The final analysis of the phase 3 GORTEC-REACH study (NCT02999087) reveals that the addition of avelumab (Bavencio) to cetuximab (Erbitux) and radiotherapy demonstrates efficacy in cisplatin-unfit patients with head and neck squamous cell carcinoma (HNSCC), while showing inferior outcomes in cisplatin-eligible patients. The results, presented at the 2024 ESMO Congress, highlight the importance of patient stratification in HNSCC treatment.
Key Findings in Cisplatin-Unfit Patients
In patients deemed unfit for cisplatin, the addition of avelumab to cetuximab plus radiotherapy showed a favorable PFS benefit (adjusted HR, 0.80; 95% CI, 0.60-1.06) and a low distant metastasis rate (subHR, 0.24; 95% CI, 0.11-0.49). The 4-year PFS rate was 33.7% (95% CI, 26.2%-42.2%) with the avelumab regimen compared to 18.4% (95% CI, 12.5%-26.1%) with the standard of care (SOC). The 4-year OS rates were 42.6% (95% CI, 34.3%-51.3%) and 39.4% (95% CI, 30.8%-48.7%) respectively. However, the regimen did not confer superior overall survival (OS) vs the SOC in this population (HR 1.05, 95% CI 0.76-1.44).
Contrasting Outcomes in Cisplatin-Eligible Patients
Conversely, in cisplatin-eligible patients, the study found that avelumab plus cetuximab and radiotherapy led to inferior outcomes compared to the SOC. Specifically, PFS (HR, 1.40; 95% CI, 1.07-1.82; P = .013), loco-regional progression (subHR, 2.26; 95% CI, 1.59-3.22), and OS (HR, 1.43; 95% CI, 1.05-1.93; P = .021) were all worse with the addition of avelumab. The 4-year PFS rates were 42.3% (95% CI, 35.7%-49.2%) with the avelumab regimen versus 54.7% (95% CI, 47.8%-61.4%) with the SOC. The 4-year OS rates were 55.1% (95% CI, 48.3%-61.8%) and 67.1% (95% CI, 60.4%-73.2%) respectively. A potential improvement in the progression of distant metastases was observed (subHR=0.63; 95% CI, 0.32-1.22).
Expert Commentary
Dr. Yungan Tao, a radiation oncologist at the Gustave Roussy Institute and president-elect of GORTEC, presented these findings at ESMO. He highlighted that while the addition of an immune checkpoint inhibitor to cetuximab plus radiotherapy did not improve PFS compared to standard cisplatin-based therapy in the overall patient population, the subgroup analysis revealed a significant difference based on cisplatin eligibility.
These results suggest that avelumab in combination with cetuximab and radiotherapy may offer a valuable treatment option for HNSCC patients who are unable to tolerate cisplatin. However, the regimen is not recommended for cisplatin-eligible patients due to the observed inferior outcomes.
