A Phase 1 Study of Concurrent Neoadjuvant Pembrolizumab Plus Chemoradiation Followed by Consolidation Pembrolizumab in Patients With Resectable Stage IIIA NSCLC

Introduction: Evidence supports the addition of immuno-therapy to definitive chemoradiation for unresectable stage IIIA NSCLC. Adding pembrolizumab to neoadjuvant che-moradiation in patients with resectable stage IIIA NSCLC requires study for safety and feasibility.Methods: Patients with resectable stage IIIA NSCLC received neoadjuvant cisplatin, etoposide, and pem-brolizumab concurrently with thoracic radiotherapy of 45 Gy in 25 fractions. Patients without progression underwent resection followed by 6 months of consolidation pem-brolizumab. Safety and feasibility were defined as less than or equal to 30% grade 3 or higher pulmonary toxicity or any grade 4 or 5 nonhematologic toxicity. A total of 10 patients were to be enrolled initially. If less than or equal to two patients had events, another 10 were to be enrolled.Results: The study closed after enrolling nine patients. The median age was 66 (range: 49-76) years. A total of 67% were female. Median follow-up was 38.3 months. Serious adverse events occurred in seven patients, including two grade 5 events: one sudden cardiac arrest in the neo-adjuvant phase and one fatal pneumocystis pneumonia after resection. Eight patients were assessable for response. The overall response rate was 67%. Six underwent complete resection. Four achieved pathologic complete response, whereas one additional patient had complete nodal clear-ance. Median progression-free survival has not been reached. The 3-year overall survival was 64%.Conclusions: Adding pembrolizumab to neoadjuvant con-current cisplatin, etoposide, and radiotherapy in resectable stage IIIA NSCLC resulted in an encouraging pathologic complete response rate. Higher-than-expected toxicities necessitated trial closure after meeting the rule for infeasibility. The relationship of grade 5 events to the addition of pembrolizumab is unclear.(c) 2022 The Authors. Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/).