Pemetrexed in combination with cisplatin versus cisplatin monotherapy in patients with recurrent or metastatic head and neck cancer: Final results of a randomized, double-blind, placebo-controlled, phase 3 study

Susan Urba, Carla M L Van Herpen, Tarini Prasad Sahoo, Dong M. Shin, Lisa Licitra, Klara Mezei, Christoph Reuter, Ricardo Hitt, Francesca Russo, Shao Chun Chang, Anwar M. Hossain, Bente Frimodt-Moller, Andrew Koustenis, Ruey Long Hong

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) is associated with poor survival. Platinum-based chemotherapy is often a first-line treatment. Pemetrexed has shown single-agent activity in SCCHN and in combination with cisplatin for other tumors. This trial examined the efficacy of pemetrexed-cisplatin for SCCHN. METHODS: In a double-blind phase 3 trial, patients with recurrent or metastatic SCCHN and no prior systemic therapy for metastatic disease were randomized to pemetrexed (500 mg/m 2) plus cisplatin (75 mg/m2; n = 398) or placebo plus cisplatin (75 mg/m2; n = 397) to assess overall survival (OS) and secondary endpoints. RESULTS: Median OS was 7.3 months in the pemetrexed-cisplatin arm and 6.3 months in the placebo-cisplatin arm (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.75-1.02; P =.082). Median progression-free survival (PFS, months) was similar in both treatment arms (pemetrexed-cisplatin, 3.6; placebo-cisplatin, 2.8; HR, 0.88; 95% CI, 0.76-1.03; P =.166). Among patients with performance status 0 or 1, pemetrexed-cisplatin (n = 347) led to longer OS and PFS than placebo-cisplatin (n = 343; 8.4 vs 6.7 months; HR, 0.83; P =.026; 4.0 vs 3.0 months; HR, 0.84; P =.044, respectively). Among patients with oropharyngeal cancers, pemetrexed-cisplatin (n = 86) resulted in longer OS and PFS than placebo-cisplatin (n = 106; 9.9 vs 6.1 months; HR, 0.59; P =.002; 4.0 vs 3.4 months; HR, 0.73; P =.047, respectively). Pemetrexed-cisplatin toxicity was consistent with studies in other tumors. CONCLUSIONS: Pemetrexed-cisplatin compared with placebo-cisplatin did not significantly improve survival for the intent-To-Treat population. However, in a prespecified subgroup analysis, pemetrexed-cisplatin showed OS and PFS advantage for patients with performance status 0 or 1 or oropharyngeal cancers.

Original languageEnglish
Pages (from-to)4694-4705
Number of pages12
JournalCancer
Volume118
Issue number19
DOIs
Publication statusPublished - Oct 1 2012

Keywords

  • cisplatin
  • clinical trial
  • head and neck cancer
  • pemetrexed
  • phase 3

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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