The outcomes of a randomized phase II study in patients with platinum-treated, recurrent and/or metastatic squamous-cell carcinoma of the head and neck indicate that treatment with the PI3K inhibitor buparlisib plus paclitaxel provides an improved progression-free survival compared with paclitaxel alone (4.6 months versus 3.5 months). However, patients in the buparlisib group had a higher risk of grade 3–4 adverse events, including hyperglycaemia, anaemia and neutropenia — although investigators described the adverse event profile as manageable. These data provide evidence that buparlisib plus paclitaxel could be an effective approach in this setting, although data from phase III trials are required to support this hypothesis.