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Neoadjuvant PD-1 Blockade in Resectable Lung Cancer.
- Source :
-
The New England journal of medicine [N Engl J Med] 2018 May 24; Vol. 378 (21), pp. 1976-1986. Date of Electronic Publication: 2018 Apr 16. - Publication Year :
- 2018
-
Abstract
- Background: Antibodies that block programmed death 1 (PD-1) protein improve survival in patients with advanced non-small-cell lung cancer (NSCLC) but have not been tested in resectable NSCLC, a condition in which little progress has been made during the past decade.<br />Methods: In this pilot study, we administered two preoperative doses of PD-1 inhibitor nivolumab in adults with untreated, surgically resectable early (stage I, II, or IIIA) NSCLC. Nivolumab (at a dose of 3 mg per kilogram of body weight) was administered intravenously every 2 weeks, with surgery planned approximately 4 weeks after the first dose. The primary end points of the study were safety and feasibility. We also evaluated the tumor pathological response, expression of programmed death ligand 1 (PD-L1), mutational burden, and mutation-associated, neoantigen-specific T-cell responses.<br />Results: Neoadjuvant nivolumab had an acceptable side-effect profile and was not associated with delays in surgery. Of the 21 tumors that were removed, 20 were completely resected. A major pathological response occurred in 9 of 20 resected tumors (45%). Responses occurred in both PD-L1-positive and PD-L1-negative tumors. There was a significant correlation between the pathological response and the pretreatment tumor mutational burden. The number of T-cell clones that were found in both the tumor and peripheral blood increased systemically after PD-1 blockade in eight of nine patients who were evaluated. Mutation-associated, neoantigen-specific T-cell clones from a primary tumor with a complete response on pathological assessment rapidly expanded in peripheral blood at 2 to 4 weeks after treatment; some of these clones were not detected before the administration of nivolumab.<br />Conclusions: Neoadjuvant nivolumab was associated with few side effects, did not delay surgery, and induced a major pathological response in 45% of resected tumors. The tumor mutational burden was predictive of the pathological response to PD-1 blockade. Treatment induced expansion of mutation-associated, neoantigen-specific T-cell clones in peripheral blood. (Funded by Cancer Research Institute-Stand Up 2 Cancer and others; ClinicalTrials.gov number, NCT02259621 .).
- Subjects :
- Adenocarcinoma pathology
Aged
Aged, 80 and over
Antibodies, Monoclonal adverse effects
Antineoplastic Agents adverse effects
Biopsy
Carcinoma, Non-Small-Cell Lung genetics
Carcinoma, Non-Small-Cell Lung pathology
Carcinoma, Non-Small-Cell Lung surgery
Carcinoma, Squamous Cell pathology
Female
Humans
Lung Neoplasms genetics
Lung Neoplasms pathology
Lung Neoplasms surgery
Male
Middle Aged
Mutation
Neoadjuvant Therapy
Nivolumab
Pilot Projects
Antibodies, Monoclonal therapeutic use
Antineoplastic Agents therapeutic use
B7-H1 Antigen antagonists & inhibitors
Carcinoma, Non-Small-Cell Lung drug therapy
Lung Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1533-4406
- Volume :
- 378
- Issue :
- 21
- Database :
- MEDLINE
- Journal :
- The New England journal of medicine
- Publication Type :
- Academic Journal
- Accession number :
- 29658848
- Full Text :
- https://doi.org/10.1056/NEJMoa1716078