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.
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Original article
Haddad, R. I. et al. Weekly paclitaxel, carboplatin, cetuximab, and cetuximab, docetaxel, cisplatin, and fluorouracil, followed by local therapy in previously untreated, locally advanced head and neck squamous cell carcinoma. Ann. Oncol. https://doi.org/10.1093/annonc/mdy549 (2018)
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Killock, D. Towards risk-stratified induction regimens. Nat Rev Clin Oncol 16, 209 (2019). https://doi.org/10.1038/s41571-019-0168-6
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DOI: https://doi.org/10.1038/s41571-019-0168-6