Comparative efficacy of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) monotherapy versus combined EGFR-TKI and chemotherapy in resectable EGFR-mutant non-small cell lung cancer: a real-world multicenter retrospective study

Abstract

Background

While perioperative immunotherapy and adjuvant targeted therapy have improved outcomes for advanced non-small cell lung cancer (NSCLC), evidence on preoperative targeted strategies remains limited. This study retrospectively evaluated the efficacy and safety of neoadjuvant epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy with or without chemotherapy in resectable EGFR-mutant NSCLC.

Methods

Consecutive patients with EGFR-mutant NSCLC undergoing preoperative EGFR-TKI monotherapy or EGFR-TKI plus platinum-based chemotherapy followed by surgical resection were identified from three Chinese thoracic surgery prospectively maintained databases (2010–2023) from Peking University Cancer Hospital, Sun Yat-sen University Cancer Center, and The Affiliated Hospital of Putian University. Primary endpoints included major pathological response (MPR: ≤10% viable tumor) and pathological complete response (pCR). Safety, recurrence-free survival (RFS), and perioperative outcomes were secondary endpoints.

Results

A total of 50 eligible patients were identified, including 29 females (58%) and 21 males (42%). The age range was 38 to 75 years, with an average age of 60 years. Among them, 22 patients (44%) were staged as cII, and 28 patients (56%) were staged as cIII. The EGFR mutations were found in 25 patients (50%) with exon 19 deletions, 21 patients (42%) with exon 21 L858R mutations, and 4 patients (8%) with other mutation types. Sixteen patients (32%) received first-generation TKIs, and 31 patients (62%) received third- generation TKIs. Chemotherapy mainly consisted of pemetrexed combined with carboplatin in 90% of cases. During neoadjuvant therapy, 6% of patients experienced grade 3 or higher adverse events (AEs), all in the combination therapy group. The overall objective response rate (ORR) was 64% (32/50), and 30 patients (60%) experienced a downstage in disease after treatment. The R0 resection rate was 96% (48/50), and 90% underwent video-assisted thoracoscopic surgery (VATS). Seven patients (14%) achieved pCR, and 18 patients (36%) achieved MPR postoperatively. Postoperative MPR and pCR rates were 36.0% (18/50) and 14.0% (7/50), respectively, with higher pCR in the combination group (20% vs. 5%; P=0.22). R0 resection was achieved in 96% (48/50). The overall 3-year RFS rates were 51.3% (53.4% combination vs. 46.7% monotherapy; P=0.42).

Conclusions

Neoadjuvant EGFR-TKI therapy combined with chemotherapy demonstrated promising pathological responses and perioperative safety, supporting its feasibility in resectable EGFR-mutant NSCLC.

Highlight box.

Key findings

• This study demonstrates that preoperative epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) + chemotherapy yielded a significantly higher pathological complete response (pCR) rate than TKI monotherapy (20.0% vs. 5.0%), while major pathological response rates were comparable (36.7% vs. 35.0%). These results extend findings from CTONG1103 (which established neoadjuvant EGFR-TKI’s superiority over chemotherapy alone in event-free survival) by directly comparing TKI-based combination therapy versus TKI alone in resectable EGFR-mutant non-small cell lung cancer.

What is known and what is new?

• Our data support including EGFR-TKI as essential backbone therapy for neoadjuvant treatment in this population. The robust R0 resection rate (96%) and perioperative safety profile (no grade ≥4 adverse events) further validate the feasibility of TKI-containing strategies.

• However, with similar long-term recurrence-free survival (RFS) (3-year RFS: 53.4% combination vs. 46.7% monotherapy; P=0.42), the optimal regimen—TKI monotherapy or combination with chemotherapy—remains unresolved.

What is the implication, and what should change now?

• Clinical decision-making should consider tumor burden (e.g., higher pCR with combination therapy in cN2). Future randomized trials should define patient subgroups benefiting from combination strategies and TKI monotherapy.

