Thoracic: Lung CancerClinicopathologic outcomes of preoperative targeted therapy in patients with clinical stage I to III non–small cell lung cancer
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Section snippets
Patient Cohort
This study was approved by the institutional review board at Memorial Sloan Kettering Cancer Center, and all patients gave informed consent (MSK IRB 16-1395; approved August 26, 2016). We retrospectively reviewed data of patients with NSCLC who were treated from January 2004 to April 2021 with targeted therapy before surgical resection with curative intent. At the time of initial evaluation at our institution, all patients were planned to receive surgical resection after completion of their
Demographic Characteristics
In total, 51 patients met inclusion criteria, of whom 90% (46/51) had an EGFR alteration and 10% (5/51) had an ALK fusion. Of the overall cohort, 35 were women (35/51 [69%]), and 27 (27/51 [53%]) were never-smokers. The median age at surgery was 64 years (interquartile range, 55-72 years). Most patients (46/51 [90%]) underwent lobectomy, and all patients had an R0 resection. Surgical approach evolved over the course of the study, with most earlier patients having undergone open resection (27/51
Discussion
Targeted therapies are associated with longer survival among patients with advanced-stage NSCLC and when given as adjuvant therapy after complete surgical resection.8,12,16,18 In contrast, only a few studies, primarily in East Asian populations,35,36 have examined the use of TKIs in the neoadjuvant setting.20,21,37,38 Our study is, to our knowledge, the largest retrospective study, to date, to investigate preoperative TKI use in patients with activating EGFR mutations and ALK fusions. We found
Conclusions
Preoperative TKI targeted therapy was well tolerated in patients with clinical stage I to III NSCLC with actionable EGFR and ALK alterations (Figure 4). In addition, radiographic response strongly correlated with pathologic response, and preoperative targeted therapy, even when used alone, was associated with good RFS and OS.
References (53)
- et al.
Postoperative radiotherapy for surgically resected ypN2 non-small cell lung cancer
Ann Thorac Surg
(2018) - et al.
Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO clinical practice guidelines for diagnosis, treatment and follow-up
Ann Oncol
(2017) - et al.
Neoadjuvant chemotherapy and nivolumab in resectable non-small-cell lung cancer (NADIM): an open-label, multicentre, single-arm, phase 2 trial
Lancet Oncol
(2020) - et al.
Current status and future perspectives on neoadjuvant therapy in lung cancer
J Thorac Oncol
(2018) - et al.
Neoadjuvant crizotinib in resectable locally advanced non-small cell lung cancer with ALK rearrangement
J Thorac Oncol
(2019) - et al.
Memorial sloan kettering-integrated mutation profiling of actionable cancer targets (MSK-IMPACT): a hybridization capture-based next-generation sequencing clinical assay for solid tumor molecular oncology
J Mol Diagn
(2015) - et al.
Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors: guideline from the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology
J Thorac Oncol
(2018) - et al.
New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)
Eur J Cancer
(2009) - et al.
Pathological response after neoadjuvant chemotherapy in resectable non-small-cell lung cancers: proposal for the use of major pathological response as a surrogate endpoint
Lancet Oncol
(2014) - et al.
Multiple primary lung cancers
J Thorac Cardiovasc Surg
(1975)
Gefitinib plus chemotherapy versus placebo plus chemotherapy in EGFR-mutation-positive non-small-cell lung cancer after progression on first-line gefitinib (IMPRESS): a phase 3 randomised trial
Lancet Oncol
Intercalated combination of chemotherapy and erlotinib for patients with advanced stage non-small-cell lung cancer (FASTACT-2): a randomised, double-blind trial
Lancet Oncol
Survival outcome assessed according to tumor response and shrinkage pattern in patients with EGFR mutation-positive non-small-cell lung cancer treated with gefitinib or erlotinib
J Thorac Oncol
Preoperative chemotherapy in patients with resectable non-small cell lung cancer: results of the MRC LU22/NVALT 2/EORTC 08012 multicentre randomised trial and update of systematic review
Lancet
Factors associated with survival in complete pathologic response non-small cell lung cancer
Clin Lung Cancer
Histopathologic response criteria predict survival of patients with resected lung cancer after neoadjuvant chemotherapy
J Thorac Oncol
The magic of ADAURA?
J Thorac Oncol
Patterns of recurrence and second primary lung cancer in early-stage lung cancer survivors followed with routine computed tomography surveillance
J Thorac Cardiovasc Surg
Outcomes after neoadjuvant or adjuvant chemotherapy for cT2-4N0-1 non-small cell lung cancer: a propensity-matched analysis
J Thorac Cardiovasc Surg
Factors associated with distant recurrence following R0 lobectomy for pN0 lung adenocarcinoma
J Thorac Cardiovasc Surg
Targeted next-generation sequencing analysis for recurrence in early-stage lung adenocarcinoma
Ann Surg Oncol
Lung Adjuvant Cisplatin Evaluation: A Pooled Analysis by the LACE Collaborative Group. Database of Abstracts of Reviews of Effects (DARE): Quality-Assessed Reviews
NCCN guidelines insights: non-small cell lung cancer, version 1.2020
J Natl Compr Canc Netw
Preoperative chemotherapy for non-small-cell lung cancer: a systematic review and meta-analysis of individual participant data
Lancet
Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer
N Engl J Med
Evolution of systemic therapy for stages I-III non-metastatic non-small-cell lung cancer
Nat Rev Clin Oncol
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This work was supported by National Institutes of Health grants R01CA217169 and R01CA240472 (both to D.R.J.), National Institutes of Health grant R01CA236615 (to P.S.A.), Hamilton Family Foundation (to D.R.J.), Al-Asmakh Foundation (to D.R.J.), US Department of Defense grant LC160212 (to P.S.A.), and National Institutes of Health grant P30CA008748 (to Memorial Sloan Kettering Cancer Center).