Immunotherapy-based regimens for patients with EGFR-mutated non-small cell lung cancer who progressed on EGFR-TKI therapy

The sustained benefit of immunotherapy-based regimens in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) after EGFR-tyrosine kinase inhibitor (TKI) failure is debatable. Neither Checkmate-722 nor Keynote-789 reached the prespecified statistical level of clinical be...

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Main Authors: Ying Wu, Yan Ling, Bao-Dong Qin, Xiao-Dong Jiao, Ling-Yan Yuan, Yuan-Sheng Zang
Format: Article
Language:English
Published: BMJ Publishing Group 2024-04-01
Series:Journal for ImmunoTherapy of Cancer
Online Access:https://jitc.bmj.com/content/12/4/e008818.full
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author Ying Wu
Yan Ling
Bao-Dong Qin
Xiao-Dong Jiao
Ling-Yan Yuan
Yuan-Sheng Zang
author_facet Ying Wu
Yan Ling
Bao-Dong Qin
Xiao-Dong Jiao
Ling-Yan Yuan
Yuan-Sheng Zang
author_sort Ying Wu
collection DOAJ
description The sustained benefit of immunotherapy-based regimens in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) after EGFR-tyrosine kinase inhibitor (TKI) failure is debatable. Neither Checkmate-722 nor Keynote-789 reached the prespecified statistical level of clinical benefit, but the ORIENT-31 and ATTLAS trials showed that the addition of a VEGF inhibitor to immunotherapy plus chemotherapy could significantly prolong survival. However, head-to-head comparisons of the efficacy of immunotherapy plus bevacizumab with chemotherapy versus that of immunotherapy with chemotherapy in this patient population are lacking. In addition, the critical question of who would benefit from an immunotherapy-based regimen remains unclear. We conducted an indirect comparative meta-analysis using chemotherapy as a common comparator to classify the relative efficacy of the two immunotherapy-based regimens. The indirect comparison showed that immunotherapy and bevacizumab plus chemotherapy had a significantly better progression-free survival (PFS) (HRIO+Bev+Chemo/IO+Chemo=0.71, 95% CI 0.55 to 0.91) than immunotherapy plus chemotherapy. The EGFR mutation type and T790M mutation were found to be significantly associated with PFS of immunotherapy-based regimens. Compared with their counterparts, patients with L858R (HR 0.52, 95%CI 0.37 to 0.72), without T790M mutation (HR 0.50, 95% CI 0.35 to 0.71) tended to benefit significantly more from immunotherapy-based regimens. In conclusion, our findings support that the addition of VEGF inhibitor to immunotherapy and chemotherapy could be the preferred option for TKI-resistant, EGFR-mutated NSCLC, and that L858R mutation and T790M negativity could be identified as efficacy-associated factors for immunotherapy-based regimens.
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series Journal for ImmunoTherapy of Cancer
spelling doaj-art-01fa2f4d72644d12bacdd7c6eb71c1e02024-11-14T03:10:08ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262024-04-0112410.1136/jitc-2024-008818Immunotherapy-based regimens for patients with EGFR-mutated non-small cell lung cancer who progressed on EGFR-TKI therapyYing Wu0Yan Ling1Bao-Dong Qin2Xiao-Dong Jiao3Ling-Yan Yuan4Yuan-Sheng Zang56 School of Statistics and Data Science, Nankai University, Key Laboratory for Medical Data Analysis and Statistical Research of Tianjin, Tianjin, ChinaDepartment of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, People`s Republic of ChinaDepartment of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, People`s Republic of ChinaDepartment of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, People`s Republic of ChinaDepartment of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, People`s Republic of ChinaDepartment of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, People`s Republic of ChinaThe sustained benefit of immunotherapy-based regimens in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) after EGFR-tyrosine kinase inhibitor (TKI) failure is debatable. Neither Checkmate-722 nor Keynote-789 reached the prespecified statistical level of clinical benefit, but the ORIENT-31 and ATTLAS trials showed that the addition of a VEGF inhibitor to immunotherapy plus chemotherapy could significantly prolong survival. However, head-to-head comparisons of the efficacy of immunotherapy plus bevacizumab with chemotherapy versus that of immunotherapy with chemotherapy in this patient population are lacking. In addition, the critical question of who would benefit from an immunotherapy-based regimen remains unclear. We conducted an indirect comparative meta-analysis using chemotherapy as a common comparator to classify the relative efficacy of the two immunotherapy-based regimens. The indirect comparison showed that immunotherapy and bevacizumab plus chemotherapy had a significantly better progression-free survival (PFS) (HRIO+Bev+Chemo/IO+Chemo=0.71, 95% CI 0.55 to 0.91) than immunotherapy plus chemotherapy. The EGFR mutation type and T790M mutation were found to be significantly associated with PFS of immunotherapy-based regimens. Compared with their counterparts, patients with L858R (HR 0.52, 95%CI 0.37 to 0.72), without T790M mutation (HR 0.50, 95% CI 0.35 to 0.71) tended to benefit significantly more from immunotherapy-based regimens. In conclusion, our findings support that the addition of VEGF inhibitor to immunotherapy and chemotherapy could be the preferred option for TKI-resistant, EGFR-mutated NSCLC, and that L858R mutation and T790M negativity could be identified as efficacy-associated factors for immunotherapy-based regimens.https://jitc.bmj.com/content/12/4/e008818.full
spellingShingle Ying Wu
Yan Ling
Bao-Dong Qin
Xiao-Dong Jiao
Ling-Yan Yuan
Yuan-Sheng Zang
Immunotherapy-based regimens for patients with EGFR-mutated non-small cell lung cancer who progressed on EGFR-TKI therapy
Journal for ImmunoTherapy of Cancer
title Immunotherapy-based regimens for patients with EGFR-mutated non-small cell lung cancer who progressed on EGFR-TKI therapy
title_full Immunotherapy-based regimens for patients with EGFR-mutated non-small cell lung cancer who progressed on EGFR-TKI therapy
title_fullStr Immunotherapy-based regimens for patients with EGFR-mutated non-small cell lung cancer who progressed on EGFR-TKI therapy
title_full_unstemmed Immunotherapy-based regimens for patients with EGFR-mutated non-small cell lung cancer who progressed on EGFR-TKI therapy
title_short Immunotherapy-based regimens for patients with EGFR-mutated non-small cell lung cancer who progressed on EGFR-TKI therapy
title_sort immunotherapy based regimens for patients with egfr mutated non small cell lung cancer who progressed on egfr tki therapy
url https://jitc.bmj.com/content/12/4/e008818.full
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