Salvage surgery for non-small cell lung cancer after tyrosine kinase inhibitor treatment

Abstract

Objectives: The prognostic impact of surgical intervention for recurrent or residual non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) rearrangement after tyrosine-kinase inhibitor (TKI) treatment remains unclear. We aimed to describe the characteristics and outcomes of patients undergoing salvage surgery in this setting.

Methods: We retrospectively collected and analyzed nationwide Japanese data on perioperative and postoperative outcomes of patients who underwent salvage surgery after EGFR or ALK-TKI during 2010-2015. The primary endpoint was a 3-year overall survival (OS) rate and secondary endpoints were the rate of adverse events, perioperative mortality rate, 3-year recurrence-free survival (RFS) rate, and median survival time after salvage lung resection. Univariate and multivariate analyses were performed to identify independent prognostic factors of OS and RFS.

Results: Thirty-six patients were included (EGFR-TKI: 33, ALK-TKI: 3). The 3-year OS and RFS after the surgery were 75.1 % (95 % confidence interval [CI] 55.9-86.9 %) and 22.2 % (95 % CI 8.6-39.7 %), respectively. Of clinicopathological factors, the progression of disease while on TKI and preoperative carcinoembryonic antigen (CEA) levels (≥5 ng/mL) were shown to be worse independent prognosticators of OS (hazard ratio [HR] 9.38, 95 % CI 1.57-55.88, P = .014; HR 4.84, 95 % CI 1.62-14.46, P = .005, respectively). Older age at initial treatment (≥70 years) and advanced pathological T stage (T2-T4) were the worse prognosticators for RFS (HR 12.58, 95 % CI 2.51-62.97, P = .002; HR 3.06, 95 % CI 1.04-9.03, P = .043, respectively). Grade 3 adverse events occurred in 5.6 % (2/36) patients, but no deaths were reported within 90 days after surgery.

Conclusion: Our study showed that salvage surgery after TKI treatment was safe and feasible and may contribute to prolonged OS time by reducing the local tumor burden.

Keywords: Anaplastic lymphoma kinase; Conversion therapy; Epidermal growth factor receptor; Non-small cell lung cancer; Salvage surgery; Tyrosine kinase inhibitor.