Gefitinib as neoadjuvant therapy for resectable stage II-IIIA non-small cell lung cancer: A phase II study

Yang Zhang; Fangqiu Fu; Haichuan Hu; Shengping Wang; Yuan Li; Hong Hu; Haiquan Chen

doi:10.1016/j.jtcvs.2020.02.131

Gefitinib as neoadjuvant therapy for resectable stage II-IIIA non-small cell lung cancer: A phase II study

J Thorac Cardiovasc Surg. 2021 Feb;161(2):434-442.e2. doi: 10.1016/j.jtcvs.2020.02.131. Epub 2020 Mar 19.

Authors

Yang Zhang¹, Fangqiu Fu¹, Haichuan Hu¹, Shengping Wang², Yuan Li³, Hong Hu¹, Haiquan Chen⁴

Affiliations

¹ Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Institute of Thoracic Oncology, Fudan University, Shanghai, China; State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
² Institute of Thoracic Oncology, Fudan University, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China.
³ Institute of Thoracic Oncology, Fudan University, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
⁴ Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Institute of Thoracic Oncology, Fudan University, Shanghai, China; State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: [email protected].

PMID: 32340810
DOI: 10.1016/j.jtcvs.2020.02.131

Abstract

Introduction: Currently, limited data on tyrosine kinase inhibitors as neoadjuvant therapy exist. This prospective study aimed to investigate the efficacy and safety of preoperative gefitinib in patients with stage II-IIIA operable non-small cell lung cancer (NSCLC).

Methods: This was a single-arm, phase II trial performed in the Shanghai Cancer Center. Between August 2013 and October 2015, patients with operable stage II-IIIA NSCLC with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R mutation were enrolled. Patients were treated with preoperative gefitinib (250 mg once daily for 42 days), followed by surgical resection. The primary endpoint was objective response rate (ORR); secondary endpoints were the rate of major pathologic response (MPR), disease-free survival (DFS), overall survival, and adverse events (AEs). ORR was defined as the proportion of patients achieving complete response or partial response radiologically. MPR was defined as no more than 10% viable tumor.

Results: Of the 35 eligible patients, 33 were considered as intention-to-treat population. ORR, the primary endpoint, was 54.5% (95% confidence interval [CI], 37.7-70.7), and the rate of MPR was 24.2% (95% CI, 11.9-40.4). Median DFS was 33.5 months (95% CI, 19.7-47.3); median overall survival was not reached. Skin toxicity (24/35,68.6%) and gastrointestinal symptoms (17/35,48.6%) were the most common AEs; no patients reported grade 3 or 4 AEs. After surgery, 4 patients experienced chylothorax (4/33,12.1%). Patients with MPR had a prolonged survival compared with those without (DFS, P = .019).

Conclusions: Neoadjuvant therapy with gefitinib in patients with stage II-IIIA NSCLC is safe and may be a viable treatment for patients whose tumors have EGFR mutations. Patients with MPR were associated with improved survival.

Keywords: epidermal growth factor receptor; gefitinib; neoadjuvant therapy; non–small cell lung carcinoma.

Publication types

Clinical Trial, Phase II

MeSH terms

Adult
Aged
Antineoplastic Agents / therapeutic use*
Carcinoma, Non-Small-Cell Lung / mortality
Carcinoma, Non-Small-Cell Lung / pathology
Carcinoma, Non-Small-Cell Lung / therapy*
Combined Modality Therapy
Disease-Free Survival
Female
Gefitinib / therapeutic use*
Humans
Kaplan-Meier Estimate
Lung Neoplasms / mortality
Lung Neoplasms / pathology
Lung Neoplasms / therapy*
Male
Middle Aged
Neoadjuvant Therapy* / methods
Pneumonectomy
Survival Analysis

Substances

Antineoplastic Agents
Gefitinib