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

Matthew J. Bott, Stephen C Yang, Bernard J. Park, Prasad S. Adusumilli, Valerie W. Rusch, James M. Isbell, Robert J. Downey, Julie Brahmer, Richard J Battafarano, Errol Bush, Jamie Chaft, Patrick Forde, David R. Jones, Stephen Broderick

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalJournal of Thoracic and Cardiovascular Surgery
DOIs
StateAccepted/In press - Jan 1 2019

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Non-Small Cell Lung Carcinoma
Lung
Video-Assisted Thoracic Surgery
Neoadjuvant Therapy
Robotics
Thoracotomy
Programmed Cell Death 1 Receptor
Length of Stay
Morbidity
Safety
Pneumonectomy
Mortality
Operative Time
nivolumab
Cardiac Arrhythmias
Fibrosis
Monoclonal Antibodies
Tomography
Inflammation
Therapeutics

Keywords

  • immune checkpoint inhibition
  • immunotherapy
  • neoadjuvant
  • NSCLC

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Initial results of pulmonary resection after neoadjuvant nivolumab in patients with resectable non–small cell lung cancer. / Bott, Matthew J.; Yang, Stephen C; Park, Bernard J.; Adusumilli, Prasad S.; Rusch, Valerie W.; Isbell, James M.; Downey, Robert J.; Brahmer, Julie; Battafarano, Richard J; Bush, Errol; Chaft, Jamie; Forde, Patrick; Jones, David R.; Broderick, Stephen.

In: Journal of Thoracic and Cardiovascular Surgery, 01.01.2019.

Research output: Contribution to journalArticle

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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.",
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T1 - Initial results of pulmonary resection after neoadjuvant nivolumab in patients with resectable non–small cell lung cancer

AU - Bott, Matthew J.

AU - Yang, Stephen C

AU - Park, Bernard J.

AU - Adusumilli, Prasad S.

AU - Rusch, Valerie W.

AU - Isbell, James M.

AU - Downey, Robert J.

AU - Brahmer, Julie

AU - Battafarano, Richard J

AU - Bush, Errol

AU - Chaft, Jamie

AU - Forde, Patrick

AU - Jones, David R.

AU - Broderick, Stephen

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N2 - 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.

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KW - neoadjuvant

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