Overcoming Acquired MET-Driven Resistance to First-Line Lorlatinib: Successful Combination of Lorlatinib and Envafolimab in an ALK-Positive NSCLC Patient with Ultra-High PD-L1 Expression.
Simple Summary: Targeted therapy has significantly improved outcomes for patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC); however, the emergence of resistance remains an inevitable clinical challenge. Standard treatment after progression on third-generation...
| Publicado en: | Current Oncology Vol. 33; no. 5; pp. 258 - 268 |
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| Autores principales: | , , , , |
| Formato: | Journal Article |
| Publicado: |
MDPI
May2026
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=194129130&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 194129130 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 11980052 5EKK jtl: Current Oncology issn: 11980052 maglogo: N pubinfo: dt: May2026 vid: 33 iid: 5 pid: 97109 pub: MDPI artinfo: ui: 194129130 10.3390/curroncol33050258 194129130 ppf: 258 ppct: 10 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Overcoming Acquired MET-Driven Resistance to First-Line Lorlatinib: Successful Combination of Lorlatinib and Envafolimab in an ALK-Positive NSCLC Patient with Ultra-High PD-L1 Expression. aug: au: Ding, Lu Nuersulitan, Reyizha Wang, Jingjing Chen, Hanxiao Zhuo, Minglei affil: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department I of Thoracic Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China sug: ab: Simple Summary: Targeted therapy has significantly improved outcomes for patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC); however, the emergence of resistance remains an inevitable clinical challenge. Standard treatment after progression on third-generation ALK tyrosine kinase inhibitors (TKIs) is often restricted to chemotherapy, which may not be suitable or acceptable for all patients. We describe a patient with ALK-positive NSCLC and ultra-high PD-L1 expression whose disease progressed after first-line lorlatinib treatment. A repeat biopsy identified acquired MET amplification as a potential resistance mechanism. Given the limited standard options, the patient received a personalized combination of continued lorlatinib, envafolimab (an anti-PD-L1 antibody), and localized radiotherapy. This regimen induced a significant radiological response with a manageable safety profile. This case demonstrates that, in highly selected patients, a multi-modality strategy guided by repeat biopsy and biomarker profiling may provide meaningful clinical benefit after resistance to targeted therapies. Anaplastic lymphoma kinase (ALK) rearrangement is a well-established oncogenic driver alteration in non-small cell lung cancer (NSCLC), and ALK tyrosine kinase inhibitors (TKIs), particularly lorlatinib, have significantly improved the prognosis of ALK-positive NSCLC patients. Although high programmed death-ligand 1 (PD-L1) expression (≥50%) is generally associated with favorable responses to immune checkpoint inhibitors (ICIs), PD-L1 has not been shown to reliably predict ICI benefit in ALK-rearranged disease, and optimal management after ALK TKI resistance remains challenging. Herein, we report a case of an elderly patient with ALK-rearrangement and exceptionally high PD-L1 expression (TPS ≥ 95%) NSCLC who experienced disease progression following first-line lorlatinib with genetically confirmed MET amplification. The patient subsequently received an exploratory combination of continued lorlatinib plus envafolimab and achieved partial response (PR) with manageable tolerability after 4 months, highlighting a potential sequential strategy that may warrant further investigation in select ALK-positive NSCLC patients exhibiting both bypass pathway activation and exceptionally high PD-L1 expression. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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