Lung Cancer

SS 04 - Lung 2 - Stage III/IV

31 - Cyclooxygenase-2 Genetic Variants Are Predictive of Patient Benefit:Biomarker Analyses From a Randomized Phase II Trial Evaluating Concurrent Chemoradiotherapy With or Without Celecoxib in Unresectable Stage III Non-Small Cell Lung Cancer

Sunday, October 21
4:55 PM - 5:05 PM
Location: Room 301

Cyclooxygenase-2 Genetic Variants Are Predictive of Patient Benefit:Biomarker Analyses From a Randomized Phase II Trial Evaluating Concurrent Chemoradiotherapy With or Without Celecoxib in Unresectable Stage III Non-Small Cell Lung Cancer
N. Bi1, J. Liang1, Z. Zhou1, D. Chen2, Z. Fu3, X. Yang2, Z. Hui1, Q. Feng1, Z. Xiao2, J. Lv4, X. Wang4, T. Zhang4, X. Wang5, L. Deng2, W. Wang6, J. Wang7, J. Ran8, and L. Wang1; 1Department of Radiation Oncology, National Cancer Center / Cancer Institute & Hospital, Chinese Academic of Medical Sciences, Peking Union Medical College, Beijing, China, 2Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, 3Chinese Academy of Medical Sciences and Peking Union Medical College,Cancer Hospital, Beijing, China, 4National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, 5Department of Radiation Oncology, National Cancer Center, Cancer Hospital/Institute, Chinese Acedemy of Medical Sciences & Peking Union Medical College, Bejing, China, 6Department of Radiation Oncology, National Cancer Center / Cancer Institute & Hospital, Chinese Academic of Medical Sciences, Beijing, China, 7National Cancer Center / Cancer Institute & Hospital, Chinese Academic of Medical Sciences, Peking Union Medical College, Beijing, China, 8Department of Radiation Oncology, National Cancer Center/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

Purpose/Objective(s): Cyclooxygenase-2 (COX-2) plays important roles in the modulation of apoptosis, angiogenesis, immune response, and tumor invasion. A COX-2 single-nucleotide polymorphisms (SNP),−1195G/A (rs689466), is a potential prognostic marker in locally advanced non-small cell lung cancer (NSCLC) treated with chemoradiation (CRT). COX-2 −1195AA genotype (high-risk) might be more aggressive and probably more radiation resistant than those with the −1195GA +GG (low-risk) genotypes. The goal of the present study was to test the hypothesis that patients with the high-risk genotype benefit the most from COX-2 blockade.

Materials/Methods: This was an open-label randomized phase II trial. Patients with unresectable stage III NSCLC confirmed cytologically or histologically were eligible, and were randomly received 60Gy of thoracic radiation therapy concurrent with etoposide 50mg/m2 on days 1–5 and cisplatin 50mg/m2 on days 1 and 8 every 4 weeks for two cycles alone (control arm), or the same regimen of CRT combined with celecoxib, a COX-2 inhibitor (celecoxib arm). Celecoxib 200mg twice daily was started one week before initiation of radiation therapy and was continued without interruption until the end of radiation therapy. A prospectively planned genotyping of COX-2 −1195G/A SNP from blood lymphocytes were analyzed using mass spectrometry. This study is registered with ClinicalTrials. gov (NCT01503385)

Results: Between 2011 and 2015, out of 100 patients who were initially recruited, 96 (96%) were eligible and 90 (90%) completed treatment as planned. There were no significant baseline differences between two arms. With a median follow-up time of 50 months, the overall survival (OS) was similar for patients who received celecoxib as compared to those who did not (MST, 32.5 months versus 34.4 months; P=0. 833). Celecoxib concurrent with CRT was tolerated well and the risk of severe toxicity (≥G3) were comparable (P=0.471). 63 patients (70%) displayed genotyping. 19 (30.2%) were high-risk genotypes (9 in the control arm and 10 in the celecoxib arm). Genotype was not prognostic for OS or progression-free survival (PFS) in the control arm, but was for both OS (HR 0.62, 95% CI 0.36-1.07, P=0.076) and PFS (HR 0.58, 95% CI 0.36-0.93, P=0.017) in the celecoxib arm. In patients with high-risk genotypes, celecoxib was associated with higher PFS (HR 0.36, 95% CI 0.13-1.04, P=0.050) and trends of higher OS (HR 0.50, 95% CI 0.15-1.72, P=0.263) than was control treatment, but not in patients who had low-risk genotype. Additionally, the predictive role of the COX-2 genotype is independent of EGFR mutations.

Conclusion: The COX-2 high risk subtype can identify patients with unresectable stage III NSCLC who are likely to benefit from CRT combined with celecoxib therapies.

Author Disclosure: N. Bi: None. J. Liang: None. Z. Zhou: None. Z. Hui: None.

Nan Bi, MD, PhD

Disclosure:
Employment
ational Cancer Center / Cancer Institute & Hospital: Employee: Employee

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31 - Cyclooxygenase-2 Genetic Variants Are Predictive of Patient Benefit:Biomarker Analyses From a Randomized Phase II Trial Evaluating Concurrent Chemoradiotherapy With or Without Celecoxib in Unresectable Stage III Non-Small Cell Lung Cancer

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