Head and neck squamous cell carcinoma (HNSCC) mortality is ~40%, despite the fact that only ~5% of patients have metastatic disease at presentation. Hence, improved treatments are needed, particularly for those with locally advanced disease (LA-HNSCC), with new data indicating the promise of risk-stratified induction therapy.

In a phase II trial, patients with LA-HNSCC of the oropharynx, oral cavity, nasopharynx, hypopharynx or larynx (T0–4N2b–2c/3M0) received either paclitaxel, carboplatin and the anti-EGFR antibody cetuximab (PCC) or cetuximab, docetaxel, cisplatin and 5-fluorouracil (C-TPF) before local treatment. The 68 patients in each group were stratified into low-risk or higher-risk subgroups according to human papillomavirus (HPV) status and T stage.

Overall, 2-year progression-free survival (PFS) was similar between the treatment arms and, with C-TPF, between the risk groups (88–89% in each comparison). By contrast, 2-year PFS with PCC was greater in patients with low-risk disease than in those with higher-risk disease (96% versus 67%). Thus, PCC and C-TPF might be the preferable induction therapies for low-risk (HPV+ T0–3 or HPV T0–2) and higher-risk (HPV+ T4 or HPV T3–4) disease, respectively. Notably, in comparison with historical cohorts from the RTOG-0129 trial of concurrent chemoradiotherapy without induction therapy, 2-year PFS was improved by >20% with PCC in the low-risk group and with C-TPF in the higher-risk group.

In general, PCC and C-TPF had similar safety profiles; although, statistically significant differences in the rates of grade 3–4 skin rash (35% versus 3%), nausea (9% versus 25%), hypomagnesaemia (1.5% versus 7.4%) and neutropenia (22% versus 30%) were observed.

Further research is needed to establish the optimal approach to risk-stratified induction therapy. More importantly, the true value of induction therapy for LA-HNSCC remains controversial and needs to be clarified.