CNS Efficacy of Osimertinib With or Without Chemotherapy in Epidermal Growth Factor Receptor–Mutated Advanced Non–Small-Cell Lung Cancer-Reference-Cited by-同舟云学术

CNS Efficacy of Osimertinib With or Without Chemotherapy in Epidermal Growth Factor Receptor–Mutated Advanced Non–Small-Cell Lung Cancer

Published:2023-12-02 Issue: Volume: Page:
ISSN:0732-183X
Container-title:Journal of Clinical Oncology
language:en
Short-container-title:JCO

Author:

Jänne Pasi A.¹^ORCID,Planchard David²³^ORCID,Kobayashi Kunihiko⁴^ORCID,Cheng Ying⁵^ORCID,Lee Chee Khoon⁶^ORCID,Valdiviezo Natalia⁷^ORCID,Laktionov Konstantin⁸^ORCID,Yang Tsung-Ying⁹¹⁰,Yu Yan¹¹^ORCID,Kato Terufumi¹²^ORCID,Jiang Liyan¹³,Chewaskulyong Busyamas¹⁴^ORCID,Lucien Geater Sarayut¹⁵^ORCID,Maurel Jean-Marc¹⁶,Rojas Carlos¹⁷,Takahashi Toshiaki¹⁸^ORCID,Havel Libor¹⁹,Shepherd Frances A.²⁰,Tanaka Kentaro²¹^ORCID,Ghiorghiu Dana²²,Amin Neha P.²³^ORCID,Armenteros-Monterroso Elena²²,Huang Xiangning²⁴,Chaudhry Ammar Ahmed²³^ORCID,Yang James Chih-Hsin²⁵^ORCID

Affiliation:

1. Department of Medical Oncology, Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA

2. Department of Medical Oncology, Thoracic Group and International Center for Thoracic Cancers (CICT), Gustave Roussy, Villejuif, France

3. Faculty of Medicine, Paris-Saclay University, Paris, France

4. Department of Respiratory Medicine, Saitama Medical University International Medical Center, Hidaka, Japan

5. Department of Thoracic Oncology, Jilin Cancer Hospital, Changchun, China

6. Department of Medical Oncology, Cancer Care Centre, St George Hospital, Kogarah, NSW, Australia

7. Department of Oncology, Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru

8. Federal State Budgetary Institution “N.N.Blokhin National Medical Research Center of Oncology” of the Ministry of Health of the Russian Federation, Moscow, Russia

9. Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

10. Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan

11. Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China

12. Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Japan

13. Department of Respiratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China

14. Division of Oncology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand

15. Department of Internal Medicine, Prince of Songkla University, Songkhla, Thailand

16. Department of Clinical Oncology, Rondebosch Oncology Centre, Cape Town, South Africa

17. Medical Oncology Department, Bradford Hill Clinical Research Center, Santiago, Chile

18. Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan

19. First Faculty of Medicine, Charles University, Thomayer Hospital, Prague, Czech Republic

20. Department of Medical Oncology and Hematology, University Health Network, Princess Margaret Cancer Centre, Toronto, ON, Canada

21. Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

22. Late Development Oncology, AstraZeneca, Cambridge, United Kingdom

23. Late Development Oncology, AstraZeneca, Gaithersburg, MD

24. Department of Oncology Biometrics, AstraZeneca, Cambridge, United Kingdom

25. Department of Oncology, National Taiwan University Hospital and National Taiwan University Cancer Center, National Taiwan University, Taipei, Taiwan

Abstract

PURPOSE We report CNS efficacy of first-line osimertinib plus chemotherapy versus osimertinib monotherapy in patients with epidermal growth factor receptor ( EGFR)–mutated advanced non–small-cell lung cancer (NSCLC) from the phase III FLAURA2 study according to baseline CNS metastasis status. METHODS Patients were randomly assigned to osimertinib plus platinum-pemetrexed (combination) or osimertinib monotherapy until disease progression or discontinuation. Brain scans were performed in all patients at baseline and progression and at scheduled assessments until progression for patients with baseline CNS metastases; scans were assessed by neuroradiologist CNS blinded independent central review (BICR). RESULTS On the basis of baseline CNS BICR, 118 of 279 (combination) and 104 of 278 (monotherapy) randomly assigned patients had ≥one measurable and/or nonmeasurable CNS lesion and were included in the CNS full analysis set (cFAS); 40 of 118 and 38 of 104 had ≥one measurable target CNS lesion and were included in the post hoc CNS evaluable-for-response set (cEFR). In the cFAS, the hazard ratio (HR) for CNS progression or death was 0.58 (95% CI, 0.33 to 1.01). In patients without baseline CNS metastases, the HR for CNS progression or death was 0.67 (95% CI, 0.43 to 1.04). In the cFAS, CNS objective response rates (ORRs; 95% CI) were 73% (combination; 64 to 81) versus 69% (monotherapy; 59 to 78); 59% versus 43% had CNS complete response (CR). In the cEFR, CNS ORRs (95% CI) were 88% (73 to 96) versus 87% (72 to 96); 48% versus 16% had CNS CR. CONCLUSION Osimertinib plus platinum-pemetrexed demonstrated improved CNS efficacy compared with osimertinib monotherapy, including delaying CNS progression, irrespective of baseline CNS metastasis status. These data support this combination as a new first-line treatment for patients with EGFR-mutated advanced NSCLC, including those with CNS metastases.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

Link

https://ascopubs.org/doi/pdfdirect/10.1200/JCO.23.02219

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