Introduction

Over the past two decades, targeted therapy and immunotherapy have profoundly transformed the treatment landscape of advanced non-small cell lung cancer (NSCLC), significantly improving prognosis. For epidermal growth factor receptor (EGFR) mutant NSCLC, the FLAURA2 trial demonstrated that osimertinib combined with platinum-based chemotherapy achieved a higher objective response rate (ORR) compared to single-agent targeted therapy (83% vs. 76%), and a longer median progression-free survival (25.5 vs. 16.7 months) (1). With the success of neoadjuvant/perioperative immunotherapy and postoperative targeted therapy, the importance of perioperative treatment has once again been emphasized (2-6). However, the strategy for neoadjuvant treatment in EGFR mutation-positive NSCLC has remained stagnant, and there is considerable debate over the optimal approach. The CTONG1103 trial, which assessed the efficacy of neoadjuvant targeted therapy versus chemotherapy in resectable EGFR-mutant NSCLC, found no pathological complete response (pCR) in either group, with major pathological response (MPR) rates of 9.7% for targeted therapy and 0 for chemotherapy (7). The CTONG2104 trial, evaluating neoadjuvant immunotherapy in resectable EGFR-mutant NSCLC, reported a single-arm study with four cases approaching pCR (residual cancer <1%), and an MPR of 44% (8/18) (8). In light of these findings, we initiated this multicenter, retrospective study to compare the efficacy of EGFR-tyrosine kinase inhibitor (TKI) monotherapy vs. combined EGFR-TKI and chemotherapy in the neoadjuvant treatment of EGFR-mutant NSCLC. We present this article in accordance with the STROBE reporting checklist (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-283/rc).

Methods

Study population

We extracted data from the prospective lung cancer database of the Department of Thoracic Surgery at Peking University Cancer Hospital, Department of Thoracic Surgery at Sun Yat-sen University Cancer Center, and Department of Cardiothoracic Surgery at The Affiliated Hospital of Putian University, covering consecutive patients who met the following inclusion and exclusion criteria between 2010 and 2023. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Medical Ethics Committee of Peking University Cancer Hospital (No. 2023KT85), Sun Yat-sen University Cancer Center (No. G2023-220-01), and The Affiliated Hospital of Putian University (No. 2025165) and individual consent for this retrospective analysis was waived.

Inclusion criteria:

1. Pathologically confirmed primary NSCLC;

2. Clinical stage cII–III;

3. Presence of EGFR gene mutations;

4. Receipt of at least 4 weeks of neoadjuvant targeted therapy prior to surgery;

5. Intent to undergo radical resection.

Exclusion criteria:

1. Only chemotherapy was administered;

2. No surgical treatment was performed.

Staging methods and follow-up

Standard staging evaluations were conducted within 30 days prior to treatment, including enhanced chest computed tomography (CT), positron emission tomography/computed tomography (PET/CT), and brain magnetic resonance imaging (MRI). For patients unable to undergo MRI, enhanced CT of the brain was used as an alternative. If PET/CT was unavailable, abdominal ultrasound (including liver and adrenal glands) or enhanced CT of the upper abdomen and whole-body bone scanning were performed. For suspicious mediastinal or hilar lymph nodes on CT or PET/CT, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) or other biopsy methods were recommended for pathological confirmation. Staging was based on the 8th edition of the American Joint Committee on Cancer staging system (9).

Indications of neoadjuvant treatment

Neoadjuvant therapy was administered to all patients with clinical lymph nodes stage (cN)2 disease. For patients with cN1 or T2 and N positive, the decision for neoadjuvant treatment was made by a multidisciplinary team (MDT) including oncologists, thoracic surgeons, radiotherapists, and radiologists. Chemotherapy regimens included platinum-based doublet therapy, with drugs chosen based on the patient’s pathological type and investigator’s decision. Options included:

1. Pemetrexed combined with carboplatin: pemetrexed 500 mg/m² on day 1; carboplatin area under the curve (AUC) =5 on day 1, every 21 days;

2. Albumin-bound paclitaxel combined with carboplatin: albumin-bound paclitaxel 260 mg/m² on day 1; carboplatin AUC =5 on day 1, every 21 days.

