Necitumumab plus Gemcitabine and Cisplatin as First-Line Therapy in Patients with Stage IV EGFR- Expressing Squamous Non-Small-Cell Lung Cancer: German Subgroup Data from an Open-Label, Randomized Controlled Phase 3 Study (SQUIRE)

Oncol Res Treat. 2016;39(9):539-47. doi: 10.1159/000448085. Epub 2016 Aug 2.

Abstract

Background: In the SQUIRE study, adding the anti-epidermal growth factor receptor (EGFR) IgG1 antibody necitumumab to first-line gemcitabine and cisplatin (GC + N) in advanced squamous non-small-cell lung cancer (sqNSCLC) significantly improved overall survival (OS); the safety profile was acceptable. We explored data for the German subpopulation (N = 96) of SQUIRE patients with EGFR-expressing tumors.

Patient and methods: Patients with stage IV sqNSCLC were randomized 1:1 to up to 6 cycles of open-label GC + N or GC alone. GC + N patients with no progression continued on necitumumab monotherapy until disease progression or intolerable toxicity. The primary endpoint was OS; the secondary endpoints included progression-free survival (PFS), safety and health-related quality of life (EQ-5D, Lung Cancer Symptom Scale (LCSS)).

Results: The 96 German SQUIRE patients with EGFR-expressing tumors (GC + N 42, GC 54) received a median of 4 GC cycles; the GC + N patients received 5 cycles of necitumumab. Adding necitumumab was associated with 41% risk reduction of death (hazard ratio (HR) 0.59, 95% confidence interval (CI) 0.37-0.94, p = 0.026) and 44% risk reduction of progression (HR 0.56, 95% CI 0.33-0.95, p = 0.029). Adverse events typically associated with EGFR antibody treatment (including rash, hypomagnesemia) were more common with GC + N. The time to deterioration of the EQ-5D and LCSS scores showed no notable differences between the treatment arms, except for appetite loss (delayed for GC + N).

Conclusion: The survival benefit from adding necitumumab to first-line GC was more pronounced in the German SQUIRE subpopulation with EGFR-expressing tumors than in the overall (intention-to-treat) population; toxicity was manageable and consistent with the overall population.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cisplatin / administration & dosage
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • ErbB Receptors / metabolism
  • Female
  • Gemcitabine
  • Germany / epidemiology
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prevalence
  • Risk Factors
  • Survival Rate
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Deoxycytidine
  • necitumumab
  • EGFR protein, human
  • ErbB Receptors
  • Cisplatin
  • Gemcitabine