Top Line: Does the addition of cetuximab to adjuvant radiation improve outcomes in patients with intermediate risk head and neck squamous cell carcinoma (HNSCC)?
The Study: Concurrent chemotherapy is standard for patients receiving adjuvant RT for HNSCC with positive margins or extracapsular extension (high risk disease). However, the benefit of concurrent systemic therapy is less certain for patients who don’t meet these criteria but have other risk factors for recurrence. In RTOG 0920, 577 patients with resected HNSCC of the oral cavity, oropharynx, or larynx who had at least one intermediate risk feature were randomized to receive adjuvant RT with or without cetuximab. The risk factors included a close (<5mm) margin, pT3-4a tumor, pN2 disease, PNI or LVI, and pT2 oral cavity tumor with >5mm depth of invasion. Positive margins or ECE were not allowed. The prescription dose was 60 Gy in 30 fractions with an optional boost to 66 Gy for close margins. Most patients had oral cavity primaries (63%), a smoking history (65%), HPV-negative disease (80.2%), and high EGFR expression (84.6%). The primary endpoint of overall survival was not significantly improved with the addition of cetuximab. However, there was a significant improvement in DFS. At 3 years, the rate of locoregional failure was lower with the addition of cetuximab (14.7% v 20.2%). HPV-negative patients appeared to derive greater benefit from cetuximab than HPV-positive patients. The rate of grade 3+ toxicity was higher with cetuxmiab (70.3% v 39.7%), which was mainly driven by skin toxicity. We’ve learned more recently in the definitive setting that cetuximab isn’t as effective as cisplatin but also isn’t really much less toxic. So the question becomes is cetuximab the best systemic agent to improve outcomes in the intermediate population? How might other cytotoxic drugs or regimens compare in efficacy and toxicity to cetuximab?
TBL: In RTOG 0920, the addition of cetuximab to adjuvant radiation for intermediate risk HNSCC significantly improved DFS but not OS. | Machtay, J Clin Oncol 2025
The Study: Concurrent chemotherapy is standard for patients receiving adjuvant RT for HNSCC with positive margins or extracapsular extension (high risk disease). However, the benefit of concurrent systemic therapy is less certain for patients who don’t meet these criteria but have other risk factors for recurrence. In RTOG 0920, 577 patients with resected HNSCC of the oral cavity, oropharynx, or larynx who had at least one intermediate risk feature were randomized to receive adjuvant RT with or without cetuximab. The risk factors included a close (<5mm) margin, pT3-4a tumor, pN2 disease, PNI or LVI, and pT2 oral cavity tumor with >5mm depth of invasion. Positive margins or ECE were not allowed. The prescription dose was 60 Gy in 30 fractions with an optional boost to 66 Gy for close margins. Most patients had oral cavity primaries (63%), a smoking history (65%), HPV-negative disease (80.2%), and high EGFR expression (84.6%). The primary endpoint of overall survival was not significantly improved with the addition of cetuximab. However, there was a significant improvement in DFS. At 3 years, the rate of locoregional failure was lower with the addition of cetuximab (14.7% v 20.2%). HPV-negative patients appeared to derive greater benefit from cetuximab than HPV-positive patients. The rate of grade 3+ toxicity was higher with cetuxmiab (70.3% v 39.7%), which was mainly driven by skin toxicity. We’ve learned more recently in the definitive setting that cetuximab isn’t as effective as cisplatin but also isn’t really much less toxic. So the question becomes is cetuximab the best systemic agent to improve outcomes in the intermediate population? How might other cytotoxic drugs or regimens compare in efficacy and toxicity to cetuximab?
TBL: In RTOG 0920, the addition of cetuximab to adjuvant radiation for intermediate risk HNSCC significantly improved DFS but not OS. | Machtay, J Clin Oncol 2025