Targeted therapy drugs include gefitinib, erlotinib, afatinib, osimertinib, almonertinib, and furmonertinib. Adverse events (AEs) from neoadjuvant therapy were assessed according to the Common Terminology Criteria for Adverse Events 5.0 (10).

Re-staging after neoadjuvant therapy

Re-staging was performed within 30 days prior to surgery using enhanced chest CT (PET was used for 29/50 patients). If re-evaluation exceeded 90 days from the initial staging, PET/CT and enhanced brain MRI were re-performed to exclude distant metastasis. For patients with suspected N2 or N3 lymph nodes after neoadjuvant therapy, re-biopsy was conducted for pathological confirmation. Imaging assessments of efficacy were performed using the Response Evaluation Criteria in Solid Tumors 1.1 criteria (11).

Indications and extents for surgical resection

Patients with re-staged I–IIIa disease after neoadjuvant therapy were considered for surgery. N2 patients’ eligibility for surgical resection was determined by the MDT. The primary surgical procedure was lobectomy, though some patients with central tumors received bilobectomy, sleeve lobectomy, or even pneumonectomy. Systematic lymph node dissection was performed, typically including at least three N1 and three N2 stations (station 7 lymph nodes must be included in N2 lymph nodes).

Pathological evaluation

Postoperative tumor pathological regression was assessed according to the International Association for the Study of Lung Cancer (IASLC) criteria, requiring continuous sectioning of all lesions (12,13). Tumor bed was calculated based on areas of tumor, necrosis, and fibrosis. Evaluation was performed by at least two experienced pathologists at each center.

Postoperative treatment principles

The decision for postoperative adjuvant treatment and specific regimens was made by the multidisciplinary team according to current treatment guidelines.

Follow-up methods

In the first two years after surgery, patients were followed every 3 months with blood tests, enhanced chest CT, and abdominal ultrasound (including liver and adrenal glands). Brain MRI was performed every 6–12 months (bone scans were performed as needed). From the 3rd to the 5th year post-surgery, follow-up occurred every 6 months for blood tests, chest CT, and abdominal ultrasound, with annual brain MRI. After 5 years, annual follow-up included blood tests, chest CT, abdominal ultrasound, and brain MRI. For patients unable to undergo MRI, enhanced CT of the brain was substituted.

Study endpoints

The primary endpoint of this study was the MPR rate. Secondary endpoints included pCR rate, perioperative AEs, and long-term survival.

Statistical analysis

Continuous variables were analyzed using independent t-tests, with results presented as medians and interquartile ranges. Categorical variables were analyzed using Chi-squared or Fisher’s exact tests, with results presented as counts and percentages. Survival analysis was performed using Kaplan-Meier curves. Multivariate analysis was conducted using Cox proportional hazards regression models. All tests were two-sided, with α=0.05. Data analysis was performed using R software for Windows, version 4.3.2. The data cutoff date for this report was December 31, 2024.

Results

Baseline characteristics of the study population

A total of 50 patients with NSCLC who underwent neoadjuvant targeted therapy, with or without chemotherapy, followed by surgery, were included in this study. Among them, 21 patients (42.0%) were male, and 29 patients (58.0%) were female. The median age was 60 years, ranging from 38–75 years. Clinical staging was as follows: 22 patients (44%) in stage II and 28 patients (56%) in stage III. EGFR mutations were primarily exon 19 deletions (25 patients, 50.0%), followed by exon 21 L858R mutations (21 patients, 42.0%), and other mutations in 4 patients (8.0%). Detailed baseline characteristics and clinical staging are summarized in Table 1.

