Final efficacy outcomes of atezolizumab with chemoradiation for unresectable NSCLC: The phase II DETERRED trial

Lung Cancer. 2022 Dec:174:112-117. doi: 10.1016/j.lungcan.2022.10.006. Epub 2022 Oct 29.

Abstract

Introduction: The phase II DETERRED trial assessed the safety and efficacy of consolidation and concurrent immunotherapy with chemoradiation in unresectable locally advanced non-small cell lung cancer. We present updated efficacy analysis of this trial.

Methods: The trial was conducted in 2 parts with patients in part 1 (n = 10) receiving chemoradiation with consolidation atezolizumab, while patients in part 2 (n = 30) received concurrent and consolidation atezolizumab. Progression-free survival (PFS), time to second progression (PFS2), and overall survival (OS) were assessed using Kaplan-Meier analysis. Subset analyses were performed by programmed cell death ligand-1 (PD-L1) status and targetable driver oncogene mutation status.

Results: At a median follow-up of 39.2 months, the median PFS for part 1 was 18.9 months and 15.1 months for part 2. Median OS for part 1 was 26.5 months and was not reached for part 2. For the cohort, 3-year OS was 53.8%, while 4-year OS was 47.4%. Patients with targetable driver oncogene mutations had a median PFS of 9.4 months and OS of not reached compared to 16.6 months (HR: 3.49, p = 0.02) and 26.9 months (HR: 0.40, p = 0.12) respectively compared to those without targetable driver oncogene mutations. Patients with PD-L1 < 1% had median PFS of 11.0 months and OS of 26.5 months compared to 27.4 months (HR: 2.01, p = 0.10) and not reached (HR: 1.49, p = 0.41) respectively for those with PD-L1 ≥ 1%.

Conclusions: In the DETERRED trial, chemoradiation with concurrent and/or consolidative atezolizumab led to comparable efficacy as consolidative durvalumab in the PACIFIC trial. The presence of targetable driver oncogene mutations led to worse PFS, while PD-L1 < 1% trended to worse PFS.

Keywords: Atezolizumab; Driver mutations; Immunotherapy; Non-small cell lung cancer; Radiation; Targeted therapy.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / metabolism
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / therapy
  • Chemoradiotherapy
  • Humans
  • Immunotherapy
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics

Substances

  • B7-H1 Antigen