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

Sun, Li; Guo, Yingying; Song, Jun; Wang, Yanru; Zhang, Shuling; Huang, Le-Tian; Zhao, Jing; Wei, Jing; Han, Cheng-Bo; Ma, Jie-Tao

doi:10.3389/fonc.2020.586596

Cited by 50 publications

(56 citation statements)

References 29 publications

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“…The rate of pathologic complete response (pCR) obtained with neoadjuvant chemotherapy has been only 2%-15% (9,10). Because targeted therapy and immunotherapy have shown excellent therapeutic promise in metastatic lung cancer, several studies have used them as neoadjuvant therapy for earlier-stage lung cancer (11)(12)(13). Unfortunately, phase 3 clinical trials have shown that neoadjuvant targeted therapy did not prolong overall survival: 9.7% of patients achieved major pathologic response (MPR), and no patients achieved pCR, although the progression-free survival benefit of neoadjuvant erlotinib was approximately 10 months longer than survival with neoadjuvant chemotherapy (14).…”

Section: Introductionmentioning

confidence: 99%

Surgical Outcomes After Neoadjuvant Chemoimmunotherapy for Resectable Non-Small Cell Lung Cancer

Ren

Wang

et al. 2021

Front. Oncol.

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BackgroundNeoadjuvant chemoimmunotherapy for resectable non-small cell lung cancer (NSCLC) represents an important research topic. Despite the potential benefits of this approach, the inflammatory responses and adverse events associated with neoadjuvant chemoimmunotherapy can present technical challenges and compromise a planned resection. This study assessed the safety and feasibility of neoadjuvant chemoimmunotherapy followed by surgery for resectable NSCLC.MethodsThe study was conducted from May 2019 to March 2021. Patients who were age 18 years or older, were diagnosed with stage Ib–IIIb NSCLC, and received neoadjuvant chemoimmunotherapy followed by surgery were included. Demographic information, clinical and pathologic characteristics, data about neoadjuvant therapy, and surgical details were collected by retrospective chart review. Toxicity profiles were collected retrospectively or by telephone follow-up.ResultsTwenty patients were included in this study. The median age was 56 years (range, 48–72 years), and 18 patients (90%) were men. Squamous carcinoma (14/20, 70%) was the most common cancer type, followed by adenocarcinoma (4/20, 20%), adenosquamous carcinoma (1/20, 5%), and large cell neuroendocrine carcinoma (1/20, 5%). All patients received two to four cycles of neoadjuvant therapy, and the median interval between final therapy and surgery was 49 days (range, 23–133 days). Computed tomography evaluation after neoadjuvant therapy showed partial response in 15 patients (75%) and stable disease in 5 (25%). Final pathologic examinations showed major pathologic response in eight patients, including pathologic complete response in five (25%). Most patients (18/20, 90%) had reduced pathologic staging. Twelve patients (60%) underwent open thoracotomy; the other eight patients underwent minimally invasive surgery, which was uneventful and without intraoperative conversion to open thoracotomy. No perioperative deaths occurred, and only seven patients (35%) developed postoperative complications. Most patients experienced only grade 1–2 adverse effects and laboratory abnormalities during neoadjuvant therapy, and no grade 3 or worse adverse effects or laboratory abnormalities occurred. No patients experienced surgical delays as a result of immune-related adverse events.ConclusionsPreoperative administration of chemoimmunotherapy for patients with resectable NSCLC was safe and feasible.

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Section: Introductionmentioning

confidence: 99%

Surgical Outcomes After Neoadjuvant Chemoimmunotherapy for Resectable Non-Small Cell Lung Cancer

Ren

Wang

et al. 2021

Front. Oncol.

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“…The most recent pooled analysis of 124 patients from five prospective clinical trials demonstrated a satisfactory surgical outcomes and good tolerability to use EGFR TKI in the neoadjuvant treatment of resectable NSCLC. 10 However, results in terms of objective response rate (ORR) and survival are inconsistent in many studies. 11 As the locally advanced NSCLCs are highly heterogeneous, a multidisciplinary team (MDT) involving oncologists, surgeons, pulmonologists and radiation oncologists is necessary to ensure a best practice of precision medicine.…”

Section: Discussionmentioning

confidence: 99%

Clinical and Pathologic Complete Response to Gefitinib in a Patient with SqCLC Harboring EGFR p.E746_S752delinsV Mutation

Zhuang¹,

Zhang²,

Tang³

et al. 2021

OTT

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Development of targeted therapies for squamous cell lung cancer (SqCLC) is currently limited by the prevalence of activating mutations and their predicting power of treatment efficacy. In the present study, we describe a case of treatment-naïve stage IIIB SqCLC that harbored a rare epidermal growth factor receptor (EGFR) p.E746_S752delinsV mutation with clinical complete response to neoadjuvant gefitinib. Pathological complete response was confirmed after surgical resection. No disease recurrence was documented after 20-month follow-up. This report suggested that first-generation EGFR tyrosine kinase inhibitor (TKI) could be an option in neoadjuvant context for advanced SqCLC patients harboring EGFR p.E746_S752delinsV mutation and highlighted the clinical benefits of EGFR testing in SqCLC patients who are females and never/former light smokers.

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“…A recent systematic review on neoadjuvant EGFR-TKI therapy for EGFR-mutant NSCLC concluded that this provides a feasible treatment modality with satisfactory surgical outcomes and low toxicity [ 49 ]. However, further phase III trials are necessary to confirm these findings.…”

Section: Neoadjuvant Immunotherapymentioning

confidence: 99%

Surgery after Induction Targeted Therapy and Immunotherapy for Lung Cancer

Allaeys

Berzenji

Schil

2021

Cancers

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Multimodality therapy for locally advanced non-small cell lung cancer (NSCLC) is a complex and controversial issue, especially regarding optimal treatment regimens for patients with ipsilateral positive mediastinal nodes (N2 disease). Many trials investigating neoadjuvant immunotherapy and targeted therapy in this subpopulation have shown promising results, although concerns have risen regarding surgical feasibility. A thorough literature review was performed, analyzing all recent studies regarding surgical morbidity and mortality. Despite the fact that two major trials investigating this subject were terminated early, the overall consensus is that surgical management seems feasible. However, dissection of hilar vessels may be challenging due to hilar fibrosis. Further research is necessary to identify the role of surgery in these multimodality treatment regimens, and to define matters such as the optimal treatment regimen, the dosage of the different agents used, the interval between induction therapy and surgery, and the role of adjuvant therapy.

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

Cited by 50 publications

References 29 publications

Surgical Outcomes After Neoadjuvant Chemoimmunotherapy for Resectable Non-Small Cell Lung Cancer

Surgical Outcomes After Neoadjuvant Chemoimmunotherapy for Resectable Non-Small Cell Lung Cancer

Clinical and Pathologic Complete Response to Gefitinib in a Patient with SqCLC Harboring EGFR p.E746_S752delinsV Mutation

Surgery after Induction Targeted Therapy and Immunotherapy for Lung Cancer

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