Table 1. Baseline characteristics.

Characteristics	T + C (N=30)	T (N=20)	P
Age (years)	59.1	62.6	0.22
Sex			0.52
Male	11 (36.7)	10 (50.0)
Female	19 (63.3)	10 (50.0)
Smoking status			0.19
Ever	23 (76.7)	11 (55.0)
Never	7 (23.3)	9 (45.0)
ECOG performance status			0.29
0	23 (76.7)	18 (90.0)
1	7 (23.3)	2 (10.0)
Histological			0.51
ADC	28 (93.3)	20 (100.0)
SCC	2 (6.7)	0
Tumor location			0.02
Right upper lobe	11 (36.7)	5 (25.0)
Right middle lobe	7 (23.3)	1 (5.0)
Right lower lobe	0	5 (25.0)
Left upper lobe	5 (16.7)	6 (30.0)
Left lower lobe	7 (23.3)	3 (15.0)
EGFR mutation			0.94
Exon 19 deletion	16 (53.3)	9 (45.0)
L858R	12 (40.0)	9 (45.0)
Exon 20 ins	1 (3.3)	1 (5.0)
G719X	1 (3.3)	1 (5.0)
cT			0.37
cT1	5 (16.7)	5 (25.0)
cT2	19 (63.3)	9 (45.0)
cT3	5 (16.7)	3 (15.0)
cT4	1 (3.3)	3 (15.0)
cN			0.03
cN0	2 (6.7)	5 (25.0)
cN1	10 (33.3)	10 (50.0)
cN2	18 (60.0)	5 (25.0)
Clinical stage			0.12
cII	10 (33.3)	12 (60.0)
cIII	20 (66.7)	8 (40.0)

The age was presented as an average; other data were presented as number of patients (%). ADC, adenocarcinoma; cN, clinical lymph nodes stage; cT, clinical tumor stage; ECOG, Eastern Cooperative Oncology Group; EGFR, epidermal growth factor receptor; SCC, squamous cell carcinoma; T, TKI monotherapy group; T + C, TKI plus chemotherapy group; TKI, tyrosine kinase inhibitor.

Neoadjuvant treatment regimens

Of the 50 patients, 30 received neoadjuvant chemotherapy combined with EGFR-TKI. Among these, 10 patients (33.3%) were treated with first-generation TKIs, 1 patient (3.3%) received second-generation TKIs, and 19 patients (63.3%) received third-generation TKIs. The duration of targeted therapy ranged from 1 to 11 months. Neoadjuvant chemotherapy was administered in 1 to 4 cycles, with 96.7% of patients receiving 2–4 cycles. The most commonly used chemotherapy regimen was pemetrexed combined with a platinum-based agent (90%).

Twenty patients received EGFR-TKI monotherapy including 7 patients (35.0%) treated with first-generation TKIs, 2 patients (10.0%) with second-generation TKIs, and 11 patients (55.0%) with third-generation TKIs. The duration of drug exposure ranged from 2 to 17 months, with a median treatment duration of 3 months.

AEs of grade 3 or higher occurred in 3 patients (6.0%), all of whom were in the combination group. The AEs included thrombocytopenia (2 cases, 4.0%) and neutropenia (1 case, 2.0%). No treatment-related deaths were reported.

Surgical outcomes

All patients underwent surgery with the intent for radical resection (Table 2). A total of 48 patients (96.0%) achieved R0 resection, while 2 patients (4.0%) had R2 resection due to intraoperative pleural dissemination-one in the single-target therapy group and the other in the combination group. Forty-five patients (90.0%) underwent video-assisted thoracoscopic surgery (VATS), and 5 patients (10.0%) underwent thoracotomy, (all of which occurred within the chemotherapy plus targeted therapy group), with no conversions to thoracotomy during VATS. Forty-five patients (90.0%) underwent lobectomy, including 6 patients (12.0%) who had bilobectomy and 1 patient (2.0%) who underwent sleeve resection. Systematic lymph node dissection was performed in 46 patients (92.0%), with 3 patients (6.0%) undergoing lobe-specific lymph node dissection and 1 patient (2.0%) undergoing lymph node sampling. The average surgical duration for the cohort was 108 minutes, with a mean blood loss of 50 mL.

