Hat trick.

Top Line: Is concurrent cetuximab comparable to weekly cisplatin for patients receiving definitive radiation for head and neck squamous cell carcinoma (HNSCC)?

The Study: RTOG 1016 and De-ESCALaTE HPV were both randomized trials of concurrent chemoradiation with cisplatin or cetuximab for locally advanced, HPV-positive HNSCC. Both showed worse disease control and overall survival with cetuximab. ARTSCAN III was a similar Swedish trial of nearly 300 patients with locoregionally advanced HNSCC. In contrast to 1016 and De-ESCALaTE, sites outside the oropharynx were included and p16-positivity was not required. However, 85% of patients still had oropharyngeal primaries and 89% of those were p16-positive. They received either weekly cisplatin or weekly cetuximab, and there was a second randomization for T3/4 tumors to 68 Gy @ 2 Gy per fraction vs 73.1 Gy @ 2.15 Gy per fraction to the primary tumor. On interim analysis, the trial was terminated early due to an apparent increase in local recurrence events with cetuximab. At 3 years, the cumulative incidence of locoregional failure was more than doubled with cetuximab (9→ 23%). Overall survival at 3 years was 88% with cisplatin versus 78% with cetuximab. This is similar to the 5-year OS results of RTOG 1016, but they did not reach significance in this trial. With respect to the RT dose randomization, there was no difference in local control. Once again, cetuximab had a different toxicity profile, but it did not reduce the overall toxicity rate. 

TBL: Concurrent cetuximab results in inferior locoregional control compared to weekly cisplatin for HNSCC. | Gebre-Medhin, J Clin Oncol 2020

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