Efficacy of erlotinib as neoadjuvant regimen in EGFR-mutant locally advanced non-small cell lung cancer patients

Abstract

Background: The optimal neoadjuvant regimen for locally advanced resectable non-small cell lung cancer (NSCLC) remains controversial. EGFR inhibitors have significantly improved survival in patients with EGFR-mutant advanced NSCLC. However, their efficacy in neoadjuvant settings, particularly for treating locally advanced NSCLC, remains unclear. We compared the clinical benefits of chemotherapy and erlotinib as neoadjuvant therapy for stage IIIA NSCLC.

Method: Thirty-one treatment-naïve Chinese patients with stage IIIA NSCLC were enrolled. Patients without EGFR mutation received cisplatin-based doublet chemotherapy (n = 16; N-chemo group) while EGFR-mutant patients received erlotinib (n = 15; N-TKI group) as neoadjuvant therapy.

Results: After completing neoadjuvant treatment, 12 and 8 patients from the N-TKI and N-chemo groups underwent surgery, respectively. Our data revealed that patients who received erlotinib had a marginally better clinical objective response rate (67% vs. 19%), pathological response rate (67% vs. 38%), and overall survival (51.0 months vs. 20.9 months) compared with those who received chemotherapy. Furthermore, patients in the N-TKI group had a significantly greater reduction in tumor diameter, serum carcinoembryonic level, and maximum allelic fraction.

Conclusion: Our findings demonstrate that erlotinib is an effective neoadjuvant regimen in patients with EGFR-mutant locally advanced NSCLC, paving the way for its extended use in neoadjuvant settings.[ClinicalTrials.gov identifier: NCT01217619].

Keywords: Adenocarcinoma; EGFR-TKI; chemotherapy; erlotinib; locally advanced; neoadjuvant; stage IIIA.

Conflict of interest statement

H. Han-Zhang, A. Lizaso, and B. Li are employees of Burning Rock Biotech. The other authors declare no conflicts of interest.

Figures

Figure 1.

Schematic diagram of the study design. Paired baseline blood and tumor tissue samples were obtained from each patient. The neoadjuvant treatment regimen was assigned based on EGFR mutation status. After the completion of neoadjuvant treatment, pre-surgical evaluation was conducted. Paired blood and tumor tissue samples were obtained from patients who underwent surgery. Post-surgery evaluations were conducted every 3 months. Abbreviations: NSCLC, non-small cell lung cancer; N-chemo, neoadjuvant chemotherapy group; N-TKI, neoadjuvant EGFR-tyrosine kinase inhibitor (TKI); ARMS-PCR, amplification refractory mutation polymerase chain reaction; EGFR −, wild-type EGFR; EGFR +, EGFR mutant; EGFR-TKI, EGFR tyrosine kinase inhibitor; EBUS, endobronchial ultrasonography; CT-scan, computed tomography scan; RECIST, Response Evaluation Criteria in Solid Tumors.

Figure 2.

Clinical responses to neoadjuvant treatment. (a). EGFR-TKI neoadjuvant therapy provides better clinical responses compared with chemotherapy. Post-neoadjuvant therapy objective response rate (ORR) for N-chemo and N-TKI groups. Cyan represents the number of patients with SD. Blue represents the number of patients who achieved PR. Orange represents patients whose best response was evaluated as PD. (b)–(c). EGFR-TKI neoadjuvant therapy significantly reduces tumor diameter. (b). Average tumor diameter for patients in each treatment regimen. (c). Average changes in tumor diameter. p-values were calculated using a t-test. (d). EGFR-TKI neoadjuvant therapy significantly reduces maximum allele fraction (maxAF). MaxAF detected in tumor biopsy samples at baseline and surgically resected tumor specimens post-neoadjuvant therapy in the N-chemo and N-TKI groups. Absolute levels of maxAF. A t-test was used to calculate statistical significance. (e)–(f). Serum carcinoembryonic antigen (CEA) levels were significantly reduced in patients who received neoadjuvant EGFR-TKI therapy. (e). Absolute serum CEA levels (ng/ml). F. Ratio of serum CEA after neoadjuvant therapy relative to baseline. Abbreviations: N-chemo, neoadjuvant chemotherapy group; N-TKI, neoadjuvant EGFR-tyrosine kinase inhibitor (TKI); ORR, overall objective response rate; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; CEA, carcinoembryonic antigen.

Figure 3.

Kaplan–Meier estimation of the survival of neoadjuvant-treated patients. (a)–(c). Analysis of progression-free survival (PFS) (a), disease-free survival (DFS) (b), and overall survival (OS) (c) for resected, neoadjuvant chemotherapy, and erlotinib-treated patients. (d)–(e). Analyses of recurrence-free survival (RFS) (d) and overall survival (OS) (e) in chemotherapy-treated patients with or without subsequent surgery. Abbreviations: N-chemo, neoadjuvant chemotherapy group; N-TKI, neoadjuvant EGFR-tyrosine kinase inhibitor (TKI); DFS, disease-free survival; OS, overall survival; RFS, recurrence-free survival.