Table 2. Neoadjuvant treatment and surgical outcomes.

Characteristics	T + C (N=30)	T (N=20)	P
TKI generation			0.65
1st generation	10 (33.3)	7 (35.0)
2nd generation	1 (3.3)	2 (10.0)
3rd generation	19 (63.3)	11 (55.0)
TKI time (months)	2.87	4.30	0.12
Chemotherapy cycles			<0.001
0	0	20 (100.0)
1	1 (3.3)	0
2	16 (53.3)	0
3	6 (20.0)	0
4	7 (23.3)	0
Radiologic response			0.31
PR	17 (56.7)	15 (75.0)
SD	13 (43.3)	5 (25.0)
Downstaging			0.38
Yes	20 (66.7)	10 (50.0)
No	10 (33.3)	10 (50.0)
MPR			>0.99
Yes	11 (36.7)	7 (35.0)
No	19 (63.3)	13 (65.0)
pCR			0.22
Yes	6 (20.0)	1 (5.0)
No	24 (80.0)	19 (95.0)
Surgical approach			0.15
VATS	25 (83.3)	20 (100.0)
Thoracotomy	5 (16.7)	0
Extent of resection			0.09
Lobectomy	29 (96.7)	16 (80.0)
Segmentectomy	0	3 (15.0)
Wedge resection	1 (3.3)	1 (5.0)
Duration from clinic to surgery (months)	3.48 [2.66, 4.29]	3.45 [3.02, 5.18]	0.49
Operation time (min)	109 [84.3, 144.8]	103 [79.8, 124.0]	0.31
Blood loss (mL)	50 [50.0, 100.0]	50 [50.0, 100.0]	0.87

Data are presented as mean for TKI time, median [IQR] for the duration from clinic to surgery and blood loss, mean [IQR] for operation time, and n (%) for all other variables. IQR, interquartile range; MPR, major pathological response; pCR, pathological complete response; PR, partial response; SD, stable disease; T, TKI monotherapy group; T + C, TKI plus chemotherapy group; TKI, tyrosine kinase inhibitor; VATS, video-assisted thoracoscopic surgery.

Short-term outcomes

Based on imaging assessments, the ORR was 64.0% (32/50), with 30 patients (60.0%) achieving downstaging after treatment. Among them, 27 patients had T downstaging, and 25 patients had N downstaging. Of the 23 patients with N2 disease, 12 (52.2%) achieved downstaging, as shown in Figure 1 and Appendix 1.

Figure 1.

Lymph nodes status at baseline and post-surgery. cN, clinical lymph nodes stage; ypN, post-therapy pathological nodal stage.

Postoperative assessment of the entire cohort revealed that 18 patients (36.0%) achieved MPR, and 7 patients (14.0%) achieved pCR. Among the pCR patients, 6 (20.0%, 6/30) were from the targeted therapy combined with chemotherapy group. Postoperative pathological staging showed 7 patients (14.0%) in yp0 stage, 15 patients (30.0%) in ypIA, 4 patients (8.0%) in ypIB, 2 patients (4.0%) in ypIIA, 5 patients (10.0%) in ypIIB, 15 patients (30.0%) in ypIIIA, and 2 patients (4.0%) in ypIVA, as shown in the waterfall plot (Figure 2).

Figure 2.

Depth of pathological regression in primary tumor. Dashed black line represents major pathologic response. EGFR, epidermal growth factor receptor; MPR, major pathological response; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors; SD, stable disease; TKI, tyrosine kinase inhibitor.

