Addition of pemetrexed to cisplatin did not boost survival in head and neck cancers

This large phase 3 randomized trial compared cisplatin monotherapy for up to six cycles to cisplatin in combination with pemetrexed for up to six cycles, demonstrating no significant improvement in OS for the combination in unselected patients. Although a substantial minority of patients received at least one regimen of post-study therapy, there was no meaningful difference in PFS. Response rates were low in each arm, and there was a slight excess of deaths on treatment or potentially related to the study drug on the combination arm. These findings are compatible with studies from the pre-cetuximab era, which also failed to conclusively demonstrate that doublet chemotherapy was superior to cisplatin monotherapy. The researchers undertook several pre-planned subset analyses. They demonstrated a benefit for doublet therapy in patients with performance status 0 or 1, when compared with those with performance status 2. Even among the performance status 0 or 1 patients, the response rate, PFS and OS did not equal those for doublet chemotherapy plus cetuximab. The researchers also demonstrated a benefit for doublet therapy in patients with oropharynx cancer. It is likely that this group included some patients with HPV-associated cancer, who may have been younger and healthier; however, no HPV polymerase chain reaction or p16 immunohistochemical data were derived to assess what proportion of the patients had HPV-associated disease. Thus, the cisplatin/pemetrexed combination will have a limited role in the management of head and neck cancers at present. Future studies, which identify more specific biomarkers of pemetrexed response, would be warranted only in good performance status patients.