BRAF Mutant Lung Cancer : Programmed Death Ligand 1 Expression, Tumor Mutational Burden, Microsatellite Instability Status, and Response to Immune Check-Point Inhibitors
Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved..
INTRODUCTION: The efficacy of immune checkpoint inhibitors (ICPi) in BRAF mutant NSCLC is unknown.
METHODS: Multi-institutional retrospective chart review identified 39 patients with BRAF mutant NSCLC. The patients were divided into two groups: V600E (group A, n = 21) and non-V600E (group B, n = 18). Programmed death ligand 1 (PD-L1) expression, tumor mutational burden (TMB) and microsatellite instability status were assessed in 29 (74%), 11 (28%), and 12 (31%) patients, respectively. Objective response rate, progression-free survival (PFS) with ICPi, and overall survival were analyzed.
RESULTS: High (≥50%), intermediate (1-49%), and no (<1%) PD-L1 expression was observed in 8 of 19 (42%), 6 of 19 (32%), 5 of 19 (26%), and 5 of 10 (50%), 1 of 10 (10%), and 4 of 10 (40%) cases in groups A and B, respectively. Two tumors in group A showed high TMB (25%); none were microsatellite instability status-high. Twenty-two patients (group A, n = 12; group B, n = 10) received ICPi. Objective response rate with ICPi was 25% and 33% in groups A and B, respectively (p = 1.0). Median PFS with ICPi was 3.7 months (95% confidence interval [CI]: 1.6-6.6), and 4.1 months (95% CI: 0.1-19.6) in groups A and B, respectively (log-rank test = 0.81, p = 0.37). Neither BRAF mutation type nor PD-L1 expression affected the response probability/PFS. Median overall survival was not reached (95% CI: 13-NR) and comprised 21.1 months (95% CI: 1.8-NR) for patients who were and were not exposed to ICPi, respectively (log-rank test = 5.58, p = 0.018).
CONCLUSIONS: BRAF mutant NSCLC is associated with high level of PD-L1 expression, low/intermediate TMB and microsatellite-stable status. ICPi have favorable activity both in BRAF V600E and BRAF non-V600E mutant NSCLC.
| Errataetall: |
CommentIn: J Thorac Oncol. 2018 Aug;13(8):1055-1057. - PMID 30056857 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer - 13(2018), 8 vom: 20. Aug., Seite 1128-1137 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Dudnik, Elizabeth [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 30.09.2019 Date Revised 09.04.2022 published: Print-Electronic CommentIn: J Thorac Oncol. 2018 Aug;13(8):1055-1057. - PMID 30056857 Citation Status MEDLINE |
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| doi: |
10.1016/j.jtho.2018.04.024 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM283708468 |
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| 100 | 1 | |a Dudnik, Elizabeth |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a BRAF Mutant Lung Cancer |b Programmed Death Ligand 1 Expression, Tumor Mutational Burden, Microsatellite Instability Status, and Response to Immune Check-Point Inhibitors |
| 264 | 1 | |c 2018 | |
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| 500 | |a Date Completed 30.09.2019 | ||
| 500 | |a Date Revised 09.04.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a CommentIn: J Thorac Oncol. 2018 Aug;13(8):1055-1057. - PMID 30056857 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a INTRODUCTION: The efficacy of immune checkpoint inhibitors (ICPi) in BRAF mutant NSCLC is unknown | ||
| 520 | |a METHODS: Multi-institutional retrospective chart review identified 39 patients with BRAF mutant NSCLC. The patients were divided into two groups: V600E (group A, n = 21) and non-V600E (group B, n = 18). Programmed death ligand 1 (PD-L1) expression, tumor mutational burden (TMB) and microsatellite instability status were assessed in 29 (74%), 11 (28%), and 12 (31%) patients, respectively. Objective response rate, progression-free survival (PFS) with ICPi, and overall survival were analyzed | ||
| 520 | |a RESULTS: High (≥50%), intermediate (1-49%), and no (<1%) PD-L1 expression was observed in 8 of 19 (42%), 6 of 19 (32%), 5 of 19 (26%), and 5 of 10 (50%), 1 of 10 (10%), and 4 of 10 (40%) cases in groups A and B, respectively. Two tumors in group A showed high TMB (25%); none were microsatellite instability status-high. Twenty-two patients (group A, n = 12; group B, n = 10) received ICPi. Objective response rate with ICPi was 25% and 33% in groups A and B, respectively (p = 1.0). Median PFS with ICPi was 3.7 months (95% confidence interval [CI]: 1.6-6.6), and 4.1 months (95% CI: 0.1-19.6) in groups A and B, respectively (log-rank test = 0.81, p = 0.37). Neither BRAF mutation type nor PD-L1 expression affected the response probability/PFS. Median overall survival was not reached (95% CI: 13-NR) and comprised 21.1 months (95% CI: 1.8-NR) for patients who were and were not exposed to ICPi, respectively (log-rank test = 5.58, p = 0.018) | ||
| 520 | |a CONCLUSIONS: BRAF mutant NSCLC is associated with high level of PD-L1 expression, low/intermediate TMB and microsatellite-stable status. ICPi have favorable activity both in BRAF V600E and BRAF non-V600E mutant NSCLC | ||
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