There were no perioperative complications or treatment-related deaths observed in the cohort. Of the 50 patients, 80.0% (40/50) received adjuvant targeted therapy postoperatively. In the monotherapy group, 2 patients received postoperative radiotherapy, while in the combination group, 3 patients received postoperative chemotherapy.

Long-term outcomes and patterns of disease progression

The median follow-up time for the whole cohort was 32.4 months. The 1-year disease-free survival (DFS) rate was 96%, the 2-year DFS rate was 82.3%, and the 3-year DFS rate was 51.3%. In the combination group, the 1-, 2-, and 3-year DFS rates were 100%, 81.3%, and 53.4%, respectively. In the monotherapy group, the 1-, 2-, and 3-year DFS rates were 90%, 84%, and 46.7%, as illustrated in Figure 3. Cox proportional hazards regression models are shown in Figure 4.

Figure 3.

Kaplan-Meier estimates of disease-free survival (DFS). DFS was defined as the time from curative surgery to recurrence, progression or death.

Figure 4.

Forest plot of hazard ratios for prognostic factors in the whole cohort. CI, confidence interval; EGFR, epidermal growth factor receptor; HR, hazard ratio; MPR, major pathological response; T, TKI monotherapy group; T + C, TKI plus chemotherapy group; TKI, tyrosine kinase inhibitor.

A total of 18 patients (36.0%) experienced recurrence, with 8 patients (40.0%) in the monotherapy group and 10 patients (33.3%) in the combination group. Distant metastasis was the predominant type of relapses (15/18), including brain metastasis in 6 patients, lung metastasis in 5 patients, pleural metastasis in 2 patients, bone metastasis in 1 patient, and abdominal wall metastasis in 1 patient. Additionally, 2 patients had supraclavicular lymph node metastasis, and 1 patient had mediastinal lymph node metastasis. All patients with recurrence received treatment after progression. Notably, no patients with recurrence or metastasis died due to disease progression.

Discussion

Substantial evidence suggests that NSCLC is a systemic disease, and even patients with early-stage disease require appropriate perioperative treatment to achieve better long-term survival. This concept has been widely accepted since the chemotherapy era, with increasing attention directed toward preoperative treatment due to its various advantages. However, the efficacy of perioperative treatment during the chemotherapy era was suboptimal. With advancements in the understanding of NSCLC driver mutations, the discovery of the programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) pathway, and the successful development of drugs targeting these pathways, the prognosis of advanced NSCLC has been markedly improved, and perioperative treatment for resectable NSCLC has made significant strides. Neoadjuvant chemotherapy combined with PD-1/PD-L1 inhibitors has become the standard for preoperative treatment in resectable NSCLC.

Nevertheless, the efficacy of this treatment strategy in EGFR mutation-positive NSCLC has been contentious. As a result, most large perioperative immunotherapy trials (such as Checkmate 816, KeyNote671, AEGEAN, Neotorch, etc.) have excluded patients with EGFR and other driver gene mutations (3-6). The data from the Pacific trial also confirmed that maintenance immunotherapy following definitive chemoradiotherapy yielded minimal benefit for EGFR mutation-positive patients (14). However, a prospective study by Zhang et al. evaluating neoadjuvant chemotherapy combined with immunotherapy for EGFR mutation-positive NSCLC found that, although pCR was not achieved, the MPR rate reached as high as 44%, comparable to the outcomes observed in EGFR wild-type NSCLC treated with neoadjuvant chemotherapy + immunotherapy (15). Similarly, Zhang et al. in a multicenter retrospective study demonstrated that in EGFR mutation-positive resectable NSCLC patients who received neoadjuvant chemotherapy plus immunotherapy, the pCR rate was 12.5%, with an MPR rate of 37.5% (8).

