When would you use concurrent cetuximab with radiation for a patient with H&N cancer who is not a good candidate for concurrent chemotherapy?

Additional data has been added since I have addressed this question in 2015: the role of concurrent cet-RT in HNC patients who cannot receive chemotherapy. The large majority of these patients are elderly with heavy smoking/drinking history, and typically have non-HPV related Sqcca associated with poor prognosis.

An analysis of a subset of the patients randomized to RT vs cetuximab RT suggested that adding cet to RT resulted in improved outcomes for OPC pts with either HPV- and HPV+, compared with RT alone (Rosenthal DL et al, JCO 2016). Retrospective data from MSK and Stanford suggested that HNC patients treated with cet-RT faired poorly compared with those receiving chemo-RT; however, the patients in these studies who received cet-RT were older and had higher morbidity rates compared with those receiving chemo-RT, and likely had predominantly HPV- tumors (Shapiro LQ, Oral Onc 2014; Tang C, Head Neck 2015). Similar poor results were observed in our prospective study of cetuximab-RT in OPC patients who could not receive chemo-RT, most of whom were HPV- [Swiecciki P et al, JCO 34 (15 Suppl) 6017, 2016]. The recent results of RTOG 1016, which included only HPV+ OPC patients, clarified the effects of cet-RT vs chemo-RT without the confounding selecting factors inherent in the previous studies. The better tumor outcome and, surprisingly, the lower sequellae, in the chemo-RT compared with the cet-RT arm makes the choice of cet-RT for future patients questionable. The alternatives are treating with concurrent non-nephrotoxic chemotherapy and, importantly, implementing early interventions to manage toxicities and symptoms, preferably using a dedicated NP (Mason H et al, Oncol Nurs Forum 2013). In our experience these measures enabled treating successfully patients who otherwise would be regarded ineligible for chemotherapy.

The characteristics of oropharyngeal cancers that are HPV-related are low EGFR expression. I thought that HPV-related cancers in heavy smokers would show higher EGFR expression than in non-smokers, explaining the somewhat lower outcome of smokers. However, our study found that all HPV(+) opc patients had low expression of EGFR, while all HPV(-) had EGFR overexpression (these results are published in Vainshtein JM et al, Oral Oncology 2014;50:513-9). A recent abstract (Rosenthal DI, JCO 2014; 32:5s, suppl., abstract 6001) found that cetuximab was effective in the Bonner study in both HPV(+) and (-). However, there was no stratification for HPV in the original study, and HPV(+) with low EGFR were expected to do better regardless of cetuximab.

I would recommend cetuximab only in OPC: there is no evidence whatsoever that it is effective in other sites. Moreover, in an elderly patient with advanced cancer who cannot tolerate concurrent chemo I prefer altered fractionated RT over concurrent cetuximab: there are many randomized studies showing the benefit of altered fractionation vs standard radiation (without chemo), while for concurrent cetuximab that is thus far only one randomized study.