Osimertinib plus Savolitinib to Overcome Acquired MET-Mediated Resistance in Epidermal Growth Factor Receptor-Mutated, MET-Amplified Non-Small Cell Lung Cancer: TATTONopen access
- Authors
- Hartmaier, RJ[Hartmaier, Ryan J.]; Markovets, AA[Markovets, Aleksandra A.]; Ahn, MJ[Ahn, Myung Ju]; Sequist, LV[Sequist, Lecia, V]; Han, JY[Han, Ji-Youn]; Cho, BC[Cho, Byoung Chul]; Yu, HA[Yu, Helena A.]; Kim, SW[Kim, Sang-We]; Yang, JCH[Yang, James Chih-Hsin]; Lee, JS[Lee, Jong-Seok]; Su, WC[Su, Wu-Chou]; Kowalski, DM[Kowalski, Dariusz M.]; Orlov, S[Orlov, Sergey]; Ren, S[Ren, Song]; Frewer, P[Frewer, Paul]; Ou, XL[Ou, Xiaoling]; Cross, DAE[Cross, Darren A. E.]; Kurian, N[Kurian, Nisha]; Cantarini, M[Cantarini, Mireille]; Janne, PA[Jaenne, Pasi A.]
- Issue Date
- Jan-2023
- Publisher
- AMER ASSOC CANCER RESEARCH
- Citation
- CANCER DISCOVERY, v.13, no.1, pp.98 - 113
- Indexed
- SCIE
SCOPUS
- Journal Title
- CANCER DISCOVERY
- Volume
- 13
- Number
- 1
- Start Page
- 98
- End Page
- 113
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/102608
- DOI
- 10.1158/2159-8290.CD-22-0586
- ISSN
- 2159-8274
- Abstract
- MET-inhibitor and EGFR tyrosine kinase inhibitor (EGFR-TKI) combination therapy could overcome acquired MET-mediated osimertinib resistance. We present the fi nal phase Ib TATTON (NCT02143466) analysis (Part B, n = 138/Part D, n= 42) assessing oral savolitinib 600 mg/300 mg once daily (q.d.) + osimertinib 80 mg q.d. in patients with MET-amplified, EGFR-mutated (EGFRm) advanced non-small cell lung cancer (NSCLC) and progression on prior EGFR-TKI. An accept-able safety profi le was observed. In Parts B and D, respectively, objective response rates were 33% to 67% and 62%, and median progression-free survival (PFS) was 5.5 to 11.1 months and 9.0 months. Increased antitumor activity may occur with MET copy number >= 10. EGFRm circulating tumor DNA clearance on treatment predicted longer PFS in patients with detectable baseline ctDNA, while acquired resistance mechanisms to osimertinib + savolitinib were mediated by MET, EGFR, or KRAS alterations. SIGNIFICANCE: The savolitinib + osimertinib combination represents a promising therapy in patients with MET-amplifi ed/overexpressed, EGFRm advanced NSCLC with disease progression on a prior EGFR-TKI. Acquired resistance mechanisms to this combination include those via MET, EGFR, and KRAS. On-treatment ctDNA dynamics can predict clinical outcomes and may provide an opportunity to inform earlier decision-making.
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Collections - Medicine > Department of Medicine > 1. Journal Articles
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