Real-World Outcomes of Immunotherapy in Second- or Later-Line Non-Small Cell Lung Cancer with Actionable Genetic Alterations
Introduction: While the efficacy of immune checkpoint inhibitors (ICIs) in treating non-small cell lung cancer (NSCLC) patients with actionable genetic alterations (AGAs) is modest, certain patients demonstrate improved survival. Thus, this study aimed to evaluate the benefits of ICIs in NSCLC patie...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/22/5450 |
| _version_ | 1797459838146445312 |
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| author | Soojin Jun Sehhoon Park Jong-Mu Sun Se-Hoon Lee Jin Seok Ahn Myung-Ju Ahn Juhee Cho Hyun Ae Jung |
| author_facet | Soojin Jun Sehhoon Park Jong-Mu Sun Se-Hoon Lee Jin Seok Ahn Myung-Ju Ahn Juhee Cho Hyun Ae Jung |
| author_sort | Soojin Jun |
| collection | DOAJ |
| description | Introduction: While the efficacy of immune checkpoint inhibitors (ICIs) in treating non-small cell lung cancer (NSCLC) patients with actionable genetic alterations (AGAs) is modest, certain patients demonstrate improved survival. Thus, this study aimed to evaluate the benefits of ICIs in NSCLC patients with diverse AGAs and verify the predictive biomarkers of ICI efficacy. Methods: From January 2018 to July 2022, this study compared the progression-free survival (PFS) of NSCLC patients with different AGAs treated with ICI monotherapy as second- or later-line therapy at Samsung Medical Center. To ascertain the predictors of ICIs efficacy, we adjusted ICIs’ effects on PFS in terms of clinical and molecular biomarkers. Results: <i>EGFR</i> (46.0%) was the most prevalent mutation in 324 patients. In multivariate analysis, PD-L1 positivity (tumor proportion score (TPS) ≥ 1%) (HR = 0.41) and the use of steroids for immune-related adverse events (HR = 0.46) were positive factors for ICI therapy in the AGAs group. Co-existing mutation of <i>STK11</i> with <i>KRAS</i> mutation (HR = 4.53) and <i>TP53</i> with <i>MET</i> mutation (HR = 9.78) was negatively associated with survival. Conclusions: The efficacy of ICI treatment varied across AGA subtypes, but patients with <i>KRAS</i>, <i>MET</i>, and <i>BRAF</i> mutations demonstrated relatively long-duration benefits of ICI therapy. PD-L1 was a significant positive predictive biomarker in all AGA groups. |
| first_indexed | 2024-03-09T16:56:38Z |
| format | Article |
| id | doaj.art-5bcae98201094e6298bb40c4520131fd |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T16:56:38Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-5bcae98201094e6298bb40c4520131fd2023-11-24T14:34:33ZengMDPI AGCancers2072-66942023-11-011522545010.3390/cancers15225450Real-World Outcomes of Immunotherapy in Second- or Later-Line Non-Small Cell Lung Cancer with Actionable Genetic AlterationsSoojin Jun0Sehhoon Park1Jong-Mu Sun2Se-Hoon Lee3Jin Seok Ahn4Myung-Ju Ahn5Juhee Cho6Hyun Ae Jung7Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, Seoul 06355, Republic of KoreaDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of KoreaDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of KoreaDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of KoreaDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of KoreaDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of KoreaDepartment of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, Seoul 06355, Republic of KoreaDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of KoreaIntroduction: While the efficacy of immune checkpoint inhibitors (ICIs) in treating non-small cell lung cancer (NSCLC) patients with actionable genetic alterations (AGAs) is modest, certain patients demonstrate improved survival. Thus, this study aimed to evaluate the benefits of ICIs in NSCLC patients with diverse AGAs and verify the predictive biomarkers of ICI efficacy. Methods: From January 2018 to July 2022, this study compared the progression-free survival (PFS) of NSCLC patients with different AGAs treated with ICI monotherapy as second- or later-line therapy at Samsung Medical Center. To ascertain the predictors of ICIs efficacy, we adjusted ICIs’ effects on PFS in terms of clinical and molecular biomarkers. Results: <i>EGFR</i> (46.0%) was the most prevalent mutation in 324 patients. In multivariate analysis, PD-L1 positivity (tumor proportion score (TPS) ≥ 1%) (HR = 0.41) and the use of steroids for immune-related adverse events (HR = 0.46) were positive factors for ICI therapy in the AGAs group. Co-existing mutation of <i>STK11</i> with <i>KRAS</i> mutation (HR = 4.53) and <i>TP53</i> with <i>MET</i> mutation (HR = 9.78) was negatively associated with survival. Conclusions: The efficacy of ICI treatment varied across AGA subtypes, but patients with <i>KRAS</i>, <i>MET</i>, and <i>BRAF</i> mutations demonstrated relatively long-duration benefits of ICI therapy. PD-L1 was a significant positive predictive biomarker in all AGA groups.https://www.mdpi.com/2072-6694/15/22/5450non-small cell lung cancerimmune checkpoint inhibitorsactionable genetic alterationspredictive biomarkers |
| spellingShingle | Soojin Jun Sehhoon Park Jong-Mu Sun Se-Hoon Lee Jin Seok Ahn Myung-Ju Ahn Juhee Cho Hyun Ae Jung Real-World Outcomes of Immunotherapy in Second- or Later-Line Non-Small Cell Lung Cancer with Actionable Genetic Alterations Cancers non-small cell lung cancer immune checkpoint inhibitors actionable genetic alterations predictive biomarkers |
| title | Real-World Outcomes of Immunotherapy in Second- or Later-Line Non-Small Cell Lung Cancer with Actionable Genetic Alterations |
| title_full | Real-World Outcomes of Immunotherapy in Second- or Later-Line Non-Small Cell Lung Cancer with Actionable Genetic Alterations |
| title_fullStr | Real-World Outcomes of Immunotherapy in Second- or Later-Line Non-Small Cell Lung Cancer with Actionable Genetic Alterations |
| title_full_unstemmed | Real-World Outcomes of Immunotherapy in Second- or Later-Line Non-Small Cell Lung Cancer with Actionable Genetic Alterations |
| title_short | Real-World Outcomes of Immunotherapy in Second- or Later-Line Non-Small Cell Lung Cancer with Actionable Genetic Alterations |
| title_sort | real world outcomes of immunotherapy in second or later line non small cell lung cancer with actionable genetic alterations |
| topic | non-small cell lung cancer immune checkpoint inhibitors actionable genetic alterations predictive biomarkers |
| url | https://www.mdpi.com/2072-6694/15/22/5450 |
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