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. 2021 Jan 12:10:586596.
doi: 10.3389/fonc.2020.586596. eCollection 2020.

Neoadjuvant EGFR-TKI Therapy for EGFR-Mutant NSCLC: A Systematic Review and Pooled Analysis of Five Prospective Clinical Trials

Li Sun  1 , Yi-Jia Guo  1 , Jun Song  1 , Yan-Ru Wang  1 , Shu-Ling Zhang  1 , Le-Tian Huang  1 , Jian-Zhu Zhao  1 , Wei Jing  1 , Cheng-Bo Han  1 , Jie-Tao Ma  1
Affiliations

Neoadjuvant EGFR-TKI Therapy for EGFR-Mutant NSCLC: A Systematic Review and Pooled Analysis of Five Prospective Clinical Trials

Li Sun et al. Front Oncol. .

Abstract

Purpose: The role of neoadjuvant epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) targeted therapy for patients with EGFR-mutant non-small cell lung cancer (NSCLC) has not been clarified. A pooled analysis of prospective clinical trials was conducted to evaluate the efficacy and safety of neoadjuvant EGFR-TKI therapy.

Methods: The PubMed, Embase, Web of Science, and Cochrane Library databases, as well as meeting abstracts were searched for prospective clinical trials evaluating the efficacy and safety of neoadjuvant EGFR-TKI for treatment of EGFR-mutant NSCLC. The main outcomes included the objective response rate (ORR), downstaging rate, surgical resection rate (SRR), pathologic complete response (pCR) rate, progression-free survival (PFS), and adverse events.

Results: A total of five, phase II, prospective, clinical trials involving 124 patients with resectable or potentially resectable EGFR-mutant NSCLC treated with neoadjuvant erlotinib or gefitinib treatment were included in this pooled analysis. The median neoadjuvant medication time was 42 (range, 21-56) days and the median time of response evaluation was 45 (range, 42-56) days. The pooled ORR was 58.5% [95% confidence interval (CI), 45.5%-71.8%] and the surgical resection and complete resection (R0) rates were 79.9% (95% CI, 65.3%-94.5%) and 64.3% (95% CI, 43.8%-84.8%), respectively. In the stage IIIA subgroup (n = 68), the pooled ORR, SRR, and R0 rate were 51.4%, 72.9%, and 57.0%, respectively, while the downstaging and pCR rates were 14.0% and 0.0%, respectively. The pooled median PFS and overall survival were 13.2 and 41.9 months, respectively. Of the most common grade 3/4 adverse events in the overall group, the incidences of hepatotoxicity and skin rash were 5.3% and 14.7%, respectively. The most commonly reported postoperative complications were lung infection, arrhythmia, and pneumothorax.

Conclusion: Neoadjuvant EGFR-TKI therapy provides a feasible treatment modality for patients with resectable or potentially resectable EGFR-mutant NSCLC, with satisfactory surgical outcomes and low toxicity. Although further phase III clinical trials are needed to confirm these findings, it is necessary to explore the feasibility of a more effective EGFR-TKI combination neoadjuvant therapy given the modest downgrade and pCR rates for EGFR-TKI alone.

Keywords: efficacy; epidermal growth factor receptor-tyrosine kinase inhibitors; neoadjuvant; non-small cell lung cancer; safety.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
A flow diagram of the literature search and selection process.
Figure 2
Figure 2
The pooled efficacy rates in the overall group. The ORR (A); SRR (B); and R0 resection rate (C).
Figure 3
Figure 3
The pooled efficacy rates in the stage IIIA subgroup. The ORR (A); SRR (B); R0 resection rate (C); and downstaging rate (D).
Figure 4
Figure 4
Median PFS of the stage IIIA subgroup.
Figure 5
Figure 5
Sensitivity analyses (A) and funnel plot (B) of the ORR among the included studies.
See this image and copyright information in PMC

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