A pembrolizumab and radiotherapy regime was no better than cetuximab in locally advanced squamous cell carcinoma of the head and neck
Pembrolizumab and radiotherapy failed to improve tumour control and survival compared to a standard of care regime with cetuximab and radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck according to a phase II randomised study by French researchers.
Most head and neck cancers are derived from the mucosal epithelium in the oral cavity, pharynx and larynx and are known collectively as head and neck squamous cell carcinoma. Head and neck cancer is the seventh most common cancer worldwide and accounts for over 800,000 new cases annually.
Pembrolizumab is a monoclonal antibody directed against programmed cell death protein 1 (PD-1) and it has been shown that in combination with platinum and 5-fluorouracil, the drug is an appropriate first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). In addition, pembrolizumab monotherapy is also an appropriate first-line treatment for PD-L1-positive recurrent or metastatic HNSCC. However, while effective as monotherapy, the drug has also been found to significantly increase both the response and outcome in patients with metastatic non-small-cell lung cancer, when combined with radiotherapy. Many patients with HNSCC have locally advanced disease and are commonly managed with cetuximab plus radiotherapy which significantly improves overall survival at 5 years compared with radiotherapy alone, hence confirming the regime as an important treatment option in this group of patients. Nevertheless, the regime is associated with acute and late toxicities, including myelosuppression, severe nausea/vomiting, irreversible renal failure, hearing loss, and neurotoxicity, prompting the need for effective alternatives.
Based on the effectiveness of pembrolizumab and radiation therapy in patients with non-small cell lung cancer, in the present study, the French team tested this combination against cetuximab-radiotherapy in patients with non-operated stage III-IVa-b SCC of oral cavity, oropharynx, hypopharynx and larynx. Patients received once-daily radiotherapy with weekly cetuximab or 200mg Q3W pembrolizumab during RT and the primary endpoint was the loco-regional control (LRC) rate 15 months after radiotherapy.
Pembrolizumab and head and neck squamous cell carcinoma outcomes
A total of 133 patients with a median age was 65 years, 92% of whom were smokers, were randomised to either arm (67 to pembrolizumab) and followed for a median of 25 months.
The 15-month LRC rate was 59% with cetuximab and 60% with pembrolizumab, representing a non-significant difference (Odds ratio, OR = 1.05, 95% CI 0.43 – 2.59, p = 0.91). In addition, there were no significant difference between arms for progression-free survival (Hazard ratio, HR = 0.85, 95% CI 0.55 – 1.32, p = 0.47) or for overall survival (HR = 0.83, 95% CI 0.49 – 1.40, p = 0.49).
Despite the lack of difference in cancer outcomes, toxicity was lower with pembrolizumab than with cetuximab, with 74% vs 92% patients having at least one grade ≥ 3 adverse event (p=0.006) and which were mainly mucositis, radio-dermatitis and rash.
The authors concluded that compared to cetuximab with radiotherapy, pembrolizumab and concomitant radiotherapy, did not improve the tumour control and survival but appeared less toxic in unfit patients with locally, advanced, squamous cell carcinoma of the head and neck.
Toa Y et al. Pembrolizumab versus cetuximab, concurrent with radiotherapy in patients with locally advanced squamous cell carcinoma of head and neck unfit for cisplatin (GORTEC 2015-01 PembroRad): a multicenter, randomized, phase 2 trial. Ann Oncol 2022