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http://ir.nhri.org.tw/handle/3990099045/16460
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| Title: | Atezolizumab, bevacizumab, pemetrexed and platinum for EGFR-mutant NSCLC patients after EGFR TKI failure: A phase II study with immune cell profile analysis |
| Authors: | Wu, SG;Ho, CC;Yang, JC;Yu, SH;Lin, YF;Lin, SC;Liao, BC;Yang, CY;Lin, YT;Yu, CJ;Chuang, YT;Liao, WY;Yap, KY;Kou, WS;Shih, JY |
| Contributors: | Center for Neuropsychiatric Research |
| Abstract: | BACKGROUND: Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) remains a significant hurdle for patients with EGFR-mutated non-small cell lung cancer (NSCLC), particularly those lacking the EGFR(T790M). IMpower 150 study demonstrated promising efficacy for a combination of immune-chemotherapy and bevacizumab in patients with EGFR-mutated NSCLC. METHODS: This open-label, single-arm, phase II trial evaluated the efficacy and immune cell profile of the modified regimen combining atezolizumab, bevacizumab (7.5 mg/kg) and chemotherapy in patients with EGFR-mutated NSCLC following TKI failure. The primary endpoint was objective response rate (ORR). The re-biopsy tissue specimens and serial peripheral blood samples were collected to analyse the immune cell profile and tumour microenvironments. RRESULTS: 22 EGFR-mutant NSCLC patients participated in this study. The ORR was 42.9%, with a disease control rate (DCR) of 100%. Median progression-free survival (PFS) was 6.3 months. Patients with programmed death-ligand 1 (PD-L1) expression ≥1% exhibited significantly higher ORR (75 vs. 23.1%; p = .032) and longer PFS (14.0 vs. 6.1 months; p = .022) compared with those with PD-L1 expression < 1%. Grade ≥ 3 adverse events occurred in 40.9% of patients. Higher peritumour nature killer (NK) cell infiltration and lower peripheral helper T cell counts before treatment were associated with favourable ORR and longer PFS, respectively. After disease progression, the proportion of S100A9(+) myelod-derived suppressor cells (MDSCs) increased, while regulatory T cells decreased. CONCLUSION: This modified combination regimen may be a promising therapeutic option for EGFR-mutant NSCLC patients with TKI resistance, especially those with PD-L1-positive tumours. Furthermore, immune cell profiling may aid in identifying patients who may benefit from this approach. KEY POINTS: The combination regimen yielded promising efficacy in NSCLC patients after EGFR-TKI resistance, particularly those with PD-L1-positive tumours. Higher peritumour NK cell and lower peripheral helper T cell were associated with favourable ORR and longer PFS, respectively. After disease progression, the proportion of S100A9(+) MDSC increased, but Treg cells decreased. |
| Date: | 2025-01 |
| Relation: | Clinical and Translational Medicine. 2025 Jan;15(1):Article number e70149. |
| Link to: | http://dx.doi.org/10.1002/ctm2.70149 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:001382699200001 |
| Appears in Collections: | [林彥鋒] 期刊論文
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| PUB39715697.pdf | | 2774Kb | Adobe PDF | 40 | View/Open |
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