Neoadjuvant-Adjuvant vs Neoadjuvant-Only PD-1 and PD-L1 Inhibitors for Patients With Resectable NSCLC : An Indirect Meta-Analysis
Importance: Neoadjuvant therapy combining programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors with platinum-based chemotherapy has demonstrated significant improvement in pathologic response and survival rates among patients with resectable non-small cell lung cancer (NSCLC). However, it remains controversial whether PD-1 blockade therapy given before and after surgery (neoadjuvant-adjuvant treatment) is associated with better outcomes than when given only before surgery (neoadjuvant-only treatment).
Objective: To compare the efficacy and safety associated with neoadjuvant-adjuvant anti-PD-1 and anti-PD-L1 therapy with neoadjuvant-only anti-PD-1 and anti-PD-L1 therapy for patients with resectable NSCLC.
Data Sources: A systematic search was conducted across databases including PubMed, Embase, and the Cochrane Library, as well as major oncology conferences, through July 31, 2023.
Study Selection: Randomized clinical trials comparing neoadjuvant-adjuvant or neoadjuvant-only PD-1 and PD-L1 inhibitor therapy vs chemotherapy alone for patients with resectable NSCLC were selected.
Data Extraction and Synthesis: Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline, 2 authors independently extracted data. Hazard ratios (HRs) and 95% CIs for event-free survival (EFS) and overall survival (OS) were extracted and then pooled through the generic inverse-variance methods. Relative risks (RRs) for treatment-related adverse events (TRAEs) were derived via the Mantel-Haenszel method. Using chemotherapy as a common comparator, indirect comparisons between neoadjuvant-adjuvant immunotherapy and neoadjuvant-only immunotherapy were conducted using frequentist methods. A random or fixed model was used based on intertrial heterogeneity identified through the Cochran Q test.
Main Outcomes and Measures: The primary outcome was EFS, with secondary outcomes including OS and TRAEs.
Results: The study encompassed 4 trials of neoadjuvant-adjuvant immunotherapy and 1 trial of neoadjuvant-only immunotherapy, involving 2385 patients. Direct meta-analysis revealed significant improvements in EFS for both neoadjuvant-adjuvant and neoadjuvant-only immunotherapy compared with chemotherapy alone. In indirect meta-analysis, the addition of adjuvant immunotherapy to neoadjuvant immunotherapy was not associated with improved EFS (HR, 0.90; 95% CI, 0.63-1.30; P = .59) or OS (HR, 1.18; 95% CI, 0.73-1.90; P = .51) compared with neoadjuvant-only immunotherapy. Moreover, the incidence of any grade of TRAEs significantly increased with the addition of adjuvant immunotherapy (RR, 1.08; 95% CI, 1.00-1.17; P = .04).
