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)

Ann Oncol. 2015 Sep;26(9):1877-1883. doi: 10.1093/annonc/mdv276. Epub 2015 Jul 3.


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.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carboplatin / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / therapeutic use
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics
  • Erlotinib Hydrochloride / therapeutic use*
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / mortality
  • Male
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use
  • Survival Analysis
  • Treatment Outcome


  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Deoxycytidine
  • gemcitabine
  • Carboplatin
  • Erlotinib Hydrochloride
  • EGFR protein, human
  • ErbB Receptors

Associated data