Prognostic Variables Associated With Improved Outcomes in Patients With Stage III NSCLC Treated With Chemoradiation Followed by Consolidation Pembrolizumab: A Subset Analysis of a Phase II Study From the Hoosier Cancer Research Network LUN 14-179

Clin Lung Cancer. 2020 May;21(3):288-293. doi: 10.1016/j.cllc.2019.06.009. Epub 2019 Jul 8.

Abstract

Introduction: The Hoosier Cancer Research Network (HCRN) LUN 14-179 is a phase II trial of consolidation pembrolizumab after concurrent chemoradiation for the treatment of patients with stage III non-small-cell lung cancer (NSCLC). Time to metastatic disease or death (TMDD), progression-free survival (PFS), and overall survival (OS) appear to be superior to that in historical controls of chemoradiation alone. Unfortunately, not all patients benefit from consolidation immunotherapy. We performed a univariate analysis to evaluate variables associated with PFS, metastatic disease, and OS.

Patients and methods: We conducted a retrospective analysis of patients enrolled in HCRN LUN 14-179. Data collected included age, sex, stage, smoking status, programmed death ligand 1 status, Grade (G) ≥ 2 versus G ≤ 1 adverse event, G ≤ 2 versus G ≥ 3 pneumonitis, duration of pembrolizumab (< 4 vs. ≥ 4 cycles), chemotherapy regimen, performance status 0 versus 1, time to start pembrolizumab (4-6 vs. 6-8 weeks from radiation), volume of lung receiving at least 20 Gy of radiation (V20; < 20% vs. ≥ 20%). Univariable Cox regression was performed to determine the variables associated with 3 end points: TMDD, PFS, and OS.

Results: From April 2015 to December 2016, 93 patients were enrolled and 92 were included in the efficacy analysis (1 patient was ineligible). For TMDD, improved outcomes might be associated (P < .1) with stage IIIA and ≥ 4 cycles of pembrolizumab. For PFS, improved outcomes (P < .1) might be seen for ≥ 4 cycles of pembrolizumab, stage IIIA and V20 < 20%. For OS, improved outcomes (P < .1) might be seen for stage IIIA and ≥ 4 cycles of pembrolizumab.

Conclusion: Stage IIIA and longer duration of pembrolizumab treatment might be associated with prolonged TMDD, PFS, and OS for patients with stage III NSCLC treated with chemoradiation followed by pembrolizumab.

Keywords: Adjuvant therapy; Consolidation; Immunotherapy; Non–small-cell lung cancer; Prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • 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
  • Chemoradiotherapy / mortality*
  • Cisplatin / administration & dosage
  • Clinical Trials, Phase II as Topic / statistics & numerical data*
  • Consolidation Chemotherapy / mortality*
  • Etoposide / administration & dosage
  • Female
  • Follow-Up Studies
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / pathology
  • Male
  • Paclitaxel / administration & dosage
  • Pemetrexed / administration & dosage
  • Prognosis
  • Retrospective Studies
  • Survival Rate

Substances

  • Antibodies, Monoclonal, Humanized
  • Pemetrexed
  • Etoposide
  • pembrolizumab
  • Paclitaxel
  • Cisplatin