Long-term survival in patients with advanced non-small-cell lung cancer treated with atezolizumab versus docetaxel: Results from the randomised phase III OAK study

Eur J Cancer. 2019 Jan:107:124-132. doi: 10.1016/j.ejca.2018.11.020. Epub 2018 Dec 17.

Abstract

Background: Atezolizumab (anti-programmed death-ligand 1 [PD-L1]) received approval from the US Food and Drug Administration and European Medicines Agency for previously treated advanced non-small-cell lung cancer based on OAK-a randomised, phase III trial that showed significantly improved survival with atezolizumab versus docetaxel regardless of PD-L1 expression. With longer follow-up, we summarised the characteristics of long-term survivors (LTSs).

Methods: In OAK (NCT02008227), patients were randomised 1:1 to receive atezolizumab or docetaxel until loss of clinical benefit or disease progression, respectively. Overall survival was evaluated after a 26-month minimum follow-up, including in patient subgroups defined by best overall response (BOR). LTSs were defined as patients who lived ≥24 months since randomisation. Non-LTSs died within 24 months, and patients censored before 24 months were excluded from the analysis. The baseline characteristics, including biomarkers, BOR, subsequent non-protocol therapy (NPT) and safety, are reported.

Results: Survival benefit with atezolizumab was observed across all patient subgroups defined by BOR. More atezolizumab-treated patients were LTSs versus those treated with docetaxel (28% versus 18%). Most atezolizumab responders were LTSs (77%) versus only 48% of docetaxel responders. However, 21% of atezolizumab-arm LTSs had progressive disease (PD) as BOR, and more atezolizumab-arm LTSs than non-LTSs continued treatment post-PD. Fifty-two percent of docetaxel-arm LTSs received immunotherapy as subsequent NPT. Despite extended treatment duration in atezolizumab-arm LTSs (median, 18 months), atezolizumab was well tolerated.

Conclusions: After >2 years of follow-up, atezolizumab continued to provide durable survival benefit versus docetaxel, with tolerable safety. Atezolizumab-arm LTSs were enriched for patients with high PD-L1 expression and included PD-L1-negative patients. Long-term survival was not limited to responders.

Keywords: Atezolizumab; Cancer immunotherapy; Long-term survival; PD-L1; Second-line NSCLC.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / analysis
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / mortality*
  • Carcinoma, Squamous Cell / pathology
  • Docetaxel / administration & dosage
  • Female
  • Follow-Up Studies
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Prognosis
  • Survival Rate
  • Survivors / statistics & numerical data*

Substances

  • Antibodies, Monoclonal, Humanized
  • Biomarkers, Tumor
  • Docetaxel
  • atezolizumab