Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802)
C Zhou, Y L Wu, G Chen, J Feng, X-Q Liu, C Wang, S Zhang, J Wang, S Zhou, S Ren, S Lu, L Zhang, C Hu, C Hu, Y Luo, L Chen, M Ye, J Huang, X Zhi, Y Zhang, Q Xiu, J Ma, L Zhang, C You, C Zhou, Y L Wu, G Chen, J Feng, X-Q Liu, C Wang, S Zhang, J Wang, S Zhou, S Ren, S Lu, L Zhang, C Hu, C Hu, Y Luo, L Chen, M Ye, J Huang, X Zhi, Y Zhang, Q Xiu, J Ma, L Zhang, C You
Abstract
Background: The OPTIMAL study was the first study to compare efficacy and tolerability of the epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) erlotinib, versus standard chemotherapy in first-line treatment of patients with EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). Findings from final overall survival (OS) analysis and assessment of post-study treatment impact are presented.
Patients and methods: Of 165 randomised patients, 82 received erlotinib and 72 gemcitabine plus carboplatin. Final OS analyses were conducted when 70% of deaths had occurred in the intent-to-treat population. Subgroup OS was analysed by Cox proportional hazards model and included randomisation stratification factors and post-study treatments.
Results: Median OS was similar between the erlotinib (22.8 months) and chemotherapy (27.2 months) arms with no significant between-group differences in the overall population [hazard ratio (HR), 1.19; 95% confidence interval (CI) 0.83-1.71; P = 0.2663], the exon 19 deletion subpopulation (HR, 1.52; 95% CI 0.91-2.52; P = 0.1037) or the exon 21 L858 mutation subpopulation (HR, 0.92; 95% CI 0.55-1.54; P = 0.7392). More patients in the erlotinib arm versus the chemotherapy arm did not receive any post-study treatment (36.6% versus 22.2%). Patients who received sequential combination of EGFR-TKI and chemotherapy had significantly improved OS compared with those who received EGFR-TKI or chemotherapy only (29.7 versus 20.7 or 11.2 months, respectively; P < 0.0001). OS was significantly shorter in patients who did not receive post-study treatments compared with those who received subsequent treatments in both arms.
Conclusion: The significant OS benefit observed in patients treated with EGFR-TKI emphasises its contribution to improving survival of EGFR mutant NSCLC patients, suggesting that erlotinib should be considered standard first-line treatment of EGFR mutant patients and EGFR-TKI treatment following first-line therapy also brings significant benefits to those patients.
Clinicaltrialsgov identifier: NCT00874419.
Keywords: EGFR mutations; chemotherapy; erlotinib; non-small-cell lung cancer; overall survival.
© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Source: PubMed