Atezolizumab, bevacizumab, pemetrexed and platinum for EGFR‐mutant NSCLC patients after EGFR TKI failure: A phase II study with immune cell profile analysis
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 EGFRT790M. IMpower 150 study demonstrated promising effica...
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2025-01-01
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| Online Access: | https://doi.org/10.1002/ctm2.70149 |
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| author | Shang‐Gin Wu Chao‐Chi Ho James Chih‐Hsin Yang Shu‐Han Yu Yen‐Feng Lin Shu‐Chin Lin Bin‐Chi Liao Ching‐Yao Yang Yen‐Ting Lin Chong‐Jen Yu Ya‐Ting Chuang Wei‐Yu Liao Kah Yi Yap Weng Si Kou Jin‐Yuan Shih |
| author_facet | Shang‐Gin Wu Chao‐Chi Ho James Chih‐Hsin Yang Shu‐Han Yu Yen‐Feng Lin Shu‐Chin Lin Bin‐Chi Liao Ching‐Yao Yang Yen‐Ting Lin Chong‐Jen Yu Ya‐Ting Chuang Wei‐Yu Liao Kah Yi Yap Weng Si Kou Jin‐Yuan Shih |
| author_sort | Shang‐Gin Wu |
| collection | DOAJ |
| description | 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 EGFRT790M. 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. |
| format | Article |
| id | doaj-art-6baafecd35de4b68b2b1383f366ecc9b |
| institution | Kabale University |
| issn | 2001-1326 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
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| series | Clinical and Translational Medicine |
| spelling | doaj-art-6baafecd35de4b68b2b1383f366ecc9b2025-01-25T04:00:38ZengWileyClinical and Translational Medicine2001-13262025-01-01151n/an/a10.1002/ctm2.70149Atezolizumab, bevacizumab, pemetrexed and platinum for EGFR‐mutant NSCLC patients after EGFR TKI failure: A phase II study with immune cell profile analysisShang‐Gin Wu0Chao‐Chi Ho1James Chih‐Hsin Yang2Shu‐Han Yu3Yen‐Feng Lin4Shu‐Chin Lin5Bin‐Chi Liao6Ching‐Yao Yang7Yen‐Ting Lin8Chong‐Jen Yu9Ya‐Ting Chuang10Wei‐Yu Liao11Kah Yi Yap12Weng Si Kou13Jin‐Yuan Shih14Department of Internal Medicine National Taiwan University Cancer Center Taipei TaiwanDepartment of Internal Medicine National Taiwan University Hospital Taipei TaiwanDepartment of Oncology National Taiwan University Cancer Center Taipei TaiwanInstitute of Biotechnology National Taiwan University Taipei TaiwanCenter for Neuropsychiatric Research National Health Research Institutes Miaoli TaiwanCenter for Neuropsychiatric Research National Health Research Institutes Miaoli TaiwanDepartment of Oncology National Taiwan University Cancer Center Taipei TaiwanDepartment of Internal Medicine National Taiwan University Hospital Taipei TaiwanDepartment of Internal Medicine National Taiwan University Cancer Center Taipei TaiwanDepartment of Internal Medicine National Taiwan University Hospital Taipei TaiwanDepartment of Medical Research National Taiwan University Hospital Taipei TaiwanDepartment of Internal Medicine National Taiwan University Hospital Taipei TaiwanInstitute of Biotechnology National Taiwan University Taipei TaiwanInstitute of Biotechnology National Taiwan University Taipei TaiwanDepartment of Internal Medicine National Taiwan University Hospital Taipei TaiwanAbstract 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 EGFRT790M. 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.https://doi.org/10.1002/ctm2.70149anti‐angiogenesisatezolizumabEGFR TKI resistanceimmune celltumour microenvironment |
| spellingShingle | Shang‐Gin Wu Chao‐Chi Ho James Chih‐Hsin Yang Shu‐Han Yu Yen‐Feng Lin Shu‐Chin Lin Bin‐Chi Liao Ching‐Yao Yang Yen‐Ting Lin Chong‐Jen Yu Ya‐Ting Chuang Wei‐Yu Liao Kah Yi Yap Weng Si Kou Jin‐Yuan Shih Atezolizumab, bevacizumab, pemetrexed and platinum for EGFR‐mutant NSCLC patients after EGFR TKI failure: A phase II study with immune cell profile analysis Clinical and Translational Medicine anti‐angiogenesis atezolizumab EGFR TKI resistance immune cell tumour microenvironment |
| title | Atezolizumab, bevacizumab, pemetrexed and platinum for EGFR‐mutant NSCLC patients after EGFR TKI failure: A phase II study with immune cell profile analysis |
| title_full | Atezolizumab, bevacizumab, pemetrexed and platinum for EGFR‐mutant NSCLC patients after EGFR TKI failure: A phase II study with immune cell profile analysis |
| title_fullStr | Atezolizumab, bevacizumab, pemetrexed and platinum for EGFR‐mutant NSCLC patients after EGFR TKI failure: A phase II study with immune cell profile analysis |
| title_full_unstemmed | Atezolizumab, bevacizumab, pemetrexed and platinum for EGFR‐mutant NSCLC patients after EGFR TKI failure: A phase II study with immune cell profile analysis |
| title_short | Atezolizumab, bevacizumab, pemetrexed and platinum for EGFR‐mutant NSCLC patients after EGFR TKI failure: A phase II study with immune cell profile analysis |
| title_sort | atezolizumab bevacizumab pemetrexed and platinum for egfr mutant nsclc patients after egfr tki failure a phase ii study with immune cell profile analysis |
| topic | anti‐angiogenesis atezolizumab EGFR TKI resistance immune cell tumour microenvironment |
| url | https://doi.org/10.1002/ctm2.70149 |
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