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.
Author(s): Urba S, van Herpen CM, Sahoo TP, Shin DM, Licitra L, Mezei K, Reuter C, Hitt R,
Russo F, Chang SC, Hossain AM, Frimodt-Moller B, Koustenis A, Hong RL.
Affiliation(s): Division of Hematology/Oncology, University of Michigan Comprehensive Cancer
Center, Ann Arbor, Michigan, USA. surba@umich.edu
Publication date & source: 2012, Cancer. , 118(19):4694-705
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 = 398) or placebo plus
cisplatin (75 mg/m(2) ; 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.
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