Despite these findings, the ADAURA and LAURA trials showed that postoperative and chemoradiotherapy-based adjuvant targeted therapy significantly improved survival in NSCLC patients, reinforcing the continued investigation into preoperative targeted therapy. The critical theoretical advantage of systemic induction treatment prior to local therapy is that, in addition to improving survival, it facilitates tumor downstaging, thereby potentially reducing the extent of local treatments (surgery/radiotherapy).

Although the only existing randomized controlled trial (RCT), CTONG1103, demonstrated a pCR rate of 0% and an MPR rate of only 9.7% after erlotinib monotherapy (7), a phase II single-arm study by Zhang et al. of neoadjuvant gefitinib treatment reported a pCR rate of 12.1% (4/33) and an MPR rate of 24.2% (16). The ASCENT phase II clinical study found that after afatinib combined with chemoradiotherapy in 19 EGFR mutation-positive NSCLC patients, 10 patients who underwent surgery achieved a pCR rate of 10.0% (1/10), with an MPR rate of 60.0% (6/10) (17). Furthermore, several other retrospective or phase II single-arm clinical studies have shown that osimertinib monotherapy in neoadjuvant treatment for NSCLC produced pCR rates ranging from 0% to 5.9%, and MPR rates between 10.7% and 24% (18-21). In the present study, 50 patients with EGFR mutation-positive NSCLC who underwent surgery after targeted therapy, with or without chemotherapy, demonstrated a pCR rate of 14.0% (7/50) and an MPR rate of 36.0% (18/50). Specifically, the pCR rates in the monotherapy and combination therapy groups were 5.0% (1/20) and 20.0% (6/30), while the MPR rates were 35.0% (7/20) and 36.7% (11/30), respectively.

The necessity of maintaining targeted therapy after radical resection in patients who have undergone neoadjuvant targeted therapy is a significant clinical issue. In the CTONG1103 trial, patients who received postoperative adjuvant targeted therapy for 1 year showed median event-free survival (EFS) of 21.5 and 11.4 months (7). Similarly, the design of NeoADAURA included 3 years of adjuvant targeted therapy. In our cohort, 80% of patients received postoperative adjuvant targeted therapy (22). Although this study did not observe a difference in recurrence between adjuvant therapy and no adjuvant therapy, which may be related to insufficient sample size, we still believe that postoperative adjuvant targeted therapy is necessary.

Whether neoadjuvant targeted therapy increases the difficulty of surgery is another topic of interest. Previous studies have suggested an increased incidence of atrial fibrillation and chylothorax in the perioperative period following neoadjuvant targeted therapy (23). However, our data do not support this hypothesis. In our cohort, 90% of patients successfully underwent surgery via VATS, and the surgical duration, intraoperative blood loss, and incidence of postoperative complications were similar to those observed in patients who did not receive neoadjuvant therapy.

There are some limitations in this study. It is a retrospective study, and as such, is inevitably subject to selection bias. Although data were collected from three centers, the sample size remains relatively small. The types of TKI drugs used and their treatment durations were not consistent across the cohort. Additionally, the re-staging strategies after neoadjuvant therapy prior to surgery varied among the three centers, which may have resulted in inconsistencies in staging diagnoses. While MPR and pCR were assessed using standardized criteria, they were not subject to independent review or re-evaluation.

Conclusions

This study demonstrates that the strategy of surgery after neoadjuvant targeted therapy combined with chemotherapy for EGFR mutation-positive NSCLC shows promising efficacy. The use of targeted therapy or targeted therapy combined with chemotherapy in the perioperative period is safe and feasible.

Supplementary

The article’s supplementary files as

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Medical Ethics Committee of Peking University Cancer Hospital (No. 2023KT85), Sun Yat-sen University Cancer Center (No. G2023-220-01), and The Affiliated Hospital of Putian University (No. 2025165) and individual consent for this retrospective analysis was waived.

Data Sharing Statement

Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-283/dss

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DOI: 10.21037/tlcr-2025-283