Surgical Perspective on Neoadjuvant Immunotherapy in Non-Small Cell Lung Cancer.
Journal
The Annals of thoracic surgery
ISSN: 1552-6259
Titre abrégé: Ann Thorac Surg
Pays: Netherlands
ID NLM: 15030100R
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
received:
08
01
2021
revised:
25
05
2021
accepted:
22
06
2021
pubmed:
3
8
2021
medline:
30
9
2022
entrez:
2
8
2021
Statut:
ppublish
Résumé
With a 5% improvement in 5-year overall survival achieved with current neoadjuvant or adjuvant chemotherapy, new treatments for resectable non-small cell lung cancer (NSCLC) are urgently needed. The use of immune checkpoint inhibitors (ICIs) is established in metastatic NSCLC and is being evaluated in resectable NSCLC. Publications and conference databases and clinicaltrials.gov were searched for reports on clinical studies of neoadjuvant immunotherapy in patients with early resectable NSCLC. Potential advantages of neoadjuvant ICIs include the following: earlier treatment of micrometastatic disease; activation of a broader, potentially durable immune response by the whole tumor and associated lymph nodes; and pathologic assessment of neoadjuvant treatment response, which may guide adjuvant therapy. Surgical considerations include delays to surgery, potential disease progression preventing curative resection, and perioperative morbidity and mortality. Surrogate end points of efficacy (pathologic complete response, major pathologic response) and biomarkers predictive of outcome (programmed death ligand 1 expression, tumor mutational burden, and circulating tumor DNA) can accelerate clinical trial completion and early-stage treatment development; their application in neoadjuvant ICI studies in NSCLC is reviewed. Phase 2 trials of neoadjuvant ICIs alone or in combination with chemotherapy showed encouraging safety and efficacy in patients with resectable NSCLC, thus warranting the ongoing phase 3 studies of neoadjuvant immunotherapy combined with chemotherapy. Preoperative and intraoperative unresectability after neoadjuvant ICIs appears comparable to that observed with neoadjuvant chemotherapy. To help thoracic surgeons and medical oncologists to distinguish among ICIs beyond efficacy as phase 3 data emerge, surgery-related end points for perioperative morbidity, mortality, and complexity should be defined, standardized, incorporated into trial designs, and reported.
Sections du résumé
BACKGROUND
With a 5% improvement in 5-year overall survival achieved with current neoadjuvant or adjuvant chemotherapy, new treatments for resectable non-small cell lung cancer (NSCLC) are urgently needed. The use of immune checkpoint inhibitors (ICIs) is established in metastatic NSCLC and is being evaluated in resectable NSCLC.
METHODS
Publications and conference databases and clinicaltrials.gov were searched for reports on clinical studies of neoadjuvant immunotherapy in patients with early resectable NSCLC.
RESULTS
Potential advantages of neoadjuvant ICIs include the following: earlier treatment of micrometastatic disease; activation of a broader, potentially durable immune response by the whole tumor and associated lymph nodes; and pathologic assessment of neoadjuvant treatment response, which may guide adjuvant therapy. Surgical considerations include delays to surgery, potential disease progression preventing curative resection, and perioperative morbidity and mortality. Surrogate end points of efficacy (pathologic complete response, major pathologic response) and biomarkers predictive of outcome (programmed death ligand 1 expression, tumor mutational burden, and circulating tumor DNA) can accelerate clinical trial completion and early-stage treatment development; their application in neoadjuvant ICI studies in NSCLC is reviewed.
CONCLUSIONS
Phase 2 trials of neoadjuvant ICIs alone or in combination with chemotherapy showed encouraging safety and efficacy in patients with resectable NSCLC, thus warranting the ongoing phase 3 studies of neoadjuvant immunotherapy combined with chemotherapy. Preoperative and intraoperative unresectability after neoadjuvant ICIs appears comparable to that observed with neoadjuvant chemotherapy. To help thoracic surgeons and medical oncologists to distinguish among ICIs beyond efficacy as phase 3 data emerge, surgery-related end points for perioperative morbidity, mortality, and complexity should be defined, standardized, incorporated into trial designs, and reported.
Identifiants
pubmed: 34339672
pii: S0003-4975(21)01300-X
doi: 10.1016/j.athoracsur.2021.06.069
pii:
doi:
Substances chimiques
B7-H1 Antigen
0
Circulating Tumor DNA
0
Immune Checkpoint Inhibitors
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1505-1515Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.