 1 | |a Nishio, Makoto |e investigator |4 oth | |
| 700 | 1 | |a Oizumi, Satoshi |e investigator |4 oth | |
| 700 | 1 | |a Okada, Morihito |e investigator |4 oth | |
| 700 | 1 | |a Okamoto, Tatsuro |e investigator |4 oth | |
| 700 | 1 | |a Ono, Akira |e investigator |4 oth | |
| 700 | 1 | |a Sakagami, Takuro |e investigator |4 oth | |
| 700 | 1 | |a Seto, Takashi |e investigator |4 oth | |
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| 700 | 1 | |a Lee, Jong-Seok |e investigator |4 oth | |
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| 700 | 1 | |a Głogowski, Maciej |e investigator |4 oth | |
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| 700 | 1 | |a Polyakov, Igor |e investigator |4 oth | |
| 700 | 1 | |a Stroyakovskii, Daniil |e investigator |4 oth | |
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