Conclusions and Relevance: This meta-analysis suggests that adding PD-1 or PD-L1 inhibitors in the adjuvant phase to neoadjuvant treatment with PD-1 or PD-L1 inhibitors and chemotherapy may not improve survival outcomes for patients with resectable NSCLC and may be associated with increased adverse events. Future validation of these findings is warranted through head-to-head randomized clinical trials.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:7 |
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| Enthalten in: |
JAMA network open - 7(2024), 3 vom: 04. März, Seite e241285 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhou, Yixin [VerfasserIn] |
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| Links: |
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| Themen: |
Adjuvants, Immunologic |
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| Anmerkungen: |
Date Completed 08.03.2024 Date Revised 10.03.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1001/jamanetworkopen.2024.1285 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369412842 |
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| 245 | 1 | 0 | |a Neoadjuvant-Adjuvant vs Neoadjuvant-Only PD-1 and PD-L1 Inhibitors for Patients With Resectable NSCLC |b An Indirect Meta-Analysis |
| 264 | 1 | |c 2024 | |
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| 500 | |a Date Completed 08.03.2024 | ||
| 500 | |a Date Revised 10.03.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Importance: Neoadjuvant therapy combining programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors with platinum-based chemotherapy has demonstrated significant improvement in pathologic response and survival rates among patients with resectable non-small cell lung cancer (NSCLC). However, it remains controversial whether PD-1 blockade therapy given before and after surgery (neoadjuvant-adjuvant treatment) is associated with better outcomes than when given only before surgery (neoadjuvant-only treatment) | ||
| 520 | |a Objective: To compare the efficacy and safety associated with neoadjuvant-adjuvant anti-PD-1 and anti-PD-L1 therapy with neoadjuvant-only anti-PD-1 and anti-PD-L1 therapy for patients with resectable NSCLC | ||
| 520 | |a Data Sources: A systematic search was conducted across databases including PubMed, Embase, and the Cochrane Library, as well as major oncology conferences, through July 31, 2023 | ||
| 520 | |a Study Selection: Randomized clinical trials comparing neoadjuvant-adjuvant or neoadjuvant-only PD-1 and PD-L1 inhibitor therapy vs chemotherapy alone for patients with resectable NSCLC were selected | ||
| 520 | |a Data Extraction and Synthesis: Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline, 2 authors independently extracted data. Hazard ratios (HRs) and 95% CIs for event-free survival (EFS) and overall survival (OS) were extracted and then pooled through the generic inverse-variance methods. Relative risks (RRs) for treatment-related adverse events (TRAEs) were derived via the Mantel-Haenszel method. Using chemotherapy as a common comparator, indirect comparisons between neoadjuvant-adjuvant immunotherapy and neoadjuvant-only immunotherapy were conducted using frequentist methods. A random or fixed model was used based on intertrial heterogeneity identified through the Cochran Q test | ||
| 520 | |a Main Outcomes and Measures: The primary outcome was EFS, with secondary outcomes including OS and TRAEs | ||
| 520 | |a Results: The study encompassed 4 trials of neoadjuvant-adjuvant immunotherapy and 1 trial of neoadjuvant-only immunotherapy, involving 2385 patients. Direct meta-analysis revealed significant improvements in EFS for both neoadjuvant-adjuvant and neoadjuvant-only immunotherapy compared with chemotherapy alone. In indirect meta-analysis, the addition of adjuvant immunotherapy to neoadjuvant immunotherapy was not associated with improved EFS (HR, 0.90; 95% CI, 0.63-1.30; P = .59) or OS (HR, 1.18; 95% CI, 0.73-1.90; P = .51) compared with neoadjuvant-only immunotherapy. Moreover, the incidence of any grade of TRAEs significantly increased with the addition of adjuvant immunotherapy (RR, 1.08; 95% CI, 1.00-1.17; P = .04) | ||
| 520 | |a Conclusions and Relevance: This meta-analysis suggests that adding PD-1 or PD-L1 inhibitors in the adjuvant phase to neoadjuvant treatment with PD-1 or PD-L1 inhibitors and chemotherapy may not improve survival outcomes for patients with resectable NSCLC and may be associated with increased adverse events. Future validation of these findings is warranted through head-to-head randomized clinical trials | ||
| 650 | 4 | |a Meta-Analysis | |
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Immune Checkpoint Inhibitors |2 NLM | |
| 650 | 7 | |a Programmed Cell Death 1 Receptor |2 NLM | |
| 650 | 7 | |a Adjuvants, Immunologic |2 NLM | |
| 700 | 1 | |a Li, Anlin |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yuhong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xuanye |e verfasserin |4 aut | |
| 700 | 1 | |a Qiu, Huijuan |e verfasserin |4 aut | |
| 700 | 1 | |a Du, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Linfeng |e verfasserin |4 aut | |
| 700 | 1 | |a Fu, Sha |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Li |e verfasserin |4 aut | |
| 700 | 1 | |a Hong, Shaodong |e verfasserin |4 aut | |
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