Background: Achievement of a favorable (> PR) response (particularly CR) at the PTS to IC predicts a higher likelihood of long-term disease control after definitive chemoradiotherapy (CRT) in SCCHN. Low T classification and p16 + oropharynx [OP]SCCHN associate with favorable PTS response to IC. Based on improved tumor response rate with cetuximab added to chemotherapy in the EXTREME trial, we hypothesized a higher PTS CR rate with the addition of cetuximab to APF given as IC before CRT. Methods: Two consecutive prospective phase II trials (APF and APF+Cetux) were performed with the primary objective to determine the response rates (CR, PR, <PR) at the PTS. 30 patients were treated with APF (weekly nab-paclitaxel 100 mg/m² and every 3 week cisplatin 75 mg/m² and 5-FU 750 mg/m²/dayx3) and 30 patients were treated with APF+Cetux (APF + weekly cetuximab 250 mg/m²). After two cycles of IC, PTS response assessment by clinical exam was performed by experienced oncologic otolaryngologists. Patients were then scheduled for a third cycle of IC followed by definitive CRT (with cisplatin). Results: After two cycles of APF or APF+Cetux, CR rates at the PTS were 76.7% (23 patients) and 53% (16 patients), respectively. PR and <PR rates at the PTS after two cycles of APF were 16.7% (5 patients) and 6.7% (2 patients) and after APF+Cetux were 47% (14 patients) and 0%, respectively. CR rates at the PTS were consistently higher with APF compared to APF+Cetux when stratified for T classification and p16 status (Table). Conclusions: Unexpectedly, the addition of cetuximab to APF did not increase the CR rate at the PTS even when stratified for T classification and p16 status. This observation is consistent with our historical experience of TPF+Cetux (Adkins et al ASCO 2011 #5560). Validation of these findings in a randomized trial is indicated. Clinical trial information: NCT01566435 AND NCT00736944.

* p16 not performed in 1.