Expression of matrix metalloproteinases 1, 2, 9 and their tissue inhibitors in stage II non-small cell lung cancer: Implications for MMP inhibition therapy

8501 Background: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor is a standard of care for EGFR mutation-positive, untreated metastatic non-small cell lung cancer (NSCLC). However, the efficacy and safety of adjuvant gefitinib for patients with completely resected lung cancer harboring EGFR mutation over cisplatin-based adjuvant chemotherapy were not known in 2011 when this study was initiated. Methods: From September 2011 to December 2015, we randomly assigned 234 patients with completely resected, EGFR mutation-positive (exon 19 deletion or L858R), stage II–III NSCLC to receive either gefitinib (250 mg, once daily) for 24 months or cisplatin (80 mg/m2 on day 1) plus vinorelbine (25 mg/m2 on days 1 and 8) (cis/vin) every 3 weeks for four cycles. The primary endpoint was disease-free survival (DFS) according to a central review in the intent-to-treat (ITT) population. Results: Two patients in the gefitinib arm withdrew consent and were excluded from the ITT population. No treatment-related deaths were seen in the gefitinib arm, but three treatment-related deaths were reported in the cis/vin arm. Median duration of follow-up was 71 months. Median DFS was numerically longer in the gefitinib arm (36 months) than in the cis/vin arm (25.2 months). However, Kaplan-Meier curves began to overlap around 5 years after surgery, and no significant difference in DFS was seen, with a hazard ratio (HR) of 0.92 (95% confidence interval (CI), 0.67–1.28; P = 0.63). Overall survival was also not significantly different (median not reached in either arm). Five-year survival rates for gefitinib and cis/vin arms were 78.0% and 74.6%, respectively, with an HR for death of 1.03; 95%CI, 0.65–1.65; P = 0.89. Exploratory subset analysis revealed that patients ³70 years old in the gefitinib arm (n = 19/27 with G to cis/vin) survived longer than those in the cis/vin arm (HR 0.31; 95%CI, 0.10–0.98; P = 0.046). Conclusions: Adjuvant gefitinib appeared to prevent early relapse, but did not significantly prolong DFS or OS in patients with completely resected stage II–III, EGFR-mutated NSCLC. The apparent non-inferiority of DFS/OS may justify the use of adjuvant gefitinib in selected subset of patients, especially those deemed unsuitable for cis/vin adjuvant therapy. Clinical trial information: UMIN000006252.

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P3.16-006 Impact of Limited Resection or Omitted Adjuvant Therapy in Patients with Pathologic Stage II and III Non-Small-Cell Lung Cancer

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2017.09.1812 ◽

2017 ◽

Vol 12 (11) ◽

pp. S2345

Author(s):

J.S. Cho ◽

Y.D. Kim ◽

H.Y. Ahn ◽

H. I ◽

J. Son

Keyword(s):

Lung Cancer ◽

Adjuvant Therapy ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Limited Resection ◽

Stage Ii ◽

Small Cell Lung ◽

Pathologic Stage

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Postoperative Radiation Therapy Is Associated With Improved Overall Survival in Incompletely Resected Stage II and III Non–Small-Cell Lung Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2015.61.1517 ◽

2015 ◽

Vol 33 (25) ◽

pp. 2727-2734 ◽

Cited By ~ 45

Author(s):

Elyn H. Wang ◽

Christopher D. Corso ◽

Charles E. Rutter ◽

Henry S. Park ◽

Aileen B. Chen ◽

...

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Patient Population ◽

Small Cell ◽

Stage Ii ◽

Small Cell Lung ◽

Nodal Stage ◽

Resected Stage

Purpose To review trends in the use of postoperative radiotherapy (PORT) for stage II and III incompletely resected non–small-cell lung cancer (NSCLC) and evaluate the association between PORT and survival in such patients. Patients and Methods We identified patients with pathologic stage N0-2, overall American Joint Committee on Cancer stage II or III NSCLC within the National Cancer Data Base who had undergone a lobectomy or pneumonectomy with positive surgical margins. Only patients coded as receiving external-beam PORT at 50 to 74 Gy or observation were included. To account for perioperative mortality, we excluded patients who survived less than 4 months after diagnosis. Multivariable logistic regression was used to determine factors associated with PORT receipt. Cox proportional hazards regression was performed for multivariable analyses of overall survival. Results Among 3,395 included patients, 1,207 (35.6%) received PORT. Predictors for the use of PORT among this patient population included age less than 60 years, treatment in a nonacademic facility, earlier year of diagnosis, decreased travel distance, lower nodal stage, and chemotherapy receipt. On multivariable analysis adjusting for demographic and clinicopathologic covariates, PORT (hazard ratio, 0.80; 95% CI, 0.70 to 092) was associated with improved survival. Subset analysis by nodal stage showed that PORT improved survival across all nodal stages. Conclusion PORT is associated with improved overall survival in patients with incompletely resected stage II or III N0-2 NSCLC. The use of PORT for this population in more recent years has been declining. In the absence of randomized trials evaluating PORT utilization for this patient population, our findings strongly support the delivery of PORT in patients with incompletely resected NSCLC.

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