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Clinical Trial
. 2019 Jul;158(1):269-276.
doi: 10.1016/j.jtcvs.2018.11.124. Epub 2018 Dec 13.

Initial results of pulmonary resection after neoadjuvant nivolumab in patients with resectable non-small cell lung cancer

Matthew J Bott  1 , Stephen C Yang  2 , Bernard J Park  1 , Prasad S Adusumilli  1 , Valerie W Rusch  1 , James M Isbell  1 , Robert J Downey  1 , Julie R Brahmer  3 , Richard Battafarano  2 , Errol Bush  2 , Jamie Chaft  4 , Patrick M Forde  3 , David R Jones  1 , Stephen R Broderick  5
Affiliations
Clinical Trial

Initial results of pulmonary resection after neoadjuvant nivolumab in patients with resectable non-small cell lung cancer

Matthew J Bott et al. J Thorac Cardiovasc Surg. 2019 Jul.

Abstract

Objective: We conducted a phase I trial of neoadjuvant nivolumab, a monoclonal antibody to the programmed cell death protein 1 checkpoint receptor, in patients with resectable non-small cell lung cancer. We analyzed perioperative outcomes to assess the safety of this strategy.

Methods: Patients with untreated stage I-IIIA non-small cell lung cancer underwent neoadjuvant therapy with 2 cycles of nivolumab (3 mg/kg), 4 and 2 weeks before resection. Patients underwent invasive mediastinal staging as indicated and post-treatment computed tomography. Primary study end points were safety and feasibility of neoadjuvant nivolumab followed by pulmonary resection. Data on additional surgical details were collected through chart review.

Results: Of 22 patients enrolled, 20 underwent resection. One was unresectable; another had small cell histologic subtype. There were no delays to surgical resection. Median time from first treatment to surgery was 33 (range, 17-43) days. There were 15 lobectomies, 2 pneumonectomies, 1 bilobectomy, 1 sleeve lobectomy, and 1 wedge resection. Of 13 procedures attempted via a video-assisted thoracoscopic surgery or robotic approach, 7 (54%) required thoracotomy. Median operative time was 228 (range, 132-312) minutes; estimated blood loss was 100 (range, 25-1000) mL; length of hospital stay was 4 (range, 2-17) days. There was no operative mortality. Morbidity occurred in 10 of 20 patients (50%). The most common postoperative complication was atrial arrhythmia (6/20; 30%). Major pathologic response was identified in 9 of 20 patients (45%).

Conclusions: Neoadjuvant therapy with nivolumab was not associated with unexpected perioperative morbidity or mortality. More than half of the video-assisted thoracoscopic surgery/robotic cases were converted to thoracotomy, often because of hilar inflammation and fibrosis.

Keywords: NSCLC; immune checkpoint inhibition; immunotherapy; neoadjuvant.

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Conflict of interest statement

All other authors declare no conflicts of interest.

Figures

Central Picture:
Central Picture:
Pre- (top) and post- (bottom) nivolumab. Imaging often underestimates pathologic response. Central Message: Pulmonary resection after neoadjuvant therapy with nivolumab did not result in undue morbidity or mortality. Major pathologic responses were identified despite stable disease radiographically.
See this image and copyright information in PMC

Comment in

  • Discussion.
    [No authors listed] [No authors listed] J Thorac Cardiovasc Surg. 2019 Jul;158(1):275-276. doi: 10.1016/j.jtcvs.2018.11.134. Epub 2019 Feb 1. J Thorac Cardiovasc Surg. 2019. PMID: 30718049 No abstract available.
  • Commentary: Cautious optimism for induction immunotherapy in resectable lung cancer.
    Lanuti M. Lanuti M. J Thorac Cardiovasc Surg. 2019 Jul;158(1):277-278. doi: 10.1016/j.jtcvs.2019.04.031. Epub 2019 Apr 24. J Thorac Cardiovasc Surg. 2019. PMID: 31103202 No abstract available.

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