A retrospective cohort study evaluating cetuximab super-responders with recurrent or metastatic squamous cell carcinoma of the head and neck.

Abstract

e18009 Background: Cetuximab is a key targeted therapy in squamous cell carcinoma of the head and neck (SCCHN), supported by near-universal EGFR overexpression. Early studies established its use with platinum-based chemotherapy and as post-platinum monotherapy, though outcomes remain modest: in platinum-refractory disease, response rates are ~13% with median progression of 2–3 months. Since the advent of immune checkpoint inhibitors, cetuximab is primarily used in later-line or combination settings. Despite limited efficacy, rare exceptional responses lasting 12 months to over 5 years have been reported. Here, we evaluated 13 patients across two academic health systems—the largest series reported to date—to identify features associated with durable benefit. Methods: We conducted a retrospective observational study of relapsed/metastatic SCCHN patients treated with cetuximab for ≥6 months at two academic centers (VCU and FHCC). Thirteen patients were identified through IRB-approved informatics queries and underwent detailed chart review. Treatment duration ≥6 months was defined as durable benefit. Results: Dates of diagnosis ranged from April 15, 2009, to June 7, 2022, with a median disease-free survival of 9.5 months. First-line R/M therapy yielded an ORR of 46.2%, increasing to 71.4% among patients treated with cetuximab plus chemotherapy. Four patients achieved radiographic complete responses, three with cetuximab-based combinations. Median PFS was 7 months and median OS was 35 months, with 69.2% alive at 12 months. Nine patients received second-line therapy, with an ORR of 22% and median PFS of 6 months. Conclusions: Sustained disease control beyond 6 months with cetuximab is uncommon, as historical trials report median treatment durations of 4–5 months. In this multi-institutional series, a subset of patients demonstrated exceptionally durable responses that exceeded historical expectations. Limited benefit from prior therapies argues against indolent disease biology, while deep and durable responses to platinum–cetuximab combinations suggest a biologically distinct subgroup. These findings support further investigation using integrated molecular and tumor microenvironment profiling to better define cetuximab “super-responders.” Line Patients (n) Therapy ORR CR Median PFS (months, 95% CI) Progressions Median OS (months, 95% CI) 1-yr OS (95% CI) First-line 13 Any therapy 46.2% (6/13) 4 7 (4–NA) 8 35 (12–NA) 69.2% (48.19%, 99.5%), First-line 7 Cetuximab + chemo 71.4% (5/7) 3 — — — — Second-line 9 Cetuximab ± chemo 22% (2/9) 0 6 (3–NA) 5 —