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

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/m 2 ;n ¼ 398) or placebo plus cisplatin (75 mg/m 2 ;n ¼ 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 placebocisplatin arm (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.75-1.02; P ¼ .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 ¼ .166). Among patients with performance status 0 or 1, pemetrexed-cisplatin (n ¼ 347) led to longer OS and PFS than placebo-cisplatin (n ¼ 343; 8.4 vs 6.7 months; HR, 0.83; P ¼ .026; 4.0 vs 3.0 months; HR, 0.84; P ¼ .044, respectively). Among patients with oropharyngeal cancers, pemetrexed-cisplatin (n ¼ 86) resulted in longer OS and PFS than placebo-cisplatin (n ¼ 106; 9.9 vs 6.1 months; HR, 0.59; P ¼ .002; 4.0 vs 3.4 months; HR, 0.73; P ¼ .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 intentto-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. Cancer 2012;118:4694-705. V C 2012 American Cancer Society.