Observational Study of the Cetuximab Relative Dose Intensity (RDI) in the First-Line Treatment of Recurrent And/or Metastatic Squamous Cell Carcinoma of the Head and Neck (R/M SCCHN): Data on the Maintenance and Every Two Weeks Use (DIRECT Study)

In EXTREME pivotal Phase III trial, Cetuximab (CTX) associated with chemotherapy (CT) based on platinum (cisplatin or carboplatin) + 5-fluorouracil (5-FU), followed by cetuximab single agent (maintenance) has demonstrated improved survival outcomes compared to CT alone in R/M SCCHN in first-line therapy. DIRECT is the first observational, prospective study evaluating CTX RDI in this setting. Here, we focus on CTX maintenance phase and every two weeks usage (administration frequency at physician discretion). 157 adult patients with R/M SCCHN treated in first-line with CTX according to the scheme of the pivotal study in usual medical practice were included in this national multicenter study (56 centers in France) over two years (Nov 2012-June 2014) and were followed-up during a maximum period of 12 months. 45.8 % (n = 72) of the patients have received CTX maintenance. The median duration of maintenance was 15.8 ± 10.5 weeks (n = 72). 12-month-PFS rate was 23.1% (CI95% [14.0%; 33.5%]). 12-month-OS rate was 70.1% ([57.5%; 79.6%]). For patients with disease free interval less than 6 months (n = 55), 12-month-OS rate was 41.2% ([27.1%; 54.8]). During maintenance, 54.2% (n = 39) of patients have received CTX every two weeks (e2w) administration and 45.8 (n = 33) once a week. 12-month-PFS rate and 12-month-OS rate were not worse in patients with e2w versus weekly administration (weekly, n = 33 vs e2w, n = 39): 18.2% ([7.4% 32.8%]) vs 27.5% ([14.3%; 42.3%]), p = 0.2; 62.6% ([43.6% 76.8%]) vs 77% ([59.1%; 87.8%]), p = 0.2 respectively for PFS and OS rates. Cutaneous toxicities (grade ≥ 3) were observed in 12/157 patients (7.6%). This real life data indicates that CTX maintenance treatment every other week is feasible in R/M SCCHN patients and seems not to result in a reduced efficacy compared with weekly administration. In addition, cutaneous toxicity rate (grade ≥ 3) was similar in the Extreme study.