Real-world clinical outcomes of neoadjuvant immunotherapy combined with chemotherapy in resectable non-small cell lung cancer

Junqi Wu; Likun Hou; Haoran E; Yue Zhao; Xin Yu; Long Xu; Ye Ning; Jiajun Deng; Ke Sun; Jie Zhang; Chunyan Wu; Yuming Zhu; Deping Zhao; Yunlang She; Chunxia Su; Chang Chen

doi:10.1016/j.lungcan.2022.01.019

Real-world clinical outcomes of neoadjuvant immunotherapy combined with chemotherapy in resectable non-small cell lung cancer

Lung Cancer. 2022 Mar:165:115-123. doi: 10.1016/j.lungcan.2022.01.019. Epub 2022 Jan 29.

Authors

Junqi Wu¹, Likun Hou², Haoran E¹, Yue Zhao¹, Xin Yu³, Long Xu¹, Ye Ning¹, Jiajun Deng¹, Ke Sun⁴, Jie Zhang³, Chunyan Wu², Yuming Zhu¹, Deping Zhao¹, Yunlang She⁵, Chunxia Su⁶, Chang Chen⁷

Affiliations

¹ Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, People's Republic of China.
² Department of Pathology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, People's Republic of China.
³ Department of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, People's Republic of China.
⁴ Department of Radiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, People's Republic of China.
⁵ Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, People's Republic of China. Electronic address: sylxan3344@163.com.
⁶ Department of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, People's Republic of China. Electronic address: susu_mail@126.com.
⁷ Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, People's Republic of China; Department of Thoracic Surgery, The First Hospital of Lanzhou University, Gansu, China; The International Science and Technology Cooperation Base for Development and Application of Key Technologies in Thoracic Surgery, Gansu Province, China. Electronic address: chenthoracic@163.com.

PMID: 35123154
DOI: 10.1016/j.lungcan.2022.01.019

Abstract

Objectives: Early stage non-small cell lung cancer (NSCLC) patients who undergo complete resection continue to demonstrate high risk of recurrence and death. The advent of the neoadjuvant regimen has brought new hope for these patients. The present study aims to further demonstrate the efficacy of neoadjuvant chemoimmunotherapy.

Materials and methods: A real-world observational study was conducted concerning patients who received neoadjuvant pembrolizumab or nivolumab combined with chemotherapy between January 2018 and December 2020 in Shanghai Pulmonary Hospital. The primary endpoint was major pathologic response (MPR), and the secondary endpoints were objective response rate (ORR), pathologic complete response (pCR), disease-free survival (DFS) and toxicity.

Results: A total of 76 patients were analyzed and divided into the pembrolizumab (n = 42) and nivolumab groups (n = 34) with a median follow-up time of 12.2 months. Most patients (92%) had stage III disease, with 41 (54%) and 29 (38%) patients initially diagnosed clinical stage IIIA and IIIB, respectively. Fifty (66%), 21 (28%) and 5 (6%) patients received two, three and four cycles of neoadjuvant treatment, separately, achieving an ORR of 75%. None of them needed a reduced initial dose or delay due to intolerable adverse events. Forty-nine (64%) and 28 (37%) patients achieved MPR and pCR, respectively. RNA sequencing showed that MPR associated with increased infiltration of cytotoxic immune cells with tertiary lymphoid structures (TLSs). Histological evaluation highlighted the localization of B cells within TLSs. Forty-two (69%) patients with clinically N2 disease at baseline were downstaged to pathological N0 (39 patients) or N1 (3 patients). One-year-PFS rate of stage III patients was 91%. No difference in baseline characteristics and treatment outcomes was observed between 2 groups.

Conclusion: The feasibility of neoadjuvant chemoimmunotherapy for resectable NSCLC was further validated, with a high MPR rate and manageable adverse events.

Keywords: Chemoimmunotherapy; Neoadjuvant; Non-small cell lung cancer.