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

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 videoassisted 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.

Surgical outcomes of segmental bronchial sleeve resection in central non‐small cell lung cancer

“…However, the benefit of this strategy in patients with resectable NSCLC remains unknown. Previous studies have shown that neoadjuvant therapy may cause hilar inflammation and fibrosis, which will increase surgical difficulties. For patients with resectable NSCLC who need sleeve resection, it may be better to perform surgical treatment followed by adjuvant treatment.…”

A year at the forefront of general thoracic surgery

“…22 Neoadjuvant checkpoint inhibitor clinical trials have since become commonplace in academic centers, and thoracic surgeons are more frequently performing operations in patients after immunotherapy. One of the first articles on the safety of lobectomy after checkpoint inhibition is by Bott and colleagues, 23 published in the Journal in December of 2018, and is expected to prove a valuable resource for practicing thoracic surgeons. In the year ahead, we can expect to see the results of the ongoing investigation of checkpoint blockade for early-stage NSCLC brought to the readership of the Journal through Original Research and Feature Expert Opinion articles.…”

Commentary: Neoadjuvant checkpoint inhibitors in resectable non–small cell lung cancer—Ready for prime time?

“…The trial demonstrated an unprecedented 45% major pathologic response (MPR) rate after only 2 cycles of nivolumab before surgery. Surgical outcomes of this trial were published by Bott and colleagues, 8 who highlighted that there were no delays in resections, morbidity outcomes were comparable to those of neoadjuvant chemotherapy regimens, and, perhaps most importantly, a 54% (7/13) conversion rate was seen from either a video-assisted thoracoscopic surgery or a robotic-assisted thoracoscopic surgery initial approach to thoracotomy in response to an ''inflamed hilum.'' Communications among thoracic surgeons about anecdotal cases of inflammation after immunotherapy suggest that operating on patients in this setting is perhaps technically more challenging than operating primarily on early lung cancer.…”

“…Importantly, though, perioperative outcomes are not negatively affected by this slightly increased technical challenge. 8 The inflammatory reaction to ICIs appears to be idiosyncratic, and we currently do not have biomarkers that can predict intraoperative inflammation before surgical inspection of the pleural space.…”